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Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram commented on gene: RCAN1: As reviewed by Zornitza Stark, whole-genome sequencing performed on 320 individuals from 201 families with familial and sporadic nephrotic syndrome (NS)/ focal segmental glomerulosclerosis (FSGS) identified two variants in RCAN1 gene in two families with autosomal dominant FSGS/ steroid-resistant nephrotic syndrome (SRNS). In addition, there is some functional data available.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.

This gene can be rated amber with current evidence.
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Classified gene: RCAN1 as Amber List (moderate evidence)
Proteinuric renal disease v4.12 RCAN1 Achchuthan Shanmugasundram Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.11 RCAN1 Achchuthan Shanmugasundram Phenotypes for gene: RCAN1 were changed from FSGS; proteinuria to focal segmental glomerulosclerosis, MONDO:0100313; nephrotic syndrome, MONDO:0005377
Proteinuric renal disease v4.10 RCAN1 Achchuthan Shanmugasundram reviewed gene: RCAN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: focal segmental glomerulosclerosis, MONDO:0100313, nephrotic syndrome, MONDO:0005377; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Classified gene: PRDM15 as Amber List (moderate evidence)
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated individuals with three different biallelic variants, mouse and Xenopus models and functional data) for the promotion of this gene to green rating in the next GMS update.
Proteinuric renal disease v4.10 PRDM15 Achchuthan Shanmugasundram Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.9 PRDM15 Achchuthan Shanmugasundram Phenotypes for gene: PRDM15 were changed from Steroid resistant nephrotic syndrome; Holoprosencephaly to steroid-resistant nephrotic syndrome, MONDO:0044765
Proteinuric renal disease v4.8 PRDM15 Achchuthan Shanmugasundram Publications for gene: PRDM15 were set to 31950080
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PRDM15.
Proteinuric renal disease v4.7 PRDM15 Achchuthan Shanmugasundram reviewed gene: PRDM15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33593823; Phenotypes: steroid-resistant nephrotic syndrome, MONDO:0044765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v4.7 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia #242900 to Schimke immunoosseous dysplasia, OMIM:242900
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Classified gene: NOS1AP as Amber List (moderate evidence)
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark and reported in PMID:33523862, there are two unrelated individuals with homozygous NOS1AP variants (c.428G>A/ p.Cys143Tyr & c.345-3T-G) and presenting with nephrotic syndrome, type 22 (MIM# 619155).

Introduction of patient variant (c.428G>A) has resulted in aberrant glomeruli formation in kidney organoids. In addition, homozygous exon 3-deleted mice recapitulated the human phenotype, exhibiting proteinuria, foot process effacement, and glomerulosclerosis.

Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Proteinuric renal disease v4.6 NOS1AP Achchuthan Shanmugasundram Gene: nos1ap has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v4.5 NOS1AP Achchuthan Shanmugasundram Phenotypes for gene: NOS1AP were changed from Nephrotic syndrome, type 22, MIM# 619155 to Nephrotic syndrome, type 22, OMIM:619155
Proteinuric renal disease v4.4 NOS1AP Achchuthan Shanmugasundram Publications for gene: NOS1AP were set to
Proteinuric renal disease v4.3 NOS1AP Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: NOS1AP.
Proteinuric renal disease v4.3 NOS1AP Achchuthan Shanmugasundram reviewed gene: NOS1AP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33523862; Phenotypes: Nephrotic syndrome, type 22, OMIM:619155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v4.1 FN1 Eleanor Williams commented on gene: FN1: Looking at reports of End-stage renal disease and the age of onset:

PMID: 18268355 - Castelletti et al 2008 - 3 members of the same extended family are reported to have ESRF at ages 74, 32 and 34.
PMID: 27056061- Ohtsubo et al 2016 - 1 patient with ESRD at 34 years, and one other at age 49.
PMID: 31419955 - Gonçalves Dos Reis Monteiro et al 2019 - the father and son reported do not appear to have ESRD.
Proteinuric renal disease v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Proteinuric renal disease v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Proteinuric renal disease v3.3 GLA Sarah Leigh Tag Q3_22_rating was removed from gene: GLA.
Tag Q3_22_NHS_review was removed from gene: GLA.
Proteinuric renal disease v3.3 EMP2 Sarah Leigh Tag Q2_22_rating was removed from gene: EMP2.
Tag Q2_22_expert_review was removed from gene: EMP2.
Proteinuric renal disease v3.3 GLA Sarah Leigh reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v3.3 EMP2 Sarah Leigh reviewed gene: EMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v3.2 GLA Sarah Leigh Source Expert Review Green was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v3.2 EMP2 Sarah Leigh Source Expert Review Amber was added to EMP2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Proteinuric renal disease v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Proteinuric renal disease v3.0 Eleanor Williams promoted panel to version 3.0
Proteinuric renal disease v2.77 EMP2 Eleanor Williams Tag Q2_22_expert_review tag was added to gene: EMP2.
Proteinuric renal disease v2.77 GLA Eleanor Williams Classified gene: GLA as Amber List (moderate evidence)
Proteinuric renal disease v2.77 GLA Eleanor Williams Added comment: Comment on list classification: Following review by an NHS expert, this gene is recommended to be rated as Green following GMS review.
Proteinuric renal disease v2.77 GLA Eleanor Williams Gene: gla has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.76 GLA Eleanor Williams Tag Q3_22_rating tag was added to gene: GLA.
Tag Q3_22_NHS_review tag was added to gene: GLA.
Proteinuric renal disease v2.76 GLA John Sayer reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33928440, PMID: 33437642; Phenotypes: Proteinuria, albuminuria, end stage kidney disease, cardiomyopathy, stroke; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v2.76 EMP2 Eleanor Williams Classified gene: EMP2 as Green List (high evidence)
Proteinuric renal disease v2.76 EMP2 Eleanor Williams Added comment: Comment on list classification: The rating of this gene has been left as green, but with a recommendation for demotion to amber following expert review of the evidence.
Proteinuric renal disease v2.76 EMP2 Eleanor Williams Gene: emp2 has been classified as Green List (High Evidence).
Proteinuric renal disease v2.75 EMP2 Eleanor Williams Tag Q2_22_rating tag was added to gene: EMP2.
Proteinuric renal disease v2.75 PODXL Eleanor Williams Tag gene-checked tag was added to gene: PODXL.
Proteinuric renal disease v2.75 TBC1D8B Eleanor Williams Tag gene-checked tag was added to gene: TBC1D8B.
Proteinuric renal disease v2.75 TNS2 Eleanor Williams Tag gene-checked tag was added to gene: TNS2.
Proteinuric renal disease v2.75 ITSN1 Arina Puzriakova Tag gene-checked tag was added to gene: ITSN1.
Proteinuric renal disease v2.75 FAT1 Arina Puzriakova Tag gene-checked tag was added to gene: FAT1.
Proteinuric renal disease v2.75 TRIM8 Eleanor Williams Tag Q4_21_rating was removed from gene: TRIM8.
Proteinuric renal disease v2.75 LCAT Eleanor Williams Tag Q4_21_rating was removed from gene: LCAT.
Tag Q4_21_NHS_review was removed from gene: LCAT.
Proteinuric renal disease v2.75 TRIM8 Eleanor Williams commented on gene: TRIM8
Proteinuric renal disease v2.75 LCAT Eleanor Williams commented on gene: LCAT: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.74 TRIM8 Eleanor Williams Source Expert Review Green was added to TRIM8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.74 LCAT Eleanor Williams Source Expert Review Green was added to LCAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.73 YRDC Eleanor Williams Phenotypes for gene: YRDC were changed from Galloway-Mowat syndrome to Galloway-Mowat syndrome MONDO:0009627
Proteinuric renal disease v2.72 YRDC Eleanor Williams Tag for-review was removed from gene: YRDC.
Proteinuric renal disease v2.72 GON7 Eleanor Williams Tag for-review was removed from gene: GON7.
Proteinuric renal disease v2.72 APOL1 Eleanor Williams Mode of pathogenicity for gene: APOL1 was changed from to Other
Proteinuric renal disease v2.71 APOL1 Eleanor Williams Tag for-review was removed from gene: APOL1.
Proteinuric renal disease v2.71 DAAM2 Eleanor Williams Tag for-review was removed from gene: DAAM2.
Proteinuric renal disease v2.71 FN1 Eleanor Williams Phenotypes for gene: FN1 were changed from Glomerulopathy with fibronectin deposits 2, 601894 to Glomerulopathy with fibronectin deposits 2, OMIM:601894
Proteinuric renal disease v2.70 FN1 Eleanor Williams Tag for-review was removed from gene: FN1.
Proteinuric renal disease v2.70 APOE Eleanor Williams Phenotypes for gene: APOE were changed from Lipoprotein glomerulopathy, MIM# 611771 to Lipoprotein glomerulopathy, OMIM:611771
Proteinuric renal disease v2.69 APOE Eleanor Williams Tag for-review was removed from gene: APOE.
Proteinuric renal disease v2.69 TPRKB Eleanor Williams Phenotypes for gene: TPRKB were changed from Galloway-Mowat syndrome 5 #617731 to Galloway-Mowat syndrome 5, OMIM:617731
Proteinuric renal disease v2.68 TPRKB Eleanor Williams Tag for-review was removed from gene: TPRKB.
Proteinuric renal disease v2.68 CD151 Eleanor Williams Tag for-review was removed from gene: CD151.
Tag Q3_21_NHS_review was removed from gene: CD151.
Proteinuric renal disease v2.68 DGKE Eleanor Williams Phenotypes for gene: DGKE were changed from Nephrotic syndrome, type 7 #615008 to Nephrotic syndrome, type 7, OMIM:615008
Proteinuric renal disease v2.67 DGKE Eleanor Williams Tag for-review was removed from gene: DGKE.
Proteinuric renal disease v2.67 AMN Eleanor Williams Phenotypes for gene: AMN were changed from Megaloblastic anemia-1, Norwegian type, 261100; (originally on the Imerslund-Grasbeck syndrome gene panel) to Megaloblastic anemia-1, Norwegian type, OMIM:261100
Proteinuric renal disease v2.66 AMN Eleanor Williams Tag for-review was removed from gene: AMN.
Proteinuric renal disease v2.66 YRDC Eleanor Williams commented on gene: YRDC: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 GON7 Eleanor Williams commented on gene: GON7: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 APOL1 Eleanor Williams commented on gene: APOL1: After NHSGenomic Medicine Service consideration, the rating of this gene has not been changed.
Proteinuric renal disease v2.66 DAAM2 Eleanor Williams commented on gene: DAAM2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 FN1 Eleanor Williams commented on gene: FN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 APOE Eleanor Williams commented on gene: APOE: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 TPRKB Eleanor Williams commented on gene: TPRKB: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 CD151 Eleanor Williams commented on gene: CD151: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Proteinuric renal disease v2.66 DGKE Eleanor Williams commented on gene: DGKE: The rating of this gene has been updated following NHS Genomic Medicine Service approval. The reviewers note and overlap with aHUS
Proteinuric renal disease v2.66 AMN Eleanor Williams commented on gene: AMN: The rating of this gene has been updated following NHS Genomic Medicine Service approval. The reviewers note that a homozygous splice variant in patient with Imerslund-Grasbeck syndrome has been reported.
Proteinuric renal disease v2.65 YRDC Eleanor Williams Source Expert Review Green was added to YRDC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 GON7 Eleanor Williams Source Expert Review Green was added to GON7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 DAAM2 Eleanor Williams Source Expert Review Green was added to DAAM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 FN1 Eleanor Williams Source Expert Review Green was added to FN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 APOE Eleanor Williams Source Expert Review Green was added to APOE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 TPRKB Eleanor Williams Source Expert Review Green was added to TPRKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 CD151 Eleanor Williams Source Expert Review Green was added to CD151.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 DGKE Eleanor Williams Source Expert Review Green was added to DGKE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.65 AMN Eleanor Williams Source Expert Review Green was added to AMN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v2.64 EMP2 Daniel Gale reviewed gene: EMP2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31508419, 24814193, 29058154; Phenotypes: Proteinuric renal disease, Unexplained paediatric onset end-stage renal disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.64 NLRP3 Arina Puzriakova Mode of inheritance for gene: NLRP3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuric renal disease v2.63 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from SRNS to Muckle-Wells syndrome, OMIM:191900; Renal amyloidosis
Proteinuric renal disease v2.62 MEFV Arina Puzriakova Phenotypes for gene: MEFV were changed from Familial Mediterranean fever, AR #249100 to Familial Mediterranean fever, AD, OMIM:134610; Familial Mediterranean fever, AR, OMIM:249100
Proteinuric renal disease v2.61 LCAT Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: LCAT.
Proteinuric renal disease v2.61 COL4A4 Arina Puzriakova Phenotypes for gene: COL4A4 were changed from to Alport syndrome 2, autosomal recessive, OMIM:203780; Hematuria,familial benign, OMIM:141200
Proteinuric renal disease v2.60 TRIM8 Ivone Leong Classified gene: TRIM8 as Amber List (moderate evidence)
Proteinuric renal disease v2.60 TRIM8 Ivone Leong Gene: trim8 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.59 TRIM8 Ivone Leong Tag Q4_21_rating tag was added to gene: TRIM8.
Proteinuric renal disease v2.59 TRIM8 Ivone Leong changed review comment from: Comment on list classification: New gene added by Julia Baptista (Royal Devon and Exeter NHS Foundation Trust). This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.; to: Comment on list classification: New gene added by Julia Baptista (Royal Devon and Exeter NHS Foundation Trust). This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Proteinuric renal disease v2.59 TRIM8 Ivone Leong Entity copied from Unexplained kidney failure in young people v1.97
Proteinuric renal disease v2.59 TRIM8 Ivone Leong gene: TRIM8 was added
gene: TRIM8 was added to Proteinuric renal disease. Sources: Expert Review Green,Literature
Mode of inheritance for gene: TRIM8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM8 were set to 33508234; 32531461; 32193649; 33508234
Phenotypes for gene: TRIM8 were set to nephrotic syndrome; epilepsy; Focal segmental glomerulosclerosis and neurodevelopmental syndrome, OMIM:619428
Mode of pathogenicity for gene: TRIM8 was set to Other
Proteinuric renal disease v2.58 LCAT Eleanor Williams Classified gene: LCAT as Amber List (moderate evidence)
Proteinuric renal disease v2.58 LCAT Eleanor Williams Added comment: Comment on list classification: Leaving rating as amber for now, but with a green rating recommendation following GMS review. There are several reported cases where proteinuria is a prominent feature, plus a green expert review reporting a case of a family presenting with proteinuric kidney disease
Proteinuric renal disease v2.58 LCAT Eleanor Williams Gene: lcat has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.57 LCAT Eleanor Williams Phenotypes for gene: LCAT were changed from Norum disease #245900 to Norum disease, OMIM:245900; Norum disease, MONDO:0009515; LCAT DEFICIENCY
Proteinuric renal disease v2.56 LCAT Eleanor Williams Publications for gene: LCAT were set to 6078131
Proteinuric renal disease v2.55 LCAT Eleanor Williams edited their review of gene: LCAT: Changed publications to: 21315357, 30201532, 29535099, 22108153, 28508023, 25657982, 9884427
Proteinuric renal disease v2.55 LCAT Eleanor Williams Tag Q4_21_rating tag was added to gene: LCAT.
Proteinuric renal disease v2.55 LCAT Eleanor Williams edited their review of gene: LCAT: Added comment: Several cases in which proteinuria was noted in patients with LCAT deficiency are reported, including:

PMID: 21315357 - Holleboom et al 2011 - report 3 siblings (age 17, 12 and 3 years) in a family with HDL deficency. The 17-year-old was referred for renal pathology compatible with a metabolic disorder, including FLD. Corneal opacification and proteinuria were observed in all three and they were found to be homozygous for a missense variant in LCAT which disrupted the second disulfide. LCAT protein and activity were undetectable in the patients' plasma. The parents and an unaffected brother were heterozygous for the variant.

PMID: 30201532 - Hanna et al 2018 - report a 29-year-old female who initially presented with discomfort, photophobia, and decreased vision in both eyes. Bilateral corneal clouding, severely reduced HDL cholesterol, and proteinuria were noted. Two heterozygous mutations of the LCAT gene were identified: c.321C>A (p.Tyr107 *) and c.1034C>T (p.Thr345Met)

PMID: 29535099 - Morales et al 2018 - report 44-year-old woman diagnosed with corneal dystrophy and anaemia. Analysis showed proteinuria between 1 and 2 g/day. A missense homozygous variant in the LCAT gene c.368G>C (p (R123p)) was identified.

PMID: 22108153 - Roshan et al 2011 - report a 50-year-old man with uncontrolled hypertension, hemolytic anemia, and renal insufficiency. He had a long history of proteinuria (3+ for at least 30 years). He was found to have diffuse marked corneal opacification. Sequencing the LCAT gene showed a homozygous missense mutation. His parents were first cousins.


Cases presenting with proteinuria with a LCAT deficiency diagnosis but no molecular analyses:

PMID: 28508023 - Balwani et al 2016 - a patient with nephrotic syndrome, which renal biopsy revealed classic features of LCAT deficiency. There was no obvious family history and the patient was without any corneal deposits and normal HDL-C levels. NOTE NO MOLECULAR DIAGNOSIS.

PMID: 25657982 - Mahdi Althaf et al 2015 - 30-year-old male was referred for persistent proteinuria. Bilateral corneal ring opacities were noted. Renal biopsy findings were consistent with LCAT deficiency.; Changed phenotypes to: Norum disease, OMIM:245900, Norum disease, MONDO:0009515, LCAT DEFICIENCY
Proteinuric renal disease v2.55 CD151 Eleanor Williams Tag Q3_21_NHS_review tag was added to gene: CD151.
Proteinuric renal disease v2.55 CD151 Eleanor Williams Classified gene: CD151 as Amber List (moderate evidence)
Proteinuric renal disease v2.55 CD151 Eleanor Williams Added comment: Comment on list classification: Further case reported by Natalie Forrester from the South West Genomic Laboratory Hub, which supports the recommendation for a green rating.
Proteinuric renal disease v2.55 CD151 Eleanor Williams Gene: cd151 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.54 CD151 Eleanor Williams Publications for gene: CD151 were set to 15265795; 17015618; 29138120
Proteinuric renal disease v2.53 CD151 Eleanor Williams Phenotypes for gene: CD151 were changed from Nephropathy with pretibial epidermolysis bullosa and deafness #609057 to Nephropathy with pretibial epidermolysis bullosa and deafness, OMIM:609057; nephrotic syndrome - deafness - pretibial epidermolysis bullosa syndrome, MONDO:0012190
Proteinuric renal disease v2.52 COQ2 Ivone Leong Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1 #607426 to Coenzyme Q10 deficiency, primary, 1, OMIM:607426
Proteinuric renal disease v2.51 TBC1D8B Ivone Leong Added comment: Comment on phenotypes: Previously:
Steroid-resistant nephrotic syndrome
Proteinuric renal disease v2.51 TBC1D8B Ivone Leong Phenotypes for gene: TBC1D8B were changed from Steroid-resistant nephrotic syndrome to Nephrotic syndrome, type 20, OMIM:301028
Proteinuric renal disease v2.50 CD151 Natalie Forrester reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15265795, 29138120, 17015618, 32641585, 22338088, 18787104, 22201679; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness #609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.50 RCAN1 Zornitza Stark gene: RCAN1 was added
gene: RCAN1 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: RCAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RCAN1 were set to 33863784
Phenotypes for gene: RCAN1 were set to FSGS; proteinuria
Review for gene: RCAN1 was set to AMBER
Added comment: Two families reported, some functional data.
Sources: Literature
Proteinuric renal disease v2.50 PRDM15 Zornitza Stark gene: PRDM15 was added
gene: PRDM15 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080
Phenotypes for gene: PRDM15 were set to Steroid resistant nephrotic syndrome; Holoprosencephaly
Review for gene: PRDM15 was set to AMBER
Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic SRNS including HPE, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data focused on the brain phenotype. Two additional homozygous missense identified with isolated SRNS.
Sources: Literature
Proteinuric renal disease v2.50 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from LOWE OCULOCEREBRORENAL SYNDROME #309000; Dent disease 2 #300555 to Lowe syndrome, OMIM:309000; Dent disease 2, OMIM:300555
Proteinuric renal disease v2.49 OCRL Eleanor Williams commented on gene: OCRL: Genotype/Phenotype information: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.
Proteinuric renal disease v2.49 APOL1 Eleanor Williams Publications for gene: APOL1 were set to 20647424; 23766536
Proteinuric renal disease v2.48 APOL1 Eleanor Williams edited their review of gene: APOL1: Added comment: PMID: 33517446 - Ge et al 2021 - demonstrate a mouse model to study APOL1 risk variants associated susceptibility to NFAT-mediated FSGS. They provide evidence that APOL1 G1 induced glomerular lipid accumulation correlates with loss of renal function and confirm that APOL1 G1/G2 risk variant is associated with mitochondrial dysfunction.; Changed publications: 33517446
Proteinuric renal disease v2.48 LCAT Ania Koziell reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: None; Publications: Muthusethupathi MA, Padmanabhan R, Date A, Jayakumar M, Rajendran S, Vijayakumar R. Familial Lecithin:cholesterol acyltransferase deficiency with renal failure in two siblings. First case report from India. Nephron. 1999 Jan, 81(1):89-93. doi: 10.1159/000045253. PMID: 9884427.; Phenotypes: proteinuric renal disease, pseudo-membranous nephropathy, unexplained renal failure in young adults; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Classified gene: APOL1 as Amber List (moderate evidence)
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to amber, following review and proposal for green by Natalie Forrester. It should be considered for green rating following GMS review.
Proteinuric renal disease v2.48 APOL1 Eleanor Williams Gene: apol1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.47 APOL1 Eleanor Williams Phenotypes for gene: APOL1 were changed from Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551 to {Focal Segmental Glomerulosclerosis 4, Susceptibility to} OMIM:612551; {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551
Proteinuric renal disease v2.46 APOL1 Eleanor Williams Mode of inheritance for gene: APOL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.45 APOL1 Eleanor Williams Publications for gene: APOL1 were set to 20647424
Proteinuric renal disease v2.44 APOL1 Eleanor Williams Tag for-review tag was added to gene: APOL1.
Proteinuric renal disease v2.44 NOS1AP Zornitza Stark gene: NOS1AP was added
gene: NOS1AP was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: NOS1AP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NOS1AP were set to Nephrotic syndrome, type 22, MIM# 619155
Review for gene: NOS1AP was set to GREEN
gene: NOS1AP was marked as current diagnostic
Added comment: Nephrotic syndrome type 22 (NPHS22) is an autosomal recessive renal disease characterized by onset of progressive kidney dysfunction in infancy. Affected individuals usually present with edema associated with hypoproteinemia, proteinuria, and microscopic hematuria. Renal biopsy shows effacement of the podocyte foot processes, glomerulosclerosis, and thickening of the glomerular basement membrane. The disease is steroid-resistant and progressive, resulting in end-stage renal disease usually necessitating kidney transplant. Two unrelated families and animal model.

No PMID yet: https://advances.sciencemag.org/content/7/1/eabe1386
Sources: Literature
Proteinuric renal disease v2.44 APOL1 Natalie Forrester reviewed gene: APOL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23766536; Phenotypes: chronic kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.44 GON7 Eleanor Williams Tag for-reivew was removed from gene: GON7.
Tag for-review tag was added to gene: GON7.
Proteinuric renal disease v2.44 YRDC Eleanor Williams Classified gene: YRDC as Amber List (moderate evidence)
Proteinuric renal disease v2.44 YRDC Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, based on 2 cases plus some functional data. At the next GMS review it could be considered for green rating based on the external expert review.
Proteinuric renal disease v2.44 YRDC Eleanor Williams Gene: yrdc has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.43 YRDC Eleanor Williams Tag for-review tag was added to gene: YRDC.
Proteinuric renal disease v2.43 GON7 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber, based on 4 related cases (founder effect) plus one other case plus some functional data. At the next GMS review it should be considered for green rating based on the external expert review.; to: Comment on list classification: Promoting from grey to amber, based on 4 related cases (founder effect) plus one other case plus some functional data. At the next GMS review it could be considered for green rating based on the external expert review.
Proteinuric renal disease v2.43 YRDC Eleanor Williams reviewed gene: YRDC: Rating: AMBER; Mode of pathogenicity: None; Publications: 31481669; Phenotypes: Galloway-Mowat syndrome MONDO:0009627; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.43 GON7 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber, based on 2 cases plus some functional data. At the next GMS review it should be considered for green rating based on the external expert review.; to: Comment on list classification: Promoting from grey to amber, based on 4 related cases (founder effect) plus one other case plus some functional data. At the next GMS review it should be considered for green rating based on the external expert review.
Proteinuric renal disease v2.43 GON7 Eleanor Williams Classified gene: GON7 as Amber List (moderate evidence)
Proteinuric renal disease v2.43 GON7 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, based on 2 cases plus some functional data. At the next GMS review it should be considered for green rating based on the external expert review.
Proteinuric renal disease v2.43 GON7 Eleanor Williams Gene: gon7 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.42 GON7 Eleanor Williams Phenotypes for gene: GON7 were changed from Galloway-Mowat syndrome to Galloway-Mowat syndrome MONDO:0009627
Proteinuric renal disease v2.41 GON7 Eleanor Williams Tag founder-effect tag was added to gene: GON7.
Tag for-reivew tag was added to gene: GON7.
Proteinuric renal disease v2.41 GON7 Eleanor Williams reviewed gene: GON7: Rating: AMBER; Mode of pathogenicity: None; Publications: 31481669; Phenotypes: Galloway-Mowat syndrome MONDO:0009627; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.41 KIRREL1 Eleanor Williams Classified gene: KIRREL1 as Amber List (moderate evidence)
Proteinuric renal disease v2.41 KIRREL1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber. 2 cases plus some limited functional data.
Proteinuric renal disease v2.41 KIRREL1 Eleanor Williams Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.40 KIRREL1 Eleanor Williams Phenotypes for gene: KIRREL1 were changed from Steroid-resistant nephrotic syndrome to steroid-resistant nephrotic syndrome MONDO:0044765
Proteinuric renal disease v2.39 KIRREL1 Eleanor Williams reviewed gene: KIRREL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31472902; Phenotypes: steroid-resistant nephrotic syndrome MONDO:0044765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.39 DAAM2 Eleanor Williams Classified gene: DAAM2 as Amber List (moderate evidence)
Proteinuric renal disease v2.39 DAAM2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, with the recommendation of a green rating following GMS review. 4 unrelated cases, with different variants in DAAM2 in patients with steroid-resistant nephrotic syndrome.
Proteinuric renal disease v2.39 DAAM2 Eleanor Williams Gene: daam2 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.38 DAAM2 Eleanor Williams Deleted their comment
Proteinuric renal disease v2.38 DAAM2 Eleanor Williams Tag for-review tag was added to gene: DAAM2.
Proteinuric renal disease v2.38 DAAM2 Eleanor Williams Classified gene: DAAM2 as Amber List (moderate evidence)
Proteinuric renal disease v2.38 DAAM2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, with the recommendation of a green rating following GMS review. 4 unrelated cases, with different variants in DAAM2 in patients with steroid-resistant nephrotic syndrome.
Proteinuric renal disease v2.38 DAAM2 Eleanor Williams Gene: daam2 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.37 DAAM2 Eleanor Williams Phenotypes for gene: DAAM2 were changed from Steroid-resistant nephrotic syndrome (SRNS) to steroid-resistant nephrotic syndrome MONDO:0044765
Proteinuric renal disease v2.36 IL1RAP Eleanor Williams Classified gene: IL1RAP as Red List (low evidence)
Proteinuric renal disease v2.36 IL1RAP Eleanor Williams Added comment: Comment on list classification: Promoting from grey to red based on expert review reporting one case.
Proteinuric renal disease v2.36 IL1RAP Eleanor Williams Gene: il1rap has been classified as Red List (Low Evidence).
Proteinuric renal disease v2.35 NOP10 Eleanor Williams Classified gene: NOP10 as Red List (low evidence)
Proteinuric renal disease v2.35 NOP10 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to red as there is one reported family with a missense variant in this gene and a phenotype that includes nephrotic syndrome.
Proteinuric renal disease v2.35 NOP10 Eleanor Williams Gene: nop10 has been classified as Red List (Low Evidence).
Proteinuric renal disease v2.34 NOP10 Eleanor Williams reviewed gene: NOP10: Rating: RED; Mode of pathogenicity: None; Publications: 32554502; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.34 DKC1 Eleanor Williams changed review comment from: Variants in this gene have previously been associated with dyskeratosis congenita (bone marrow failure) characterized by telomere attrition. https://omim.org/entry/300126

As reported by expert reviewer PMID: 32554502 - Balogh et al 2020 - reports a large pedigree in which 6 affected males presented with an infantile-onset disorder characterized by steroid-resistant nephrotic syndrome, cataracts (prior to steroid treatment), sensorineural deafness, and enterocolitis and died in early childhood. Using linkage analysis they identified a point mutation in DKC1 (c.616 G>A, p.Glu206Lys) that segregated with the disease in generation II. The variant is absent from gnomAD.; to: Variants in this gene have previously been associated with dyskeratosis congenita (bone marrow failure) characterized by telomere attrition. https://omim.org/entry/300126

As reported by expert reviewer PMID: 32554502 - Balogh et al 2020 - reports a large pedigree in which 6 affected males presented with an infantile-onset disorder characterized by steroid-resistant nephrotic syndrome, cataracts (prior to steroid treatment), sensorineural deafness, and enterocolitis and died in early childhood. Using linkage analysis they identified a point mutation in DKC1 (c.616 G>A, p.Glu206Lys) that segregated with the disease in generation II. The variant is absent from gnomAD. An affected female was found to have skewed x-inactivation.
Proteinuric renal disease v2.34 DKC1 Eleanor Williams Classified gene: DKC1 as Red List (low evidence)
Proteinuric renal disease v2.34 DKC1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to red as there is one reported family with a missense variant in this gene and a phenotype that includes nephrotic syndrome.
Proteinuric renal disease v2.34 DKC1 Eleanor Williams Gene: dkc1 has been classified as Red List (Low Evidence).
Proteinuric renal disease v2.33 DKC1 Eleanor Williams reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: None; Publications: 32554502; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuric renal disease v2.33 DAAM2 Zornitza Stark gene: DAAM2 was added
gene: DAAM2 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: DAAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAAM2 were set to 33232676
Phenotypes for gene: DAAM2 were set to Steroid-resistant nephrotic syndrome (SRNS)
Review for gene: DAAM2 was set to GREEN
Added comment: - steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis on histologic analysis of kidney biopsies and foot process effacement shown by electron microscopy (authors have suggested the term nephrotic syndrome type 22 (NPHS22))
- 4 unrelated families, 3 of which were consanguineous
- 4 unique missense and 1 stop
- in vitro studies for the missense variants
Sources: Literature
Proteinuric renal disease v2.33 NOP10 Moin Saleem gene: NOP10 was added
gene: NOP10 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: NOP10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NOP10 were set to 32554502
Phenotypes for gene: NOP10 were set to steroid-resistant 6 nephrotic syndrome; cataracts (prior to steroid treatment); sensorineural deafness; enterocolitis
Penetrance for gene: NOP10 were set to unknown
Review for gene: NOP10 was set to RED
Added comment: 2 affected females in one pedigree
Sources: Literature
Proteinuric renal disease v2.33 DKC1 Moin Saleem gene: DKC1 was added
gene: DKC1 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DKC1 were set to 32554502
Phenotypes for gene: DKC1 were set to steroid-resistant 6 nephrotic syndrome; cataracts (prior to steroid treatment); sensorineural deafness; enterocolitis
Penetrance for gene: DKC1 were set to unknown
Review for gene: DKC1 was set to RED
Added comment: six affected males in one pedigree
Sources: Literature
Proteinuric renal disease v2.33 KIRREL1 Zornitza Stark gene: KIRREL1 was added
gene: KIRREL1 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIRREL1 were set to 31472902
Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome
Review for gene: KIRREL1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature
Proteinuric renal disease v2.33 Catherine Snow Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Panel version has been signed off
Proteinuric renal disease v2.32 TPRKB Catherine Snow Classified gene: TPRKB as Amber List (moderate evidence)
Proteinuric renal disease v2.32 TPRKB Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.32 TPRKB Catherine Snow Gene: tprkb has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.31 FN1 Catherine Snow Classified gene: FN1 as Amber List (moderate evidence)
Proteinuric renal disease v2.31 FN1 Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.31 FN1 Catherine Snow Gene: fn1 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.30 DGKE Catherine Snow Classified gene: DGKE as Amber List (moderate evidence)
Proteinuric renal disease v2.30 DGKE Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.30 DGKE Catherine Snow Gene: dgke has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.29 CD151 Catherine Snow Classified gene: CD151 as Amber List (moderate evidence)
Proteinuric renal disease v2.29 CD151 Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.29 CD151 Catherine Snow Gene: cd151 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.28 APOE Catherine Snow Classified gene: APOE as Amber List (moderate evidence)
Proteinuric renal disease v2.28 APOE Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.28 APOE Catherine Snow Gene: apoe has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.27 AMN Catherine Snow Classified gene: AMN as Amber List (moderate evidence)
Proteinuric renal disease v2.27 AMN Catherine Snow Added comment: Comment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.
Proteinuric renal disease v2.27 AMN Catherine Snow Gene: amn has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.26 IL1RAP Zornitza Stark gene: IL1RAP was added
gene: IL1RAP was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: IL1RAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RAP were set to 31954058
Phenotypes for gene: IL1RAP were set to Steroid-sensitive nephrotic syndrome
Review for gene: IL1RAP was set to RED
Added comment: A pair of siblings with compound heterozygous variants in this gene and steroid-sensitive nephrotic syndrome. Functional effect of variants demonstrated but mouse model does not have proteinuria.
Sources: Literature
Proteinuric renal disease v2.26 YRDC Zornitza Stark gene: YRDC was added
gene: YRDC was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YRDC were set to 31481669
Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome
Review for gene: YRDC was set to GREEN
gene: YRDC was marked as current diagnostic
Added comment: Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Literature
Proteinuric renal disease v2.26 GON7 Zornitza Stark gene: GON7 was added
gene: GON7 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON7 were set to 31481669
Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome
Review for gene: GON7 was set to GREEN
gene: GON7 was marked as current diagnostic
Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect. Clinical features included proteinuria, microcephaly, brain malformations and developmental delay. Supportive functional data.
Sources: Literature
Proteinuric renal disease v2.26 TPRKB Eleanor Williams Tag for-review tag was added to gene: TPRKB.
Proteinuric renal disease v2.26 CD151 Eleanor Williams Tag for-review tag was added to gene: CD151.
Proteinuric renal disease v2.26 AMN Eleanor Williams Tag for-review tag was added to gene: AMN.
Proteinuric renal disease v2.26 APOE Eleanor Williams Tag for-review tag was added to gene: APOE.
Proteinuric renal disease v2.26 DGKE Eleanor Williams Tag for-review tag was added to gene: DGKE.
Proteinuric renal disease v2.26 FN1 Eleanor Williams Phenotypes for gene: FN1 were changed from Glomerulopathy with fibronectin deposits 2, MIM# 601894 to Glomerulopathy with fibronectin deposits 2, 601894
Proteinuric renal disease v2.25 FN1 Eleanor Williams Publications for gene: FN1 were set to 18268355
Proteinuric renal disease v2.24 FN1 Eleanor Williams Classified gene: FN1 as Green List (high evidence)
Proteinuric renal disease v2.24 FN1 Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to green. More than 3 unrelated cases with FN1 variants reported in patients with Glomerulopathy with Fibronectin Deposits, which has proteinuria as a feature.
Proteinuric renal disease v2.24 FN1 Eleanor Williams Gene: fn1 has been classified as Green List (High Evidence).
Proteinuric renal disease v2.23 FN1 Eleanor Williams Tag for-review tag was added to gene: FN1.
Proteinuric renal disease v2.23 FN1 Eleanor Williams reviewed gene: FN1: Rating: ; Mode of pathogenicity: None; Publications: 18268355, 27056061, 31419955; Phenotypes: Glomerulopathy with Fibronectin Deposits 2, 601894; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuric renal disease v2.23 CD151 Eleanor Williams changed review comment from: Associated with Nephropathy with pretibial epidermolysis bullosa and deafness #609057 in OMIM (no inheritance pattern given). 2 patients are described as having proteinuria in the nephrotic range among other features.

3 cases plus mouse model that replicates the kidney phenotype:

PMID: 15265795 - Karamatic Crew et al 2004 - report two sibs and a third unrelated patient, all of Indian Jewish origin who lack the MER2 antigen and have made anti-MER2. All had end-stage kidney disease. The two sibs had other phenotypic features such as pretibial bullous skin lesions, neurosensory deafness, bilateral lacrimal duct stenosis, nail dystrophy, and β-thalassemia minor. Less information available about the 3rd patient. Direct sequencing of all CD151 exons revealed a homozygous single nucleotide insertion G383 which causes a frameshift after Lys127, introducing a premature stop signal at codon 140. Ages of patients are not given.

PMID: 29138120 - Vahidnezhad et al 2018 - report 1 consangineous family with Epidermolysis bullosa which was screened using a gene panel and NGS. A homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) was found. In this family the 33-year old proband, initially diagnosed as Kindler syndrome, had widespread blistering, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. (Abstract only accessed).

PMID: 17015618 - Sachs et al 2006 - report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. The skin and hearing phenotypes were not observed.; to: Associated with Nephropathy with pretibial epidermolysis bullosa and deafness #609057 in OMIM (no inheritance pattern given). 2 patients are described as having proteinuria in the nephrotic range among other features.

3 cases (but 2 have the same variant - founder effect?) plus mouse model that replicates the kidney phenotype:

PMID: 15265795 - Karamatic Crew et al 2004 - report two sibs and a third unrelated patient, all of Indian Jewish origin who lack the MER2 antigen and have made anti-MER2. All had end-stage kidney disease. The two sibs had other phenotypic features such as pretibial bullous skin lesions, neurosensory deafness, bilateral lacrimal duct stenosis, nail dystrophy, and β-thalassemia minor. Less information available about the 3rd patient. Direct sequencing of all CD151 exons revealed a homozygous single nucleotide insertion G383 which causes a frameshift after Lys127, introducing a premature stop signal at codon 140. Ages of patients are not given.

PMID: 29138120 - Vahidnezhad et al 2018 - report 1 consangineous family with Epidermolysis bullosa which was screened using a gene panel and NGS. A homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) was found. In this family the 33-year old proband, initially diagnosed as Kindler syndrome, had widespread blistering, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. (Abstract only accessed).

PMID: 17015618 - Sachs et al 2006 - report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. The skin and hearing phenotypes were not observed.
Proteinuric renal disease v2.23 CD151 Eleanor Williams Publications for gene: CD151 were set to 15265795; 17015618; 29138120
Proteinuric renal disease v2.22 CD151 Eleanor Williams Publications for gene: CD151 were set to 15265795
Proteinuric renal disease v2.21 CD151 Eleanor Williams Mode of inheritance for gene: CD151 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.20 CD151 Eleanor Williams Classified gene: CD151 as Green List (high evidence)
Proteinuric renal disease v2.20 CD151 Eleanor Williams Added comment: Comment on list classification: 3 cases reported plus mouse model
Proteinuric renal disease v2.20 CD151 Eleanor Williams Gene: cd151 has been classified as Green List (High Evidence).
Proteinuric renal disease v2.19 CD151 Eleanor Williams commented on gene: CD151: Associated with Nephropathy with pretibial epidermolysis bullosa and deafness #609057 in OMIM (no inheritance pattern given). 2 patients are described as having proteinuria in the nephrotic range among other features.

3 cases plus mouse model that replicates the kidney phenotype:

PMID: 15265795 - Karamatic Crew et al 2004 - report two sibs and a third unrelated patient, all of Indian Jewish origin who lack the MER2 antigen and have made anti-MER2. All had end-stage kidney disease. The two sibs had other phenotypic features such as pretibial bullous skin lesions, neurosensory deafness, bilateral lacrimal duct stenosis, nail dystrophy, and β-thalassemia minor. Less information available about the 3rd patient. Direct sequencing of all CD151 exons revealed a homozygous single nucleotide insertion G383 which causes a frameshift after Lys127, introducing a premature stop signal at codon 140. Ages of patients are not given.

PMID: 29138120 - Vahidnezhad et al 2018 - report 1 consangineous family with Epidermolysis bullosa which was screened using a gene panel and NGS. A homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) was found. In this family the 33-year old proband, initially diagnosed as Kindler syndrome, had widespread blistering, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. (Abstract only accessed).

PMID: 17015618 - Sachs et al 2006 - report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria caused by focal glomerulosclerosis, disorganization of the glomerular basement membrane, and tubular cystic dilation. The skin and hearing phenotypes were not observed.
Proteinuric renal disease v2.19 APOE Eleanor Williams commented on gene: APOE: Set Penetrance to incomplete as several reports of unaffected individuals who carry the same variants as affected individuals.
Proteinuric renal disease v2.19 APOE Eleanor Williams Source Expert list was removed from APOE.
Source Literature was added to APOE.
Penetrance for gene APOE was set from to None
Proteinuric renal disease v2.18 APOE Eleanor Williams Publications for gene: APOE were set to 10432380; 9176854; 18077821
Proteinuric renal disease v2.17 APOE Eleanor Williams Classified gene: APOE as Green List (high evidence)
Proteinuric renal disease v2.17 APOE Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to green as many published cases of variants in APOE in patients with Lipoprotein glomerulopathy
Proteinuric renal disease v2.17 APOE Eleanor Williams Gene: apoe has been classified as Green List (High Evidence).
Proteinuric renal disease v2.16 APOE Eleanor Williams changed review comment from: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry for example (PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019




; to: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry (for example PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019
Proteinuric renal disease v2.16 APOE Eleanor Williams changed review comment from: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

PMID: 10432380 - Matsunaga et al 1999 - 32-year-old Japanese male patient with Lipoprotein glomerulopathy, whose history included proteinuria. A heterogyzous missense variant was identified termed apo E2 (Arg25Cys) Kyoto. His asymptomatic mother was also heterogyzous for this same variant.

PMID: 9176854 - Oikawa et al 1997 - report 3 patients with LPG from two families all with the same variant apo E Arg145Pro named APOE Sendai. Only the APOE gene was looked at.

PMID: 18077821 - Rovin et al 2007 - report two unrelated American men of European ancestry who presented with edema and proteinuria in the nephrotic range. Both patients had a heterozygous C→T transition resulting in an amino acid change Arg25Cys. Several female family members were heterozygous carriers of Arg25Cys, none had clinical evidence of lipoprotein glomerulopathy.

Review to be continued; to: Associated with Lipoprotein glomerulopathy #611771 in OMIM. No inheritance pattern listed.

Several publications report variants in the APOE gene in association with Lipoprotein glomerulopathy, mostly in individuals of Asian ethnicity but also in those with European ancestry for example (PMID: 18077821 - Rovin et al 2007). PMID: 31092271 - Xie et al 2019 lists many of the published variants (~12 to date, mostly point mutations, but also some deletions)

In several cases clinical asymptomatic carriers (all female?) also carry the same variants as probands e.g.
PMID: 18077821 - Rovin et al 2007
PMID: 10432380 - Matsunaga et al 1999
PMID: 31092271 - Xie et al 2019
Proteinuric renal disease v2.16 APOE Eleanor Williams commented on gene: APOE
Proteinuric renal disease v2.16 AMN Eleanor Williams Classified gene: AMN as Green List (high evidence)
Proteinuric renal disease v2.16 AMN Eleanor Williams Added comment: Comment on list classification: Changing rating from amber to green following expert review stating that proteinuria is a well known presenting feature of IMERSLUND-GRASBECK SYNDROME. At least 3 cases with variants in AMN and proteinuria are reported in the literature.
Proteinuric renal disease v2.16 AMN Eleanor Williams Gene: amn has been classified as Green List (High Evidence).
Proteinuric renal disease v2.15 AMN Eleanor Williams commented on gene: AMN: Associated with Megaloblastic anemia-1, Norwegian type #261100 (AR) in OMIM which is also known as IMERSLUND-GRASBECK SYNDROME (IGS).

PMID: 30691194 - Pacitto et al 2019 - describe a case of IGS with urinary tract infection and mild but persistent proteinuria at onset in an 11-month-old female child. The patient was found to be compound heterzygous for a novel intronic variant c.513+5G>A thought to affect a donor splice site, and the known pathogenetic variant c.1006+34_1007-31del. Parents each had one of the variants.

PMID: 26040326 - Montgomery et al 2015 - 2 half sisters with IGS and compound heterzygous variants in AMN are reported (c.35delA, p.Gln12Argfs*5) and (c.206 T > A, p.Met69Lys). Both presented with sub-nephrotic range proteinuria.

PMID: 22631584 - Densupsoontorn et al 2012 - report a Thai boy with IGS in whom a deleterious mutation in AMN was confirmed (homozygous c.663G>A; W221X). Persistent proteinuria was reported.

Note - not all patients are described as presenting with proteinuria e.g. PMID: 14593474 (Molecular cause of IGS unknown in this case).
Proteinuric renal disease v2.15 DGKE Eleanor Williams Classified gene: DGKE as Green List (high evidence)
Proteinuric renal disease v2.15 DGKE Eleanor Williams Added comment: Comment on list classification: Changing rating to green as multiple cases reported and expert review says proteinuria is a prominent feature
Proteinuric renal disease v2.15 DGKE Eleanor Williams Gene: dgke has been classified as Green List (High Evidence).
Proteinuric renal disease v2.14 DGKE Eleanor Williams Mode of inheritance for gene: DGKE was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.13 TPRKB Eleanor Williams Classified gene: TPRKB as Green List (high evidence)
Proteinuric renal disease v2.13 TPRKB Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green, as there are 3 reported cases.
Proteinuric renal disease v2.13 TPRKB Eleanor Williams Gene: tprkb has been classified as Green List (High Evidence).
Proteinuric renal disease v2.12 TPRKB Eleanor Williams Mode of inheritance for gene: TPRKB was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.11 TPRKB Eleanor Williams Publications for gene: TPRKB were set to 28805828
Proteinuric renal disease v2.10 PTPRO Eleanor Williams Classified gene: PTPRO as Amber List (moderate evidence)
Proteinuric renal disease v2.10 PTPRO Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber. 2 families reported.
Proteinuric renal disease v2.10 PTPRO Eleanor Williams Gene: ptpro has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.9 KANK2 Eleanor Williams Classified gene: KANK2 as Amber List (moderate evidence)
Proteinuric renal disease v2.9 KANK2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber - 2 reported cases.
Proteinuric renal disease v2.9 KANK2 Eleanor Williams Gene: kank2 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.8 CD2AP Catherine Snow Mode of inheritance for gene: CD2AP was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.7 CD2AP Catherine Snow Classified gene: CD2AP as Amber List (moderate evidence)
Proteinuric renal disease v2.7 CD2AP Catherine Snow Gene: cd2ap has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.6 DGKE Catherine Snow Classified gene: DGKE as Amber List (moderate evidence)
Proteinuric renal disease v2.6 DGKE Catherine Snow Gene: dgke has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v2.5 Eleanor Williams Panel version has been signed off
Proteinuric renal disease v2.3 Eleanor Williams Panel version has been signed off
Proteinuric renal disease v2.0 DGKE Eleanor Williams edited their review of gene: DGKE: Added comment: Associated with Nephrotic syndrome, type 7 #615008 (AR) in OMIM.

PMID: 23542698 - Lemaire et al 2013 - 9 families identified with homozgyous or compound heterozygous variants in DGKE. All were cases of pediatric-onset aHUS. One variant was found in on both alleles in 3 families (p.Trp322*) and heterozygously in 2 others and the families are thought to have a remote shared ancestry. Three patients from different families developed nephrotic syndrome 3-5 years after disease onset.

PMID: 23274426 - Ozaltin et al 2013 - 3 consanguineous families - 3 different homozygous variants in 9 individuals. Table 1 gives proteinuria levels at onset.; Changed publications: PMID: 23274426, PMID: 23542698
Proteinuric renal disease v2.0 KANK2 Eleanor Williams commented on gene: KANK2: Associated with Nephrotic syndrome, type 16 #617783 (AR) in OMIM.

PMID: 25961457 - Gee et al 2015 - performed homozygosity mapping and whole-exome sequencing in individuals with NS identified recessive mutations in KANK2 in two families with NS. In family A982 of Arab origin, 2 siblings had early-onset SSNS and were found to have a homozygous missense mutation c.541A>G;p.S181G in KANK2. It segregated with the disorder in the family. In an unrelated individual with SSNS (A1751-21), they found a homozygous missense mutation (c.2051C>T;p.S684F) in KANK2. 27 known genes previously linked to SRNS were screened in this individual, but no explanatory mutations were detected. Knockdown of kank2 in zebrafish results in proteinuria which could be partially rescued by wild type human KANK2 mRNA but not either of the mutant mRNAs.

My reading of Table 1 is that there were two cases - one family with two siblings (individuals A982-21 and A982-22) with the same variant, and a second unrelated individual (A1751-21) with a different missense variant.
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 PTPRO Eleanor Williams edited their review of gene: PTPRO: Added comment: Associated with Nephrotic syndrome, type 6 #614196 (AR) in OMIM.

2 families:

PMID: 21722858 - Ozaltin et al 2011 - 2 Turkish families reported, total of 5 individuals. A region of homozygosity was identified in a consangiuneous family with Idiopathic nephrotic syndrome. By direct sequencing of PTPRO a homozygous c.2627+1G>T donor splice-site mutation was identified. In a second family, a c.2745+1G>A donor splice-site mutation in PTPRO was identified. Electron microscopy identified ultrastructural alterations in podocytes in both families.

PMID: 30065916 - Trautmann et al 2018 - PodoNet Registry paper - describes the same families as Ozaltin et al.; Changed publications: PMID: 21722858, PMID: 30065916
Proteinuric renal disease v2.0 CD2AP Eleanor Williams edited their review of gene: CD2AP: Changed publications: 30612599, 17713465, 10514378, 12764198
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: 12764198 - Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 CD2AP Eleanor Williams changed review comment from: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal effect. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIVE-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; to: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal involvement. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIV-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).
Proteinuric renal disease v2.0 CD2AP Eleanor Williams edited their review of gene: CD2AP: Added comment: Associated with Glomerulosclerosis, focal segmental, 3 #607832 in OMIM (no inheritance given)

Mouse knockout model supports renal effect. 2 cases with heterozgous variants and FSGS but only CD2AP looked at. Two familial cases of homozygous variants (in one only CD2AP screened) and FSGS.

PMID: 10514378 - Shih et al 1999 - In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells.

PMID: Kim et al 2003 - CD2AP+/- showed glomerular abnormalities at 9 months of age but not proteinuria. Screened 30 African-Americans with idiopathic FSGS and 15 African-Americans with HIVE-associated FSGS for changes in CD2AP. One variant, predicted to affect the splice acceptor of exon 7 in one allele, was found in 2 patients with primary FSGS and expression of the protein was lower in these patients.

PMID:17713465 - Löwik et al 2007 - report a homozygous variant in a proband with primary Focal segmental glomerulosclerosis, from a consanguineous family of Mediterranean ancestry. A homozygous c1834 C>T (R612Stop) variant was found. Both parents were proven to be heterozygous for this mutation. An immunoblot shows no CD2AP expression in the patient carrying the R612Stop mutation homozygously

PMID: 30612599 - Takano et al 2019 - Using WES, they identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. (Abstract only accessed).; Changed publications: PMID: 30612599, PMID: 17713465
Proteinuric renal disease v2.0 TPRKB Eleanor Williams commented on gene: TPRKB: TPRKB is associated with Galloway-Mowat syndrome 5 #617731 (AR) in OMIM.

PMID: 28805828 - Braun et al 2017 - screened the coding regions of OSGEP, TP53RK, TPRKB and LAGE3 in 907 individuals with early-onset nephrotic syndrome including 91 individuals with GAMOS. Identified 2 biallelic missense variants in TPRKB in 2 families with GAMOS (c.407T>C, p.Leu136Pro and c.446A>6, p.Tyr149Cys). Both sets of parents were heterozgous for the variant. Mouse embryos with knockout of Lage3, Osgep, or Tprkb reproduced the human microcephaly phenotype. No renal phenotype was observed in knockout mice or fish but they hypothesize that this is due to early lethality masking renal involvement that might occur in older animals. Functional studies also showed that knockout of these genes affect cell proliferation.

PMID: 30053862 - Hyun et al 2018 - WES on a family with three GAMOS affected siblings found a homozygous missense mutation (NM_033550, c.194A > T, p.Lys65Met) in 2 siblings (3rd not tested). Parents and an unaffected sibling were heterzygous for the variant. All three patients manifested similar phenotypes, including very early-onset nephrotic syndrome, microcephaly, dysmorphic faces, and early fatality. Renal biopsy performed on one patient revealed focal segmental glomerulosclerosis with severe tubulo-interstitial changes.

Summary: 3 familial cases. Some functional data.
Proteinuric renal disease v2.0 FN1 Zornitza Stark gene: FN1 was added
gene: FN1 was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: FN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FN1 were set to 18268355
Phenotypes for gene: FN1 were set to Glomerulopathy with fibronectin deposits 2, MIM# 601894
Review for gene: FN1 was set to GREEN
gene: FN1 was marked as current diagnostic
Added comment: Six unrelated families reported; mostly a nephrotic picture with some haematuria.
Sources: Expert list
Proteinuric renal disease v2.0 CD151 Zornitza Stark reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.0 TPRKB chirag patel reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, OMIM #617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 PTPRO Zornitza Stark reviewed gene: PTPRO: Rating: AMBER; Mode of pathogenicity: None; Publications: 21722858, 30065916; Phenotypes: Nephrotic syndrome, type 6 #614196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 KANK2 Zornitza Stark reviewed gene: KANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25961457; Phenotypes: Nephrotic syndrome, type 16, MIM#617783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 DGKE Zornitza Stark reviewed gene: DGKE: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542698, 23274426; Phenotypes: Nephrotic syndrome, type 7, MIM# 615008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.0 CD2AP chirag patel Deleted their review
Proteinuric renal disease v2.0 CD2AP chirag patel reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30612599, 17713465; Phenotypes: Glomerulosclerosis, focal segmental, 3, OMIM #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 CD2AP Zornitza Stark reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: 17713465, 30612599; Phenotypes: Glomerulosclerosis, focal segmental, 3 #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v2.0 APOE Zornitza Stark gene: APOE was added
gene: APOE was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: APOE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APOE were set to 10432380; 9176854; 18077821
Phenotypes for gene: APOE were set to Lipoprotein glomerulopathy, MIM# 611771
Review for gene: APOE was set to GREEN
Added comment: Specific variants in Japanese/Chinese linked to the development of a glomerulopathy, characterised by proteinuria, renal failure and deposition of lipoprotein thrombi.
Sources: Expert list
Proteinuric renal disease v2.0 AMN Zornitza Stark reviewed gene: AMN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30691194, 26040326; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v2.0 Eleanor Williams promoted panel to version 2.0
Proteinuric renal disease v1.227 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Proteinuric renal disease v1.226 FAT1 Eleanor Williams changed review comment from: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there is sufficient pedigrees and strong enough functional data to rate this gene green.; to: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there are sufficient pedigrees and strong enough functional data to rate this gene green.
Proteinuric renal disease v1.226 CLCN5 Eleanor Williams commented on gene: CLCN5: Changed Mode of inheritance to X linked: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) because PMID: 25907713 reports that female carriers can have mild symptoms of Dent disease
Proteinuric renal disease v1.226 CLCN5 Eleanor Williams Mode of inheritance for gene: CLCN5 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.225 CLCN5 Eleanor Williams changed review comment from: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females. However, PMID: 25907713 reports that female carriers can have mild symptoms of Dents disease so Xlinked (monoalllelic in females) may be more appropriate.; to: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females. However, PMID: 25907713 reports that female carriers can have mild symptoms of Dent disease so Xlinked (monoalllelic in females) may be more appropriate.
Proteinuric renal disease v1.225 CLCN5 Eleanor Williams changed review comment from: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females. However, PMID: 25907713 reports that female carriers can have mild symptoms so Xlinked (monoalllelic in females) may be more appropriate.; to: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females. However, PMID: 25907713 reports that female carriers can have mild symptoms of Dents disease so Xlinked (monoalllelic in females) may be more appropriate.
Proteinuric renal disease v1.225 CLCN5 Eleanor Williams changed review comment from: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females; to: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females. However, PMID: 25907713 reports that female carriers can have mild symptoms so Xlinked (monoalllelic in females) may be more appropriate.
Proteinuric renal disease v1.225 OCRL Eleanor Williams changed review comment from: Associated with Dent disease 2 (300555) and Lowe syndrome (309000) in OMIM.

PMID: 21249396 - Tasic et al 2011 - 5 unrelated Macedonian patients with 4 different variants in OCRL. 2 diagnosed with Lowe Syndrome (both with LMWP and hypercalciuria) and 3 with Dent disease 2 (all with asymptomatic proteinuria). All five patients had LMWP and hypercalciuria/


PMID: 17384968 - Sekine et al 2007 - 3 distinct OCRL1 mutations in 3 patients with the Dent disease phenotype are described. All the patients manifested an extremely high degree of low-molecular-weight proteinuria and showed no ocular abnormalities or apparent mental retardation. Urinalysis and blood chemistry showed no findings suggestive of Fanconi syndrome with renal tubular acidosis. Mutations in CLCN5 were ruled out. The mutations identified in OCRL1 are one frame-shift mutation (I127stop) and two missense mutations (R301C and R476W).

PMID: 27625797 - Böckenhauer et al 2012 - 14 CLCN5-negative patients from 12 families with a phenotype resembling Dent disease were assessed for defects in OCRL. In six of these kindreds three novel (c.149+1G>A, c.1126A>T, c.1547T>C) and three repeatedly observed mutations (c.166_167delTT, c.901C>T, c.1426C>T) were discovered. All showed low molecular weight proteinuria.; to: Associated with Dent disease 2 (300555) and Lowe syndrome (309000) in OMIM.

PMID: 21249396 - Tasic et al 2011 - 5 unrelated Macedonian patients with 4 different variants in OCRL. 2 diagnosed with Lowe Syndrome (both with LMWP and hypercalciuria) and 3 with Dent disease 2 (all with asymptomatic proteinuria). All five patients had LMWP and hypercalciuria. Sex of patients not stated.


PMID: 17384968 - Sekine et al 2007 - 3 distinct OCRL1 mutations in 3 male patients with the Dent disease phenotype are described. All the patients manifested an extremely high degree of low-molecular-weight proteinuria and showed no ocular abnormalities or apparent mental retardation. Urinalysis and blood chemistry showed no findings suggestive of Fanconi syndrome with renal tubular acidosis. Mutations in CLCN5 were ruled out. The mutations identified in OCRL1 are one frame-shift mutation (I127stop) and two missense mutations (R301C and R476W).

PMID: 27625797 - Böckenhauer et al 2012 - 14 CLCN5-negative patients from 12 families with a phenotype resembling Dent disease were assessed for defects in OCRL. In six of these kindreds three novel (c.149+1G>A, c.1126A>T, c.1547T>C) and three repeatedly observed mutations (c.166_167delTT, c.901C>T, c.1426C>T) were discovered. All showed low molecular weight proteinuria. Sex of patients not explicitly stated but each had mothers who were 'carriers'.
Proteinuric renal disease v1.225 CLCN5 Eleanor Williams edited their review of gene: CLCN5: Added comment: Note on Mode of inheritance - OMIM list the mode of inheritance for both Dent disease #300009; Proteinuria low molecular weight #308990 as XLR so have left mode of inheritance as X-LINKED: hemizygous mutation in males, biallelic mutations in females; Changed publications: PMID27757584, PMID: 25907713; Changed phenotypes: Dent disease #300009, Proteinuria low molecular weight #308990
Proteinuric renal disease v1.225 LAMA5 Eleanor Williams Phenotypes for gene: LAMA5 were changed from to Nephrotic syndrome
Proteinuric renal disease v1.224 LAMA5 Eleanor Williams Mode of inheritance for gene: LAMA5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.223 LAMA5 Eleanor Williams Classified gene: LAMA5 as Amber List (moderate evidence)
Proteinuric renal disease v1.223 LAMA5 Eleanor Williams Added comment: Comment on list classification: Changing the rating of this gene to Amber. 3 cases with homozygous missense variants reported but authors classify as VUS as there is no experimental evidence to link the impact of these genetic variants on protein function to disease pathogenesis.
Proteinuric renal disease v1.223 LAMA5 Eleanor Williams Gene: lama5 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.222 Eleanor Williams List of related panels changed from to R195
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. There is evolutionary conservation at these sites. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Proteinuric renal disease v1.221 LAMA5 Eleanor Williams commented on gene: LAMA5: Not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 29534211 - Braun et al 2019 - performed WES in 335 individuals of 300 families with Nephrotic syndrome and identified recessive mutations in the gene LAMA5 in three unrelated consanguineous families with childhood-onset NS that responded to immunosuppressive therapy. The 3 families were from Turkey, Egypt and Saudia Arabia and the following 3 missense variants were found - family A4389: c.2239 C >T, p.Arg747Trp, family B150: c.3002 A>G, p.Glu1001Gly, family B1284: c.8842 G>A, p.Gly2948Ser. In two families, the parents were shown to be heterozygous for the variants. None of the three variants has been reported in the homozygous state in databases of healthy control populations (EVS and gnomAD) although individuals of Middle Eastern descent are poorly represented in these databases. The authors state that because experimental evidence is lacking, the impact of these genetic variants on protein function and disease pathogenesis cannot be judged with certainty.
Proteinuric renal disease v1.221 LAMA5 Zornitza Stark reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 29534211; Phenotypes: Nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.221 PDSS2 Eleanor Williams changed review comment from: Comment on list classification: 4 cases plus a mouse knock out model.; to: Comment on list classification: Upgraded from red to green. 4 cases plus a mouse knock out model.
Proteinuric renal disease v1.221 PDSS2 Eleanor Williams Publications for gene: PDSS2 were set to 23926186
Proteinuric renal disease v1.220 PDSS2 Eleanor Williams Mode of inheritance for gene: PDSS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Classified gene: PDSS2 as Green List (high evidence)
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Added comment: Comment on list classification: 4 cases plus a mouse knock out model.
Proteinuric renal disease v1.219 PDSS2 Eleanor Williams Gene: pdss2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.218 PDSS2 Eleanor Williams edited their review of gene: PDSS2: Added comment: The gene is associated with Coenzyme Q10 deficiency, primary, 3 (#614652) in OMIM and COENZYME Q10 DEFICIENCY, PRIMARY, 3 (confirmed) in Gene2Phenotype.

PMID: 29032433 - Iványi et al 2018 - 1 case - male child of healthy, nonconsanguineous Caucasian parents. At 7 months of age he had general edema, muscle hypotonia, mild inspiratory stridor, and global developmental delay. He did not react to auditory stimuli, and they detected no tracking and focusing eye movements. Urinalysis revealed proteinuria. A heterozygous missense mutation in the PDSS2 gene in exon 3 was found (c.485A > G, p.His162Arg) (maternally inherited) along with a heterozygous 2923-bp deletion that affected a part of exon 8 in the PDSS2 gene. The paternal allele is the NM_020381.3:c.1042_1148-2816del, which causes a 107-base long deletion of exon 8. Despite high-dose CoQ10 treatment he died at 8 months of age.

PMID: 25349199 - Sadowski et al 2015 - 2 cases with homozygous missense changes in PDSS2 in patients with Steroid-resistant nephrotic syndrome. They performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with Steroid-resistant nephrotic syndrome (SRNS) and then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. 2 families were molecularly diagnosed with a causative variant in PDSS2 by multiplex PCR (c.1145C>T,p.Ser382Leu and c.1151C>A, p.Ala384Asp).

PMID: 23926186 - Gasser et al 2013 - genotyped 377 patients with primary Focal segmental glomerulosclerosis (FSGS) or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. The nine selected SNPs were distributed at approximately equal distances across the PDSS2 gene. All the SNPs that were genotyped occurred within noncoding regions of the gene. They demonstrated that homozygous genotypes for variant alleles for the PDSS2 gene were more common in FSGS patients than controls and that a single haplotype containing three of these SNPs was more common in European American, but not African American, FSGS patients, suggesting that PDSS2 may be an FSGS susceptibility gene.

PMID:17186472 - Lopez et al 2006 - 1 family with child who presented with neonatal pneumonia and hypotonia, developed refractory left-sided seizures with secondary generalization, and became progressively floppy. At age 7 mo, severe episodic vomiting prompted duodenal tube feeding, and was diagnosed with nephrotic syndrome due to low serum albumin and massive proteinuria. They found two nonsynonymous nucleotide changes in PDSS2, each inherited from one parent. Functional tests on cultured patient fibroblast indicate that endogenous levels of decaprenyl diphosphate are reduced.

Mouse model:
PMID: 18437205 - Peng et al 2008 - Kidney disease in mice with missense Pdss2(kd/kd) genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd) mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP) knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes.

Summary:
4 cases of children with nephrotic syndrome and homozygous or compound heterozygous variants in PDSS2. In two cases the variants are reported to segregate with the disease in the family. Additional evidence from a case control study that PDSS2 is a FSGS susceptibility gene and from a mouse Pdss2 knockout model.; Changed publications: PMID: 23926186
Proteinuric renal disease v1.218 LCAT Eleanor Williams Classified gene: LCAT as Amber List (moderate evidence)
Proteinuric renal disease v1.218 LCAT Eleanor Williams Added comment: Comment on list classification: Changing the rating from green to amber until a review of the degree of proteinuria in patients with Norum disease has been carried out.
Proteinuric renal disease v1.218 LCAT Eleanor Williams Gene: lcat has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.217 AMN Eleanor Williams Classified gene: AMN as Amber List (moderate evidence)
Proteinuric renal disease v1.217 AMN Eleanor Williams Added comment: Comment on list classification: Changing rating from green to amber until a review of the degree of proteinuria in patients with Imerslund-Grasbeck syndrome has been done.
Proteinuric renal disease v1.217 AMN Eleanor Williams Gene: amn has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Classified gene: DLC1 as Green List (high evidence)
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Added comment: Comment on list classification: Plausible disease causing variants found in more than 3 cases.
Proteinuric renal disease v1.216 DLC1 Eleanor Williams Gene: dlc1 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Classified gene: NUP133 as Green List (high evidence)
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Added comment: Comment on list classification: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of Galloway-Mowat syndrome. Sufficient cases to rate green.
Proteinuric renal disease v1.215 NUP133 Eleanor Williams Gene: nup133 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.214 WDR73 Eleanor Williams Mode of inheritance for gene: WDR73 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Classified gene: WDR73 as Green List (high evidence)
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Added comment: Comment on list classification: Sufficient cases and GMS renal specialist test group decided Galloway-Mowat syndrome is appropriate for this panel
Proteinuric renal disease v1.213 WDR73 Eleanor Williams Gene: wdr73 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.212 XPO5 Eleanor Williams Phenotypes for gene: XPO5 were changed from to Nephrotic syndrome
Proteinuric renal disease v1.211 XPO5 Eleanor Williams Publications for gene: XPO5 were set to
Proteinuric renal disease v1.210 SLC19A3 Eleanor Williams Phenotypes for gene: SLC19A3 were changed from Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive; (originally on the Imerslund-Grasbeck syndrome gene panel) to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) #607483; (originally on the Imerslund-Grasbeck syndrome gene panel)
Proteinuric renal disease v1.209 NXF5 Eleanor Williams Phenotypes for gene: NXF5 were changed from to FSGS; heart-block disorder
Proteinuric renal disease v1.208 NXF5 Eleanor Williams Publications for gene: NXF5 were set to
Proteinuric renal disease v1.207 NLRP3 Eleanor Williams Phenotypes for gene: NLRP3 were changed from to SRNS
Proteinuric renal disease v1.206 NLRP3 Eleanor Williams Publications for gene: NLRP3 were set to
Proteinuric renal disease v1.205 NEU1 Eleanor Williams Phenotypes for gene: NEU1 were changed from to SRNS
Proteinuric renal disease v1.204 NEU1 Eleanor Williams Publications for gene: NEU1 were set to
Proteinuric renal disease v1.203 NEIL1 Eleanor Williams Phenotypes for gene: NEIL1 were changed from to SRNS
Proteinuric renal disease v1.202 NEIL1 Eleanor Williams Publications for gene: NEIL1 were set to
Proteinuric renal disease v1.201 LAMA5 Eleanor Williams Publications for gene: LAMA5 were set to
Proteinuric renal disease v1.200 KANK4 Eleanor Williams Publications for gene: KANK4 were set to
Proteinuric renal disease v1.199 KANK1 Eleanor Williams Phenotypes for gene: KANK1 were changed from to Steroid sensitive resistant nephrotic syndrome
Proteinuric renal disease v1.198 KANK1 Eleanor Williams Publications for gene: KANK1 were set to
Proteinuric renal disease v1.197 E2F3 Eleanor Williams Phenotypes for gene: E2F3 were changed from to FSGS; mental retardation
Proteinuric renal disease v1.196 E2F3 Eleanor Williams Publications for gene: E2F3 were set to
Proteinuric renal disease v1.195 CYP11B2 Eleanor Williams Phenotypes for gene: CYP11B2 were changed from to Hypoaldosteronism, congenital, due to CMO I deficiency #203400; Hypoaldosteronism, congenital, due to CMO II deficiency #610600
Proteinuric renal disease v1.194 CYP11B2 Eleanor Williams Publications for gene: CYP11B2 were set to
Proteinuric renal disease v1.193 COQ9 Eleanor Williams Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5 #614654
Proteinuric renal disease v1.192 COQ9 Eleanor Williams Publications for gene: COQ9 were set to
Proteinuric renal disease v1.191 COQ7 Eleanor Williams Phenotypes for gene: COQ7 were changed from to ?Coenzyme Q10 deficiency, primary, 8 #616733
Proteinuric renal disease v1.190 COQ7 Eleanor Williams Publications for gene: COQ7 were set to
Proteinuric renal disease v1.189 COL4A1 Eleanor Williams Phenotypes for gene: COL4A1 were changed from to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps #611773
Proteinuric renal disease v1.188 COL4A1 Eleanor Williams Publications for gene: COL4A1 were set to
Proteinuric renal disease v1.187 CDK20 Eleanor Williams Phenotypes for gene: CDK20 were changed from to Chronic kidney disease
Proteinuric renal disease v1.186 CDK20 Eleanor Williams Publications for gene: CDK20 were set to
Proteinuric renal disease v1.185 CD151 Eleanor Williams Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness #609057
Proteinuric renal disease v1.184 CD151 Eleanor Williams Publications for gene: CD151 were set to
Proteinuric renal disease v1.183 ARHGAP24 Eleanor Williams Phenotypes for gene: ARHGAP24 were changed from to Focal segmental glomerulosclerosis
Proteinuric renal disease v1.182 ARHGAP24 Eleanor Williams Publications for gene: ARHGAP24 were set to
Proteinuric renal disease v1.181 ANKFY1 Eleanor Williams Publications for gene: ANKFY1 were set to
Proteinuric renal disease v1.180 ZMPSTE24 Eleanor Williams Phenotypes for gene: ZMPSTE24 were changed from to Mandibuloacral dysplasia with type B lipodystrophy #608612
Proteinuric renal disease v1.179 ZMPSTE24 Eleanor Williams Publications for gene: ZMPSTE24 were set to
Proteinuric renal disease v1.178 VPS33B Eleanor Williams Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 #208085
Proteinuric renal disease v1.177 VPS33B Eleanor Williams Publications for gene: VPS33B were set to
Proteinuric renal disease v1.176 VIPAS39 Eleanor Williams Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2 # 613404
Proteinuric renal disease v1.175 VIPAS39 Eleanor Williams Publications for gene: VIPAS39 were set to
Proteinuric renal disease v1.174 TTC21B Eleanor Williams Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12 # 613820
Proteinuric renal disease v1.173 TTC21B Eleanor Williams Publications for gene: TTC21B were set to
Proteinuric renal disease v1.172 TPRKB Eleanor Williams Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5 #617731
Proteinuric renal disease v1.171 TPRKB Eleanor Williams Publications for gene: TPRKB were set to
Proteinuric renal disease v1.170 SYNPO Eleanor Williams Phenotypes for gene: SYNPO were changed from to Focal segmental glomerulosclerosis; FSGS
Proteinuric renal disease v1.169 SYNPO Eleanor Williams Publications for gene: SYNPO were set to
Proteinuric renal disease v1.168 PTPRO Eleanor Williams Phenotypes for gene: PTPRO were changed from to Nephrotic syndrome, type 6 #614196
Proteinuric renal disease v1.167 PTPRO Eleanor Williams Publications for gene: PTPRO were set to
Proteinuric renal disease v1.166 PMM2 Eleanor Williams Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia #212065
Proteinuric renal disease v1.165 PMM2 Eleanor Williams Publications for gene: PMM2 were set to
Proteinuric renal disease v1.164 NUP205 Eleanor Williams Phenotypes for gene: NUP205 were changed from to ?Nephrotic syndrome, type 13 #616893
Proteinuric renal disease v1.163 NUP205 Eleanor Williams Publications for gene: NUP205 were set to
Proteinuric renal disease v1.162 NUP160 Eleanor Williams Phenotypes for gene: NUP160 were changed from to ?Nephrotic syndrome, type 19 #618178
Proteinuric renal disease v1.161 NUP160 Eleanor Williams Publications for gene: NUP160 were set to
Proteinuric renal disease v1.160 NPHP4 Eleanor Williams Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4 #606966
Proteinuric renal disease v1.159 NPHP4 Eleanor Williams Publications for gene: NPHP4 were set to
Proteinuric renal disease v1.158 MEFV Eleanor Williams Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever, AR #249100
Proteinuric renal disease v1.157 MAFB Eleanor Williams Phenotypes for gene: MAFB were changed from to FSGS with Duane retraction syndrome
Proteinuric renal disease v1.156 MAFB Eleanor Williams Publications for gene: MAFB were set to
Proteinuric renal disease v1.155 LMNA Eleanor Williams Phenotypes for gene: LMNA were changed from to Partial lipodystrophy and FSGS
Proteinuric renal disease v1.154 LMNA Eleanor Williams Publications for gene: LMNA were set to
Proteinuric renal disease v1.153 LCAT Eleanor Williams Phenotypes for gene: LCAT were changed from to Norum disease #245900
Proteinuric renal disease v1.152 KANK2 Eleanor Williams Phenotypes for gene: KANK2 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome 16 #617783
Proteinuric renal disease v1.151 KANK2 Eleanor Williams Publications for gene: KANK2 were set to J Clin Invest. 2015; 125(6):2375–2384
Proteinuric renal disease v1.150 ITSN2 Eleanor Williams Phenotypes for gene: ITSN2 were changed from to Early childhood SSNS
Proteinuric renal disease v1.149 ITSN2 Eleanor Williams Publications for gene: ITSN2 were set to
Proteinuric renal disease v1.148 ITGB4 Eleanor Williams Phenotypes for gene: ITGB4 were changed from to Epidermolysis bullosa, junctional, with pyloric stenosis #226730
Proteinuric renal disease v1.147 ITGB4 Eleanor Williams Publications for gene: ITGB4 were set to
Proteinuric renal disease v1.146 ITGA3 Eleanor Williams Phenotypes for gene: ITGA3 were changed from to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital #614748
Proteinuric renal disease v1.145 GAPVD1 Eleanor Williams Publications for gene: GAPVD1 were set to
Proteinuric renal disease v1.144 DGKE Eleanor Williams Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7 #615008
Proteinuric renal disease v1.143 DGKE Eleanor Williams Publications for gene: DGKE were set to
Proteinuric renal disease v1.142 CD2AP Eleanor Williams Phenotypes for gene: CD2AP were changed from to Glomerulosclerosis, focal segmental, 3 #607832
Proteinuric renal disease v1.141 CD2AP Eleanor Williams Publications for gene: CD2AP were set to
Proteinuric renal disease v1.140 ARHGDIA Eleanor Williams Phenotypes for gene: ARHGDIA were changed from to Nephrotic syndrome, type 8 #615224
Proteinuric renal disease v1.139 ARHGDIA Eleanor Williams Publications for gene: ARHGDIA were set to
Proteinuric renal disease v1.137 APOL1 Eleanor Williams Phenotypes for gene: APOL1 were changed from to Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551
Proteinuric renal disease v1.136 APOL1 Eleanor Williams Publications for gene: APOL1 were set to
Proteinuric renal disease v1.135 ANLN Eleanor Williams Publications for gene: ANLN were set to 24676636
Proteinuric renal disease v1.134 AMN Eleanor Williams Publications for gene: AMN were set to 12590260
Proteinuric renal disease v1.133 ALMS1 Eleanor Williams Phenotypes for gene: ALMS1 were changed from to Alstrom Syndrome #203800
Proteinuric renal disease v1.132 ALMS1 Eleanor Williams Publications for gene: ALMS1 were set to
Proteinuric renal disease v1.131 ALG1 Eleanor Williams Phenotypes for gene: ALG1 were changed from to Congenital disorder of glycosylation, type Ik #608540
Proteinuric renal disease v1.130 ALG1 Eleanor Williams Publications for gene: ALG1 were set to
Proteinuric renal disease v1.129 WT1 Eleanor Williams Phenotypes for gene: WT1 were changed from to Denys-Drash syndrome #194080; Frasier syndrome #136680; Wilms tumor, type 1 #194070
Proteinuric renal disease v1.128 WT1 Eleanor Williams Publications for gene: WT1 were set to
Proteinuric renal disease v1.127 WDR73 Eleanor Williams Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 #251300
Proteinuric renal disease v1.126 WDR73 Eleanor Williams Publications for gene: WDR73 were set to
Proteinuric renal disease v1.125 TRPC6 Eleanor Williams Phenotypes for gene: TRPC6 were changed from to Glomerulosclerosis, focal segmental, 2 #603652; Proteinuria; FSGS; kidney failure; Familial and sporadic SRNS (adult)
Proteinuric renal disease v1.124 TRPC6 Eleanor Williams Publications for gene: TRPC6 were set to
Proteinuric renal disease v1.123 SMARCAL1 Eleanor Williams Phenotypes for gene: SMARCAL1 were changed from to Schimke immunoosseous dysplasia #242900
Proteinuric renal disease v1.122 SMARCAL1 Eleanor Williams Publications for gene: SMARCAL1 were set to
Proteinuric renal disease v1.121 SCARB2 Eleanor Williams Phenotypes for gene: SCARB2 were changed from to Action myoclonus renal failure syndrome; Epilepsy, progressive myoclonic 4, with or without renal failure #254900
Proteinuric renal disease v1.120 SCARB2 Eleanor Williams Publications for gene: SCARB2 were set to
Proteinuric renal disease v1.119 PLCE1 Eleanor Williams Phenotypes for gene: PLCE1 were changed from to Nephrotic syndrome, type 3 #610725; Congenital nephrotic syndrome/SRNS
Proteinuric renal disease v1.118 PLCE1 Eleanor Williams Publications for gene: PLCE1 were set to
Proteinuric renal disease v1.117 PDSS2 Eleanor Williams Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 #614652; Leigh syndrome
Proteinuric renal disease v1.116 PDSS2 Eleanor Williams Publications for gene: PDSS2 were set to
Proteinuric renal disease v1.115 NUP93 Eleanor Williams Phenotypes for gene: NUP93 were changed from Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome to Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome; Nephrotic syndrome, type 12 #616892
Proteinuric renal disease v1.114 NUP93 Eleanor Williams Publications for gene: NUP93 were set to Am J Hum Genet. 2015 Oct 1; 97(4):555-66
Proteinuric renal disease v1.113 NPHS2 Eleanor Williams Phenotypes for gene: NPHS2 were changed from to Nephrotic syndrome, type 2 #600995
Proteinuric renal disease v1.112 NPHS1 Eleanor Williams Phenotypes for gene: NPHS1 were changed from to Nephrotic syndrome, type 1 #602716
Proteinuric renal disease v1.111 MYO1E Eleanor Williams Phenotypes for gene: MYO1E were changed from to Glomerulosclerosis, focal segmental, 6 #614131
Proteinuric renal disease v1.110 MYO1E Eleanor Williams Publications for gene: MYO1E were set to PMID: 21697813
Proteinuric renal disease v1.109 MYH9 Eleanor Williams Phenotypes for gene: MYH9 were changed from to Epstein syndrome #153650; Fechtner syndrome #153640
Proteinuric renal disease v1.108 MYH9 Eleanor Williams Publications for gene: MYH9 were set to
Proteinuric renal disease v1.107 LMX1B Eleanor Williams Phenotypes for gene: LMX1B were changed from to Nail-patella syndrome #161200; FSGS; proteinuria; kidney failure; isolated glomerulopathy
Proteinuric renal disease v1.106 LMX1B Eleanor Williams Publications for gene: LMX1B were set to
Proteinuric renal disease v1.105 LAMB2 Eleanor Williams Publications for gene: LAMB2 were set to
Proteinuric renal disease v1.104 LAMB2 Eleanor Williams Phenotypes for gene: LAMB2 were changed from to Nephrotic syndrome, type 5, with or without ocular abnormalities #614199; Pierson syndrome #609049
Proteinuric renal disease v1.103 INF2 Eleanor Williams Publications for gene: INF2 were set to
Proteinuric renal disease v1.102 INF2 Eleanor Williams Phenotypes for gene: INF2 were changed from to Glomerulosclerosis, focal segmental, 5 #613237; Adult onset nephrotic syndrome (+CMT); FSGS; proteinuria; renal failure
Proteinuric renal disease v1.101 CUBN Eleanor Williams Publications for gene: CUBN were set to 21903995
Proteinuric renal disease v1.100 COQ6 Eleanor Williams Phenotypes for gene: COQ6 were changed from to Coenzyme Q10 deficiency, primary, 6 #614650
Proteinuric renal disease v1.99 COQ6 Eleanor Williams Publications for gene: COQ6 were set to
Proteinuric renal disease v1.98 COQ2 Eleanor Williams Publications for gene: COQ2 were set to 17855635; 29637272; 30180404
Proteinuric renal disease v1.98 COQ2 Eleanor Williams Phenotypes for gene: COQ2 were changed from Coenzyme Q10 deficiency, primary, 1 #607426 to Coenzyme Q10 deficiency, primary, 1 #607426
Proteinuric renal disease v1.97 COQ2 Eleanor Williams Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1 #607426
Proteinuric renal disease v1.96 COQ2 Eleanor Williams Publications for gene: COQ2 were set to PubMed: 17855635
Proteinuric renal disease v1.95 COL4A5 Eleanor Williams Phenotypes for gene: COL4A5 were changed from to Alports; Familial benign haematuria; Alport syndrome; proteinuria; haematuria; FSGS
Proteinuric renal disease v1.94 COL4A5 Eleanor Williams Publications for gene: COL4A5 were set to
Proteinuric renal disease v1.93 COL4A4 Eleanor Williams Publications for gene: COL4A4 were set to
Proteinuric renal disease v1.92 COL4A3 Eleanor Williams Phenotypes for gene: COL4A3 were changed from to Alport syndrome, autosomal dominant #104200; Alport syndrome, autosomal recessive #203780; Hematuria, benign familial #141200
Proteinuric renal disease v1.91 COL4A3 Eleanor Williams Publications for gene: COL4A3 were set to
Proteinuric renal disease v1.90 CLCN5 Eleanor Williams Publications for gene: CLCN5 were set to
Proteinuric renal disease v1.89 ACTN4 Eleanor Williams Phenotypes for gene: ACTN4 were changed from to Glomerulosclerosis, focal segmental, 1 603278
Proteinuric renal disease v1.88 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706; 29043128
Proteinuric renal disease v1.87 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706; 29043128
Proteinuric renal disease v1.86 ACTN4 Eleanor Williams Publications for gene: ACTN4 were set to PubMed: 10700177; 26301083; J Am Soc Nephrol 16: 3694–3701, 2005. doi: 10.1681/ASN.2005070706
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Classified gene: FAT1 as Green List (high evidence)
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there is sufficient pedigrees and strong enough functional data to rate this gene green.
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Gene: fat1 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.84 FAT1 Eleanor Williams commented on gene: FAT1: After consultation with the GMS Renal Specialist Test group and comment from Moin Saleem, it was decided that there were enough patients from different pedigrees with nephrotic range proteinuria with rare FAT1 variants compatible with AR inheritance and that the biology is strong, as the KO mice get very severe nephrosis, and expression at the podocyte slit diaphragm, so that this gene should be rated green.
Proteinuric renal disease v1.84 TNS2 Eleanor Williams Phenotypes for gene: TNS2 were changed from to nephrotic syndrome
Proteinuric renal disease v1.83 TNS2 Eleanor Williams Publications for gene: TNS2 were set to
Proteinuric renal disease v1.82 TNS2 Eleanor Williams Mode of inheritance for gene: TNS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.81 TNS2 Eleanor Williams Classified gene: TNS2 as Green List (high evidence)
Proteinuric renal disease v1.81 TNS2 Eleanor Williams Added comment: Comment on list classification: Rating green as there are 4 unrelated families (plus another with possible founder mutation in common with one of the 4) with variants in this gene and a relevant phenotype.
Proteinuric renal disease v1.81 TNS2 Eleanor Williams Gene: tns2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.80 TNS2 Eleanor Williams commented on gene: TNS2: No association with any phenotype in OMIM or Gene2Phenotype.

PMID : 29773874 - Ashraf et al 2018 - homozygosity mapping combined with whole exome sequencing in multiple families with Nephrotic syndrome. TNS2 variants found in 5 families (1 Turkish, 1 European, 1 Nigerian, 2 Indian). 3 families showed homozygous variants, 2 compound heterozygous. One Indian family was homozygous for a c.2574C>G
p.Ile858Met variant. The other Indian family was compound heterozygous for this variant and another c.1693C>T p.Arg565Trp suggesting that the c.2574C>G variant may be a founder allele. Altered amino acid residues were well conserved throughout evolution
Proteinuric renal disease v1.80 TBC1D8B Eleanor Williams Phenotypes for gene: TBC1D8B were changed from to Steroid-resistant nephrotic syndrome
Proteinuric renal disease v1.79 TBC1D8B Eleanor Williams Publications for gene: TBC1D8B were set to
Proteinuric renal disease v1.78 TBC1D8B Eleanor Williams Added comment: Comment on mode of inheritance: PMID: 30661770 - 2 carrier (heterozygous) females in family A developed proteinuria at age 7 and as an adult (later than males).
Proteinuric renal disease v1.78 TBC1D8B Eleanor Williams Mode of inheritance for gene: TBC1D8B was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.77 TBC1D8B Eleanor Williams Mode of inheritance for gene: TBC1D8B was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuric renal disease v1.76 TBC1D8B Eleanor Williams Classified gene: TBC1D8B as Green List (high evidence)
Proteinuric renal disease v1.76 TBC1D8B Eleanor Williams Added comment: Comment on list classification: 2 unrelated families plus functional evidence
Proteinuric renal disease v1.76 TBC1D8B Eleanor Williams Gene: tbc1d8b has been classified as Green List (High Evidence).
Proteinuric renal disease v1.75 TBC1D8B Eleanor Williams edited their review of gene: TBC1D8B: Added comment: Not listed in OMIM or Gene2Phenotype

PMID: 30661770 - Dorval et al 2019 - by exome sequencing, they identified missense mutations (c.738G>C and c.872T>C) in TBC1D8B in two families with an X-linked early-onset SRNS with FSGS. Immunofluorescence studies revealed TBC1D8B presence in human glomeruli, and affected individual podocytes displayed architectural changes associated with migration defects commonly found in FSGS. In zebrafish they demonstrated that both knockdown and knockout of the unique TBC1D8B ortholog-induced proteinuria and that this phenotype was rescued by human TBC1D8B mRNA injection, but not by either of the two mutated mRNAs. They also showed an interaction between TBC1D8B and Rab11b, a key protein in vesicular recycling in cells.

Family A (Ecuador) - affected females (I-2 and II-2) exhibited non-nephrotic proteinuria, while affected boys (II-1, II-3, and II-4) developed congenital or early-onset NS. Family B (UK) - sporadic SRNS-affected individual (II-2) in family B. The affected individual (II-2), a male from European ancestry presenting with early-onset SRNS at the age of 2 years, had no other systemic features. Both mutations segregated with the affected status in the respective families and were, respectively, present in 1/27,314 (with no hemizygous) and absent from gnomAD database in the population-matched control subjects.; Changed publications: PMID: 30661770
Proteinuric renal disease v1.75 PAX2 Eleanor Williams Phenotypes for gene: PAX2 were changed from to Glomerulosclerosis, focal segmental, 7 #616002
Proteinuric renal disease v1.74 PAX2 Eleanor Williams Publications for gene: PAX2 were set to
Proteinuric renal disease v1.73 PAX2 Eleanor Williams Mode of inheritance for gene: PAX2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Proteinuric renal disease v1.72 PAX2 Eleanor Williams Classified gene: PAX2 as Green List (high evidence)
Proteinuric renal disease v1.72 PAX2 Eleanor Williams Added comment: Comment on list classification: > 3 cases where variants in this gene are associated with a relevant phenotype
Proteinuric renal disease v1.72 PAX2 Eleanor Williams Gene: pax2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.71 PAX2 Eleanor Williams commented on gene: PAX2: PAX2 is associated with Glomerulosclerosis, focal segmental, 7 (616002) and Papillorenal syndrome (120330) in OMIM.

OMIM list numerous cases of PAX2 variants in patients with Papillorenal Syndrome/Renal coloboma syndrome and with focal segmental glomerulosclerosis-7.

PMID: 26571382 - Okumura et al 2015 - 26 patients with Renal coloboma syndrome were screened. Patients with CHARGE, COACH and Jouberts syndrome were excluded. Analyzed the sequences of PAX2 and 25 other genes in 26 patients clinically diagnosed with RCS, and 4 optic nerve coloboma only patients as disease-negative controls. Six PAX2 mutations (3 frameshifts, 1 nonsense, 2 missense) in 11 probands; two in family cohorts [n = 5 and n = 2] and in 4 out of 19 patients with sporadic disease, including four novel mutations, were confirmed using Sanger sequencing.
Proteinuric renal disease v1.71 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from to LOWE OCULOCEREBRORENAL SYNDROME #309000; Dent disease 2 #300555
Proteinuric renal disease v1.70 OCRL Eleanor Williams Publications for gene: OCRL were set to
Proteinuric renal disease v1.69 OCRL Eleanor Williams Mode of inheritance for gene: OCRL was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.68 OCRL Eleanor Williams Classified gene: OCRL as Green List (high evidence)
Proteinuric renal disease v1.68 OCRL Eleanor Williams Added comment: Comment on list classification: More than three families have variants in OCRL and a disease phenotype.
Proteinuric renal disease v1.68 OCRL Eleanor Williams Gene: ocrl has been classified as Green List (High Evidence).
Proteinuric renal disease v1.67 OCRL Eleanor Williams edited their review of gene: OCRL: Added comment: Associated with Dent disease 2 (300555) and Lowe syndrome (309000) in OMIM.

PMID: 21249396 - Tasic et al 2011 - 5 unrelated Macedonian patients with 4 different variants in OCRL. 2 diagnosed with Lowe Syndrome (both with LMWP and hypercalciuria) and 3 with Dent disease 2 (all with asymptomatic proteinuria). All five patients had LMWP and hypercalciuria/


PMID: 17384968 - Sekine et al 2007 - 3 distinct OCRL1 mutations in 3 patients with the Dent disease phenotype are described. All the patients manifested an extremely high degree of low-molecular-weight proteinuria and showed no ocular abnormalities or apparent mental retardation. Urinalysis and blood chemistry showed no findings suggestive of Fanconi syndrome with renal tubular acidosis. Mutations in CLCN5 were ruled out. The mutations identified in OCRL1 are one frame-shift mutation (I127stop) and two missense mutations (R301C and R476W).

PMID: 27625797 - Böckenhauer et al 2012 - 14 CLCN5-negative patients from 12 families with a phenotype resembling Dent disease were assessed for defects in OCRL. In six of these kindreds three novel (c.149+1G>A, c.1126A>T, c.1547T>C) and three repeatedly observed mutations (c.166_167delTT, c.901C>T, c.1426C>T) were discovered. All showed low molecular weight proteinuria.; Changed publications: PMID: 21249396, PMID: 17384968; Changed phenotypes: LOWE OCULOCEREBRORENAL SYNDROME #309000, Dent disease 2 #300555
Proteinuric renal disease v1.67 NUP85 Eleanor Williams Publications for gene: NUP85 were set to
Proteinuric renal disease v1.66 NUP85 Eleanor Williams Phenotypes for gene: NUP85 were changed from to Nephrotic syndrome, type 17 #618176
Proteinuric renal disease v1.65 NUP85 Eleanor Williams Mode of inheritance for gene: NUP85 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.64 NUP85 Eleanor Williams Classified gene: NUP85 as Green List (high evidence)
Proteinuric renal disease v1.64 NUP85 Eleanor Williams Added comment: Comment on list classification: 3 families with SRNS and variants in NUP85.
Proteinuric renal disease v1.64 NUP85 Eleanor Williams Gene: nup85 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.63 NUP85 Eleanor Williams commented on gene: NUP85: In OMIM this gene is associated with Nephrotic syndrome, type 17 (618176).

PMID: 30179222 - Braun et al 2018 - 4 individuals from 3 unrelated families with SRNS (families A5195, A3259, and NCR3227/3310) were found to have variants in NUP85 by high-throughput exon sequencing. Two mutations were homozygous missense mutations (c.1430C>T, p.Ala477Val, and c.1933C>T, p.Arg645Trp). One family (NCR3227/3310) carried 2 compound heterozygous alleles (c.405+1G>A and c.1741G>C, p.Ala581Pro), which segregated from the maternal and the paternal side, respectively. All families had SRNS and microscopic hematuria. Family NCR3227/3310 additionally displayed intellectual disability, but showed no structural brain defects.

Functional data - morpholino knockdown of nup85 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP85 in podocytes activated Cdc42, an important effector of SRNS pathogenesis.
Proteinuric renal disease v1.63 ITSN1 Eleanor Williams Phenotypes for gene: ITSN1 were changed from to Early childhood SSNS
Proteinuric renal disease v1.62 ITSN1 Eleanor Williams Publications for gene: ITSN1 were set to
Proteinuric renal disease v1.61 ITSN1 Eleanor Williams Mode of inheritance for gene: ITSN1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.60 ITSN1 Eleanor Williams Classified gene: ITSN1 as Green List (high evidence)
Proteinuric renal disease v1.60 ITSN1 Eleanor Williams Added comment: Comment on list classification: 3 families with variants in this gene and a nephrotic syndrome phenotype
Proteinuric renal disease v1.60 ITSN1 Eleanor Williams Gene: itsn1 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.59 ITSN1 Eleanor Williams commented on gene: ITSN1: Not associated with any phenotype in OMIM but last update was in 2007

PMID: 29773874 - Ashraf et al 2018 - 3 unrelated families with rare ITSN1 variants and SRNS/CNS or SSNS. Using HM and WES in two siblings of Arab family A3706 with early-onset NS they identified a homozygous missense mutation of ITSN1 at a highly conserved amino acid residue (p.Pro180Ser). By high-throughput sequencing, they identified two additional families (A977 and A2274) with four additional compound heterozygous missense mutations of ITSN1.
Proteinuric renal disease v1.59 FAT1 Eleanor Williams Phenotypes for gene: FAT1 were changed from to Glomerulotubular nephropathy
Proteinuric renal disease v1.58 FAT1 Eleanor Williams Publications for gene: FAT1 were set to
Proteinuric renal disease v1.57 FAT1 Eleanor Williams Mode of inheritance for gene: FAT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.56 FAT1 Eleanor Williams commented on gene: FAT1: Not associated with any phenotype in OMIM.

PMID: 26905694 - Gee et al 2016. 4 families reported with a variant in FAT1. 27 known genes previously linked to SRNS were screened in these individuals, but no explanatory mutations were detected. All affected individuals exhibited a glomerulotubular nephropathy of SRNS, tubular ectasia and microscopic haematuria among other phenotypes.

Family 1 - A4623, a Turkish boy from consanguineous parents with intellectual disability, pulmonary artery stenosis and bilateral blepharoptosis in early childhood, admitted to the hospital at age 15 years because of proteinuria and haematuria. Kidney biopsy showed a glomerulotubular nephropathy. Following WES and filtering of variants from normal reference sequence, 3 rare variants in FAT1, PIDD and DZIP1 remained. The variant in the FAT1 gene, is a homozygous protein truncating mutation (c.3093_3096del, p.P1032Cfs*11). This variant is classified as a VUS in OMIM.

Family 2 One child of Arab origin (A3027) presented with proteinuria and haematuria. A3027 was diagnosed with Ewing sarcoma, and lung and spinal metastasis at the age of 15 years. Following variant filtering by HM and WES, two rare missense variants in FAT1 and EHD1 remained . Mutations in the 27 known SRNS genes were excluded by evaluation of the WES data. The variant (c.857A>F;p.N286S) in FAT1 is reported as a SNP in the dbSNP database, however, its minor allele frequency is 0.0002 and it never occurred in the homozygous state. The FAT1 variant alters an amino-acid residue conserved throughout evolution down to Drosophila melanogaster.

Families 3 and 4 - When performing highly parallel sequencing of all FAT1 exons in 1,500 additional individuals with features of NS and 800 individuals with features of tubulointerstitial nephroapathy, we detected in 2 additional families. . In a female African-American girl (A789) from non-consanguineous parents, another compound-heterozygous mutation was detected (c.3008C>T, p.A1003V and c.9259C>G, p. R3087G). Further information was not available and segregation analysis was not performed since the girl was lost for follow-up. A3507, an African girl from non-consanguineous parents, showed haematuria and proteinuria at the age of 2 years. One of the compound-heterozygous mutation (c.4517G>A, p.R1506H) was detected in her mother, but not the other. DNA from the father was not available.

Functional studies indicate an absence of FAT1 in patient fibroblasts (from family 1) and decreased migration rates compared to controls. Knockdown of FAT1 in differentiated podocytes showed similarly decreased migration rates, which were associated with decreased active RAC1 and CDC42, implicating a defect in RHO GTPase signaling in the pathogenesis.
Proteinuric renal disease v1.56 EMP2 Eleanor Williams Phenotypes for gene: EMP2 were changed from steroid sensitive nephrotic syndrome to steroid sensitive nephrotic syndrome; Nephrotic syndrome, type 10 #615861
Proteinuric renal disease v1.55 EMP2 Eleanor Williams Classified gene: EMP2 as Green List (high evidence)
Proteinuric renal disease v1.55 EMP2 Eleanor Williams Added comment: Comment on list classification: 3 families with variants in this gene which segregate with the condition, plus some functional data.
Proteinuric renal disease v1.55 EMP2 Eleanor Williams Gene: emp2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.54 EMP2 Eleanor Williams commented on gene: EMP2: Associated with Nephrotic syndrome, type 10 615861 in OMIM.

PMID 24814193 - Gee et al 2014 - performed homozygosity mapping, whole-exome sequencing, and multiplex PCR followed by next-generation sequencing. They found biallelic mutations in EMP2 (epithelial membrane protein 2) in four individuals from three unrelated families affected by SRNS or SSNS. Consanguineous Turkish family A1679 had a homozygous truncating variant (c.184C>T [p.Gln62∗]) in EMP2 which segregated in the condition. In another Turkish family (A150) the affected individual was compound heterozygous for 2 variants in EMP2 - 21C>G, p.Phe7Leu and
c.184C>T, p.Gln62∗. In a third African-American family (A4601) the proband was homozygous for a missense mutation c.28G>A, p.Ala10Thr. All mutations were absent from >190 ethnically matched healthy control individuals and from >8,600 European control individuals in the NHLBI EVS

Functional studies showed that EMP2 exclusively localized to glomeruli in the kidney. Knockdown of emp2 in zebrafish resulted in pericardial effusion, supporting the pathogenic role of mutated EMP2 in human NS. Knockdown of EMP2 in podocytes and endothelial cells resulted in an increased amount of CAVEOLIN-1 and decreased cell proliferation.
Proteinuric renal disease v1.54 DLC1 Eleanor Williams Phenotypes for gene: DLC1 were changed from to Childhood and adult SSNS and SRNS
Proteinuric renal disease v1.53 DLC1 Eleanor Williams Publications for gene: DLC1 were set to
Proteinuric renal disease v1.52 DLC1 Eleanor Williams Mode of inheritance for gene: DLC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.51 DLC1 Eleanor Williams Classified gene: DLC1 as Red List (low evidence)
Proteinuric renal disease v1.51 DLC1 Eleanor Williams Added comment: Comment on list classification: Plausible disease causing variants found in more than 3 cases.
Proteinuric renal disease v1.51 DLC1 Eleanor Williams Gene: dlc1 has been classified as Red List (Low Evidence).
Proteinuric renal disease v1.50 DLC1 Eleanor Williams commented on gene: DLC1: In OMIM this gene is only associated with Colorectal cancer, somatic, not a relevant phenotype.

PMID: 29773874 -performed homozygosity mapping combined with whole exome sequencing in multiple families with Nephrotic Syndrome. Also performed high-throughput exon sequencing in a worldwide cohort of ~1000 additional families with NS, examining specific candidate genes for NS based on genetic mouse models of NS. We identified recessive mutations of DLC1 in 4 families with NS. 6 different variants. Two individuals were compound heterozygous, two were homozygous. Families of different ethnicities.
Proteinuric renal disease v1.50 CRB2 Eleanor Williams Phenotypes for gene: CRB2 were changed from steroid resistant nephrotic syndrome to steroid resistant nephrotic syndrome; Focal segmental glomerulosclerosis 9 #616220; Ventriculomegaly with cystic kidney disease #219730
Proteinuric renal disease v1.49 CRB2 Eleanor Williams Publications for gene: CRB2 were set to 25557779; 27942854
Proteinuric renal disease v1.48 CRB2 Eleanor Williams Classified gene: CRB2 as Green List (high evidence)
Proteinuric renal disease v1.48 CRB2 Eleanor Williams Added comment: Comment on list classification: > 3 unrelated cases with plausible disease causing variants in this gene.
Proteinuric renal disease v1.48 CRB2 Eleanor Williams Gene: crb2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.47 CRB2 Eleanor Williams edited their review of gene: CRB2: Added comment: Associated with Focal segmental glomerulosclerosis 9 (616220) and Ventriculomegaly with cystic kidney disease (219730) in OMIM.

PMID: 25557779 - Ebarasi et al 2015 - recessive CRB2 variants were detected in 4 unrelated families (2 from Turkey, 2 from Europe). 3 families had parental consanguinity and were homozygous for the variants. In the other family compound heterozgyous variants in CRB2 were detected. Mutations in the first 2 families were found by homozygosity mapping and/or whole-exome sequencing; mutations in the second 2 families were found by sequencing the CRB2 gene in 1,010 families with steroid-resistant nephrotic syndrome. 3 of the mutations occurred at highly conserved residues in the tenth EGF-like domain; and functional studies showed that in crb2-null zebrafish 2 of these mutations resulted in loss of protein function.

PMID: 27942854 - Udagawa et al 2017 - Whole exome sequencing was performed in a 3-year-old girl with SRNS and identified novel compound heterozygous mutations in exons 10 and 12 of CRB2 (p.Trp1086ArgfsX64 and p.Asn1184Thr). Renal pathology showed focal segmental glomerulosclerosis with effaced podocyte foot processes in a small area, with significantly decreased Crb2 expression

PMID: 29473663 - Watanabe et al 2018 - report the long-term clinicopathologic observation of a Japanese female patient with SRNS caused by a newly identified compound heterozygous mutation of CRB2 (p.Arg628Cys and p.Gly839Trp).; Changed publications: PMID: 25557779, PMID: 29473663; Changed phenotypes: Focal segmental glomerulosclerosis 9 #616220, Ventriculomegaly with cystic kidney disease #219730
Proteinuric renal disease v1.47 COQ8B Eleanor Williams Phenotypes for gene: COQ8B were changed from to Nephrotic syndrome, type 9 #615573
Proteinuric renal disease v1.46 COQ8B Eleanor Williams Publications for gene: COQ8B were set to
Proteinuric renal disease v1.45 COQ8B Eleanor Williams Mode of inheritance for gene: COQ8B was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.44 COQ8B Eleanor Williams Classified gene: COQ8B as Green List (high evidence)
Proteinuric renal disease v1.44 COQ8B Eleanor Williams Added comment: Comment on list classification: >3 families with plausible disease causing variants in COQ8B.
Proteinuric renal disease v1.44 COQ8B Eleanor Williams Gene: coq8b has been classified as Green List (High Evidence).
Proteinuric renal disease v1.43 COQ8B Eleanor Williams commented on gene: COQ8B: Associated with Nephrotic syndrome, type 9 615573 in OMIM. Previous symbol: ADCK4.

PMID: 24270420 - Ashraf et al 2013 - using a combination of homozygosity mapping and whole human exome resequencing, identified variants in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. Several different variants. Functional data supports the role of this gene's involvement in nephrotic syndrome-associated phenotypes. In human podocytes, ADCK4 interacted with members of the CoQ10 biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7.
Proteinuric renal disease v1.43 PODXL Eleanor Williams Phenotypes for gene: PODXL were changed from to Congenital nephrotic syndrome
Proteinuric renal disease v1.42 PODXL Eleanor Williams Publications for gene: PODXL were set to
Proteinuric renal disease v1.41 PODXL Eleanor Williams Mode of inheritance for gene: PODXL was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v1.40 PODXL Eleanor Williams Classified gene: PODXL as Green List (high evidence)
Proteinuric renal disease v1.40 PODXL Eleanor Williams Added comment: Comment on list classification: 2 cases with functional evidence that the variants may cause disease.
Additional case of patient with SRNS where variant is predicted to be deleterious. 1 case with a variant in an individual with FSGS but no evidence variant affects protein function.

A further case with a patient with compound heterozygous variants in PDXL and congenital nephrotic syndrome.
Proteinuric renal disease v1.40 PODXL Eleanor Williams Gene: podxl has been classified as Green List (High Evidence).
Proteinuric renal disease v1.39 PODXL Eleanor Williams edited their review of gene: PODXL: Added comment: PMID: 30523047 - Lin et al 2019 - heterozygous nonsense PODXL mutations in two unrelated pedigrees: c.C976T (p. Arg326X) in a Chinese pedigree that was associated with proteinuria and renal insufficiency, and c.C1133G (p. Ser378X) in a British–Indian AD-FSGS pedigree. They also provide evidence with in vitro study showing that the heterozygous nonsense PODXL mutations may be causative in AD-FSGS.

PMID: 29244787 - Kang et al 2017 - report a patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL. The 2 variants were a missense mutation at the initiation codon c.3G>T (p.Met1Ile) and a nonsense mutation at c.1023G>A (p.Trp341Ter).

PMID: 28117080 - Bierzynska et al 2017 - Whole exome sequencing was performed on 187 paediatric patients with Steroid Resistant Nephrotic Syndrome (SRNS). 1 case found with variant in PODXL c.1427A>T:p.His476Leu which is predicted to be deleterious.

PMID: 24048372 - Barua et al 2014 - exome sequencing of affected cousins from an autosomal dominant pedigree with FSGS identified a cosegregating private variant, PODXL p.L442R. However, this change does not alter protein stability, extracellular domain glycosylation, cell surface expression, global subcellular localization, or interaction with its intracellular binding partner ezrin.; Changed publications: PMID: 30523047, PMID: 29244787; Changed phenotypes: Congenital nephrotic syndrome
Proteinuric renal disease v1.39 NUP107 Eleanor Williams Phenotypes for gene: NUP107 were changed from to Nephrotic syndrome, type 11 #616730
Proteinuric renal disease v1.38 NUP107 Eleanor Williams Publications for gene: NUP107 were set to
Proteinuric renal disease v1.37 NUP107 Eleanor Williams Mode of inheritance for gene: NUP107 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.36 NUP107 Eleanor Williams Classified gene: NUP107 as Green List (high evidence)
Proteinuric renal disease v1.36 NUP107 Eleanor Williams Added comment: Comment on list classification: 3 families with variants in this gene.
Proteinuric renal disease v1.36 NUP107 Eleanor Williams Gene: nup107 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.35 NUP107 Eleanor Williams commented on gene: NUP107: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that although it is clearly rare with no variants found in >600 cases in Bristol, it is appropriate for inclusion in the panel.
Proteinuric renal disease v1.35 NUP107 Eleanor Williams edited their review of gene: NUP107: Added comment: Associated with Galloway-Mowat syndrome 7 (618348) and Nephrotic syndrome, type 11 (616730) in OMIM.

PMID: 26411495 - Miyake et al 2015 - biallelic NUP107 mutations in nine affected individuals who are from five unrelated families and show early-onset steroid-resistant nephrotic syndrome (SRNS). All individuals were compound heterozgyous, and all had a c.2492A>C (p.Asp831Ala) variant in common. This variant, c.2492A>C, was observed at a frequency of 0.0013587 only in HGVD, but not in the EVS, ExAC Browser, or in-house Japanese exome database. Three other variants were found in addition - c.469G>T (p.Asp157Tyr),c.969+1G>A (splice site) and c.1079_1083delAAGAG (p.Glu360Glyfs∗6).

PMID: 30179222 - Braun et al 2018 - homozgyous or compound heterozygous variants found in 7 families with SRNS.. The same homozygous missense mutation (c.303G>A, p.Met101Ile) in NUP107 was detected 5 consanguineous families with SRNS and represents a South Asian founder allele. They also detected a homozygous missense mutation of NUP107 (c.2666A>G, p.Tyr889Cys) in family A3825 and 2 compound heterozygous alleles (c.1021dup, p.Glu341Glyfs*3, and c.2129_2131delAAG, p.Glu710del) of NUP107 in family A1830.; Changed publications: PMID: 26411495, PMID 30179222
Proteinuric renal disease v1.35 DHFR Eleanor Williams edited their review of gene: DHFR: Added comment: After checking with Elizabeth Watson, it was concluded that this gene was rating initially green in error. There is no evidence to support its inclusion on this panel.; Changed rating: RED
Proteinuric renal disease v1.35 ARHGDIA Eleanor Williams commented on gene: ARHGDIA: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that although it is clearly rare with no variants found in >600 cases in Bristol, it is appropriate for inclusion in the panel.
Proteinuric renal disease v1.35 ITGA3 Eleanor Williams commented on gene: ITGA3: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that this gene should be rated green on this panel.
Proteinuric renal disease v1.35 MAGI2 Eleanor Williams Phenotypes for gene: MAGI2 were changed from to Nephrotic syndrome, type 15 617609
Proteinuric renal disease v1.34 MAGI2 Eleanor Williams Publications for gene: MAGI2 were set to
Proteinuric renal disease v1.33 MAGI2 Eleanor Williams Mode of inheritance for gene: MAGI2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.32 MAGI2 Eleanor Williams Classified gene: MAGI2 as Green List (high evidence)
Proteinuric renal disease v1.32 MAGI2 Eleanor Williams Added comment: Comment on list classification: Rating green as there are 4 cases reported.
Proteinuric renal disease v1.32 MAGI2 Eleanor Williams Gene: magi2 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.31 MAGI2 Eleanor Williams commented on gene: MAGI2: Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that although the reported cases have slightly different phenotypes, these are sufficiently similar to have the same pathophysiological basis. Bristol also have some unpublished cases.
Proteinuric renal disease v1.31 MAGI2 Eleanor Williams edited their review of gene: MAGI2: Added comment: Associated with Nephrotic syndrome, type 15 (617609) in OMIM.

PMID: 29773874 - Ashraf et al 2018 - identified homozygous truncating mutations in the MAGI2 gene (p.Gly39* and p.Tyr746*) in two individuals from unrelated families with SRNS and neurologic impairment.

PMID: 27932480 - Bierzynska et al 2017 - detected two unique frameshift mutations and one duplication in three patients (two families); Two siblings (175 and 175S) shared the same homozygous frameshift deletion c.3998delG:p.(Gly1333Alafs*141). The patient with the sporadic case (180) exhibited compound heterozygosity: a deletion (paternal) resulting in a premature stop codon c.64_71delAGGAACCC:p.(Arg22Glyfs*7) together with a duplication (maternal) c.3526_3533dupCTGGCAGA:p.(Glu1178Aspfs*9). All three variants were absent in the ExAC database.; Changed publications: PMID: 29773874, PMID: 27932480
Proteinuric renal disease v1.31 GLA Eleanor Williams Publications for gene: GLA were set to
Proteinuric renal disease v1.30 GLA Eleanor Williams Phenotypes for gene: GLA were changed from to Fabry disease 301500
Proteinuric renal disease v1.29 GLA Eleanor Williams Mode of inheritance for gene: GLA was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.28 GLA Eleanor Williams Classified gene: GLA as Amber List (moderate evidence)
Proteinuric renal disease v1.28 GLA Eleanor Williams Added comment: Comment on list classification: Rating Amber until a review of the prevalence of proteinuria in Fabry disease patients is done.
Proteinuric renal disease v1.28 GLA Eleanor Williams Gene: gla has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v1.27 GLA Eleanor Williams commented on gene: GLA: Proteinuria is a feature of Fabry disease, but the GMS renal specialist test group will review how common proteinuria is in patients with this syndrome. Rating Amber for now.
Proteinuric renal disease v1.27 GLA Eleanor Williams commented on gene: GLA: GLA is associated with Fabry disease (301500) in OMIM with numerous cases reported.
Proteinuric renal disease v1.27 WDR73 Eleanor Williams edited their review of gene: WDR73: Added comment: WDR73 is associated with Galloway-Mowat syndrome 1 (251300) in OMIM.

Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of Galloway-Mowat syndrome, and WDR73 should be included on the Proteinuric renal disease panel.

PMID: 26123727 - Vodopiutz et al 2015. Report 2 patients from unrelated consanguineous families diagnosed with Galloway-Mowat syndrome. One with Indian one with Turkish ethnicity. Two variants identified, one missense, the other truncating; c.287G>A p.(Arg96Lys) and c.940C>T p.(Gln314*).

PMID: 25466283 - Colin et al 2014. Report 2 families with children with Galloway-Mowat syndrome. In family A (Moroccan) there are two affected children. One developed proteinuria, the other did not (at age 7). A homozygous A nonsense WDR73 mutation (c.129T>G [p.Tyr43∗]) was identified. In family B (consanguineous Turkish family) with one affected child who showed proteinuria as part of the phenotype, they detected another homozygous frameshift mutation in WDR73 (c.766dupC [p.Arg256Profs∗18]). Both variants segregated with the disease in the families, and neither is referenced in the NHLBI Exome Variant Server or in dbSNP.

PMID: 25873735 - Ben-Omran et al. (2015) - In 2 sisters, born of consanguineous Arab parents, with GAMOS1, identified a homozygous truncating mutation in the WDR73 gene (Q235X). One sister had proteinuria and other findings are suggestive of nephrotic disease (age 11 years), and the other sister at age 5 had findings suggestive of early features that might progress towards nephrotic disease.

PMID: 26070982 - Jinks et al. (2015) - report 27 Amish patients with GAMOS1 and identified a homozygous truncating mutation in the WDR73 gene. 57% developed steroid non-responsive, fluctuating proteinuria.; Changed publications: PMID: 26123727, PMID: 25466283
Proteinuric renal disease v1.27 TP53RK Eleanor Williams Phenotypes for gene: TP53RK were changed from to Galloway-Mowat syndrome 4 #617730
Proteinuric renal disease v1.26 TP53RK Eleanor Williams Publications for gene: TP53RK were set to
Proteinuric renal disease v1.25 TP53RK Eleanor Williams Mode of inheritance for gene: TP53RK was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.24 TP53RK Eleanor Williams Classified gene: TP53RK as Green List (high evidence)
Proteinuric renal disease v1.24 TP53RK Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as there are 3 unrelated families with variants in this gene with Galloway-Mowatt syndrome.
Proteinuric renal disease v1.24 TP53RK Eleanor Williams Gene: tp53rk has been classified as Green List (High Evidence).
Proteinuric renal disease v1.23 TP53RK Eleanor Williams commented on gene: TP53RK: TP53RK is associated with Galloway-Mowat syndrome 4 (617730) in OMIM.

Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of Galloway-Mowat syndrome, and TP53RK should be included on the Proteinuric renal disease panel.

PMID: 28805828 - Braun et al 2017 - 4 patients from 3 unrelated families with Galloway-Mowat syndrome-4. Compound heterozygous or homozygous variants (4 different variants) found in the TP53RK gene. Functional data suggests the variants impaired protein functionality.
Proteinuric renal disease v1.23 NUP133 Eleanor Williams Phenotypes for gene: NUP133 were changed from to ?Galloway-Mowat syndrome 8 618349; Nephrotic syndrome, type 18 618177
Proteinuric renal disease v1.22 NUP133 Eleanor Williams Publications for gene: NUP133 were set to
Proteinuric renal disease v1.21 NUP133 Eleanor Williams Mode of inheritance for gene: NUP133 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.20 NUP133 Eleanor Williams edited their review of gene: NUP133: Added comment: This gene has a provisional association with ?Galloway-Mowat syndrome 8 (618349) and an association with Nephrotic syndrome, type 18 (618177) in OMIM.

Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of this condition, and NUP133 should be included on the Proteinuric renal disease panel.

PMID: 30179222 - Braun et al. (2018) - 2 families with nonsyndromic SRNS. In consanguineous family F797-21 they identified a homozygous (c.2922T>G, p.Ser974Arg) variant in 1 patient, and in a second family they identified compound heterozygous missense mutations (c.691C>G, p.Arg231Gly, and c.3164T>C, p.Leu1055Ser) in two siblings (A2174-21 and A2174-22).

PMID: 30427554 - Fujita et al (2018) - identified a homozygous NUP133 mutation, c.3335-11T>A, which results in the insertion of 9bp of intronic sequence between exons 25 and 26 in the mutant transcript. A nup133-knockdown zebrafish model exhibited microcephaly, fewer neuronal cells, underdeveloped glomeruli, and fusion of the foot processes of the podocytes, which mimicked human GAMOS features. nup133 morphants could be rescued by human wild-type NUP133 mRNA but not by mutant mRNA; Changed publications: PMID: 30179222
Proteinuric renal disease v1.20 LAGE3 Eleanor Williams Phenotypes for gene: LAGE3 were changed from to Galloway-Mowat syndrome 2, X-linked #301006
Proteinuric renal disease v1.19 LAGE3 Eleanor Williams Publications for gene: LAGE3 were set to
Proteinuric renal disease v1.18 LAGE3 Eleanor Williams Mode of inheritance for gene: LAGE3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuric renal disease v1.17 LAGE3 Eleanor Williams Classified gene: LAGE3 as Green List (high evidence)
Proteinuric renal disease v1.17 LAGE3 Eleanor Williams Added comment: Comment on list classification: Changing this gene from red to green as 3 unrelated cases of variants in this gene in patients with Galloway-Mowat syndrome have been reported.
Proteinuric renal disease v1.17 LAGE3 Eleanor Williams Gene: lage3 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.16 LAGE3 Eleanor Williams commented on gene: LAGE3: LAGE3 is associated with Galloway-Mowat syndrome 2, X-linked (#301006) in OMIM. Following discussion with some members of the GMS Renal Specialist Test group on 2019-03-22 it was agreed that proteinuria is a relevant feature of this condition, and LAGE3 should be included on the Proteinuric renal disease panel.

PMID: 28805828 - Braun et al 2017 - hemizygous mutations in the LAGE3 gene were identified ion 4 male patients from 3 unrelated families with X-linked Galloway-Mowat syndrome-2. Three different variants (2 missense, one splice site). Patients with different ethnic backgrounds.
Proteinuric renal disease v1.16 ARHGDIA Eleanor Williams edited their review of gene: ARHGDIA: Added comment: PMID: 23434736 - Gupta et al 2013 - 2 sisters with congenital nephrotic syndrome who were born to consanguineous parents of Pakistani origin. Using whole exome sequencing, they found both girls have a homozygous in-frame deletion in ARHGDIA, c.553_555del(p.Asp185del). The healthy mother was found to be a heterozygous carrier for this deletion. The father's DNA was unavailable for analysis. Functional studies showed that RhoGDIα protein was strongly expressed in the glomerulus of the adult mouse kidney and that normal binding of mutant protein was impaired.

PMID: 23867502 - Gee et al 2013 - performed homozygosity mapping and then whole exome resequencing in a family of Ashkenazi Jewish origin in whom 2 siblings had early-onset SRNS with renal histology of diffuse mesangial sclerosis. They found in both siblings a homozygous missense mutation (c.518G>T;p.G173V) of ARHGDIA. They then examined 65 additional individuals with DMS and 350 individuals with SRNS, we detected a homozygous mutation (c.358C>T;p.R120X) in an infant (Moroccan) with congenital NS. Functional studies showed both mutant protein had abrogated interaction with RHO GTPases and the nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish.

PMID: 30295827 - Schapiro et al 2019 - screen for 11 AS, aHUS and thrombotic thrombocytopenic purpura-causing genes by exon sequencing and 23 SRNS-causing genes by WES or high-throughput exon sequencing in an international cohort of 371 patients from 362 families presenting with both proteinuria and hematuria before age 25 years. This screen included ARHGDIA. 1 consangineious Jewish family with 2 individuals are homozgous for c.518G>T, p.Gly173Val.

Summary - 4 families with 3 different variants reported. The two Jewish families have the same variant. Functional evidence that the protein is expressed in the kidney and that the function of mutant protein is impared.; Changed publications: 23434736, 23867502, 30295827
Proteinuric renal disease v1.16 XPO5 Eleanor Williams reviewed gene: XPO5: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 26878725; Phenotypes: Nephrotic syndrome ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 SLC19A3 Eleanor Williams reviewed gene: SLC19A3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) #607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 SLC19A2 Eleanor Williams reviewed gene: SLC19A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome #249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 NXF5 Eleanor Williams reviewed gene: NXF5: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 23686279; Phenotypes: FSGS and heart-block disorder; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Proteinuric renal disease v1.16 NLRP3 Eleanor Williams reviewed gene: NLRP3: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 30431487; Phenotypes: SRNS; Mode of inheritance:
Proteinuric renal disease v1.16 NEU1 Eleanor Williams reviewed gene: NEU1: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 30450471; Phenotypes: SRNS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 NEIL1 Eleanor Williams reviewed gene: NEIL1: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 21697813; Phenotypes: SRNS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 MED28 Eleanor Williams reviewed gene: MED28: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 LAMA5 Eleanor Williams reviewed gene: LAMA5: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 29534211; Phenotypes: No OMIM disease association; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 KANK4 Eleanor Williams reviewed gene: KANK4: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 25961457; Phenotypes: No OMIM disease association; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 KANK1 Eleanor Williams reviewed gene: KANK1: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 25961457; Phenotypes: Steroid sensitive resistant nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 E2F3 Eleanor Williams reviewed gene: E2F3: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 21372519; Phenotypes: FSGS + mental retardation (No OMIM ref); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 CYP11B2 Eleanor Williams reviewed gene: CYP11B2: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 9814506, PMID: 24022297; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency #203400, Hypoaldosteronism, congenital, due to CMO II deficiency #610600; Mode of inheritance: Unknown; Current diagnostic: yes
Proteinuric renal disease v1.16 COQ9 Eleanor Williams reviewed gene: COQ9: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 19375058; Phenotypes: Coenzyme Q10 deficiency, primary, 5 #614654; Mode of inheritance: ; Current diagnostic: yes
Proteinuric renal disease v1.16 COQ7 Eleanor Williams reviewed gene: COQ7: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 26084283; Phenotypes: ?Coenzyme Q10 deficiency, primary, 8 #616733; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 COL4A1 Eleanor Williams reviewed gene: COL4A1: Rating: RED; Mode of pathogenicity: ; Publications: PMID27190376; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps #611773; Mode of inheritance: ; Current diagnostic: yes
Proteinuric renal disease v1.16 CDK20 Eleanor Williams reviewed gene: CDK20: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 29773874; Phenotypes: Chronic kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 CD151 Eleanor Williams reviewed gene: CD151: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 15265795; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness #609057; Mode of inheritance: Unknown; Current diagnostic: yes
Proteinuric renal disease v1.16 GIF Eleanor Williams reviewed gene: GIF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 ARHGAP24 Eleanor Williams reviewed gene: ARHGAP24: Rating: RED; Mode of pathogenicity: ; Publications: PMID21911940; Phenotypes: Focal segmental glomerulosclerosis ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 ANKFY1 Eleanor Williams reviewed gene: ANKFY1: Rating: RED; Mode of pathogenicity: ; Publications: PMID: 29959197; Phenotypes: No OMIM disease association; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 ZMPSTE24 Eleanor Williams reviewed gene: ZMPSTE24: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 17152860 ; Phenotypes: Mandibuloacral dysplasia with type B lipodystrophy #608612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 VPS33B Eleanor Williams reviewed gene: VPS33B: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 18853461; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 #208085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 VIPAS39 Eleanor Williams reviewed gene: VIPAS39: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 20190753; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2 # 613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 TTC21B Eleanor Williams reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 26940125, PMID: 24876116 ; Phenotypes: Nephronophthisis 12 # 613820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 TPRKB Eleanor Williams reviewed gene: TPRKB: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 28805828; Phenotypes: Galloway-Mowat syndrome 5 #617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 SYNPO Eleanor Williams reviewed gene: SYNPO: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 19666657; Phenotypes: FSGS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 PTPRO Eleanor Williams reviewed gene: PTPRO: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 21722858, PMID: 30065916 ; Phenotypes: Nephrotic syndrome, type 6 #614196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 PMM2 Eleanor Williams reviewed gene: PMM2: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 19474279, PMID: 29229467 ; Phenotypes: Congenital disorder of glycosylation, type Ia #212065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 NUP205 Eleanor Williams reviewed gene: NUP205: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 26878725; Phenotypes: ?Nephrotic syndrome, type 13 #616893; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 NUP160 Eleanor Williams reviewed gene: NUP160: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 30179222 ; Phenotypes: ?Nephrotic syndrome, type 19 #618178; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 NPHP4 Eleanor Williams reviewed gene: NPHP4: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 17954299, PMID 26346198 ; Phenotypes: Nephronophthisis 4 #606966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 MTRR Eleanor Williams reviewed gene: MTRR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Homocystinuria-megaloblastic anemia, cbl E type #236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 MTR Eleanor Williams reviewed gene: MTR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Homocystinuria-megaloblastic anemia, cblG complementation type #250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 MEFV Eleanor Williams reviewed gene: MEFV: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Familial Mediterranean fever, AR #249100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 MAFB Eleanor Williams reviewed gene: MAFB: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID:29779709, PMID: 22387013; Phenotypes: FSGS with Duane retraction syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 LMNA Eleanor Williams reviewed gene: LMNA: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 24080738, PMID: 28620495; Phenotypes: Partial lipodystrophy and FSGS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 LCAT Eleanor Williams reviewed gene: LCAT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Norum disease #245900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 KANK2 Eleanor Williams reviewed gene: KANK2: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 25961457; Phenotypes: Nephrotic syndrome 16 #617783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 ITSN2 Eleanor Williams reviewed gene: ITSN2: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 29773874; Phenotypes: Early childhood SSNS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 ITGB4 Eleanor Williams reviewed gene: ITGB4: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 11328943; Phenotypes: Epidermolysis bullosa, junctional, with pyloric stenosis #226730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 ITGA3 Eleanor Williams reviewed gene: ITGA3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital #614748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 GAPVD1 Eleanor Williams reviewed gene: GAPVD1: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 29959197; Phenotypes: No OMIM disease association; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 DGKE Eleanor Williams reviewed gene: DGKE: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 23274426, PMID: 23542698; Phenotypes: Nephrotic syndrome, type 7 #615008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 CD2AP Eleanor Williams reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 30612599, PMID: 17713465; Phenotypes: Glomerulosclerosis, focal segmental, 3 #607832; Mode of inheritance: Unknown; Current diagnostic: yes
Proteinuric renal disease v1.16 ARHGDIA Eleanor Williams reviewed gene: ARHGDIA: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 23434736, PMID: 23867502, PMID: 30295827; Phenotypes: Nephrotic syndrome, type 8 #615224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 APOL1 Eleanor Williams reviewed gene: APOL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Focal Segmental Glomerulosclerosis 4, Susceptibility to #612551; Mode of inheritance: Unknown
Proteinuric renal disease v1.16 ANLN Eleanor Williams reviewed gene: ANLN: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID24676636, PMID: 30002222; Phenotypes: Focal segmental glomerulosclerosis 8 #616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 AMN Eleanor Williams reviewed gene: AMN: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 26040326; Phenotypes: Megaloblastic anemia-1, Norwegian type #261100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 ALMS1 Eleanor Williams reviewed gene: ALMS1: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID25846608; Phenotypes: Alstrom Syndrome #203800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 ALG1 Eleanor Williams reviewed gene: ALG1: Rating: AMBER; Mode of pathogenicity: ; Publications: PMID: 27325525; Phenotypes: Congenital disorder of glycosylation, type Ik #608540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 TBC1D8B Eleanor Williams reviewed gene: TBC1D8B: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30661770 ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuric renal disease v1.16 WT1 Eleanor Williams reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Denys-Drash syndrome #194080, Frasier syndrome #136680, Wilms tumor, type 1 #194070; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 WDR73 Eleanor Williams reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26123727, PMID: 25466283 ; Phenotypes: Galloway-Mowat syndrome 1 #251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 TRPC6 Eleanor Williams reviewed gene: TRPC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Glomerulosclerosis, focal segmental, 2 #603652; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 TP53RK Eleanor Williams reviewed gene: TP53RK: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28805828; Phenotypes: Galloway-Mowat syndrome 4 #617730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 TNS2 Eleanor Williams reviewed gene: TNS2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID : 29773874; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v1.16 SMARCAL1 Eleanor Williams reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 11799392; Phenotypes: Schimke immunoosseous dysplasia #242900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 SGPL1 Eleanor Williams reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28181337; Phenotypes: Nephrotic syndrome, type 14 #617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 SCARB2 Eleanor Williams reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: ; Publications: https://doi.org/10.1186/1471-2377-11-134, 22032306; Phenotypes: Epilepsy, progressive myoclonic 4, with or without renal failure #254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 PODXL Eleanor Williams reviewed gene: PODXL: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30523047, PMID: 29244787; Phenotypes: Congenital nephrotic syndrome ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Proteinuric renal disease v1.16 PLCE1 Eleanor Williams reviewed gene: PLCE1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 20591883; Phenotypes: Nephrotic syndrome, type 3 #610725; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 PDSS2 Eleanor Williams reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 23926186 ; Phenotypes: Coenzyme Q10 deficiency, primary, 3 #614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 PAX2 Eleanor Williams reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26571382; Phenotypes: Glomerulosclerosis, focal segmental, 7 #616002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 OSGEP Eleanor Williams reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28805828; Phenotypes: Galloway-Mowat syndrome 3 #617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 OCRL Eleanor Williams reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 21249396 , PMID: 17384968 ; Phenotypes: LOWE OCULOCEREBRORENAL SYNDROME #309000, Dent disease 2 #300555; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.16 NUP93 Eleanor Williams reviewed gene: NUP93: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26878725; Phenotypes: Nephrotic syndrome, type 12 #616892; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 NUP85 Eleanor Williams reviewed gene: NUP85: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30179222; Phenotypes: Nephrotic syndrome, type 17 #618176; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 NUP133 Eleanor Williams reviewed gene: NUP133: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30179222 ; Phenotypes: Nephrotic syndrome, type 18 #618177; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 NUP107 Eleanor Williams reviewed gene: NUP107: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26411495, PMID 30179222 ; Phenotypes: Nephrotic syndrome, type 11 #616730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 NPHS2 Eleanor Williams reviewed gene: NPHS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephrotic syndrome, type 2 #600995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 NPHS1 Eleanor Williams reviewed gene: NPHS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephrotic syndrome, type 1 #602716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 MYO1E Eleanor Williams reviewed gene: MYO1E: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 23595123, PMID:21697813; Phenotypes: Glomerulosclerosis, focal segmental, 6 #614131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 MYH9 Eleanor Williams reviewed gene: MYH9: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 12792306, 22627578; Phenotypes: Epstein syndrome #153650, Fechtner syndrome #153640; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 MAGI2 Eleanor Williams reviewed gene: MAGI2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29773874, PMID: 27932480; Phenotypes: Nephrotic syndrome, type 15 # 617609; Mode of inheritance: ; Current diagnostic: yes
Proteinuric renal disease v1.16 LMX1B Eleanor Williams reviewed gene: LMX1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nail-patella syndrome #161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 LAMB2 Eleanor Williams reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephrotic syndrome, type 5, with or without ocular abnormalities #614199, Pierson syndrome #609049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 LAGE3 Eleanor Williams reviewed gene: LAGE3: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 28805828; Phenotypes: Galloway-Mowat syndrome 2, X-linked #301006; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Proteinuric renal disease v1.16 ITSN1 Eleanor Williams reviewed gene: ITSN1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29773874; Phenotypes: Early childhood SSNS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 INF2 Eleanor Williams reviewed gene: INF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Glomerulosclerosis, focal segmental, 5 #613237; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.16 GLA Eleanor Williams reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Proteinuric renal disease v1.16 FAT1 Eleanor Williams reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26905694; Phenotypes: Glomerulotubular nephropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 EMP2 Eleanor Williams reviewed gene: EMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID24814193; Phenotypes: Nephrotic syndrome, type 10 #615861; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 DLC1 Eleanor Williams reviewed gene: DLC1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29773874; Phenotypes: Childhood and adult SSNS and SRNS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 DHFR Eleanor Williams reviewed gene: DHFR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v1.16 CUBN Eleanor Williams reviewed gene: CUBN: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 22574174, PMID: 21903995; Phenotypes: Megaloblastic anemia-1, Finnish type #261100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 CRB2 Eleanor Williams reviewed gene: CRB2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 25557779, PMID: 29473663; Phenotypes: Focal segmental glomerulosclerosis 9 #616220, Ventriculomegaly with cystic kidney disease #219730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 COQ8B Eleanor Williams reviewed gene: COQ8B: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 24270420; Phenotypes: Nephrotic syndrome, type 9 #615573; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.16 COQ6 Eleanor Williams reviewed gene: COQ6: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID21540551; Phenotypes: Coenzyme Q10 deficiency, primary, 6 #614650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 COQ2 Eleanor Williams reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29637272, PMID: 30180404 ; Phenotypes: Coenzyme Q10 deficiency, primary, 1 #607426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 COL4A5 Eleanor Williams reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29987460, 29270492; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Proteinuric renal disease v1.16 COL4A4 Eleanor Williams reviewed gene: COL4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30506145, 29987460, 24052634 ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 COL4A3 Eleanor Williams reviewed gene: COL4A3: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 30506145, 29987460, 24052634 ; Phenotypes: Alport syndrome, autosomal dominant #104200, Alport syndrome, autosomal recessive #203780, Hematuria, benign familial #141200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.16 CLCN5 Eleanor Williams reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID27757584, PMID: 25907713; Phenotypes: Dent disease #300009, Proteinuria low molecular weight #308990; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Proteinuric renal disease v1.16 ACTN4 Eleanor Williams reviewed gene: ACTN4: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 29043128; Phenotypes: Glomerulosclerosis, focal segmental, 1 #603278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Proteinuric renal disease v1.15 XPO5 Eleanor Williams gene: XPO5 was added
gene: XPO5 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: XPO5 was set to
Proteinuric renal disease v1.15 SLC19A3 Eleanor Williams Source NHS GMS was added to SLC19A3.
Proteinuric renal disease v1.15 SLC19A2 Eleanor Williams Source NHS GMS was added to SLC19A2.
Proteinuric renal disease v1.15 NXF5 Eleanor Williams gene: NXF5 was added
gene: NXF5 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NXF5 was set to
Proteinuric renal disease v1.15 NLRP3 Eleanor Williams gene: NLRP3 was added
gene: NLRP3 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NLRP3 was set to
Proteinuric renal disease v1.15 NEU1 Eleanor Williams gene: NEU1 was added
gene: NEU1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NEU1 was set to
Proteinuric renal disease v1.15 NEIL1 Eleanor Williams gene: NEIL1 was added
gene: NEIL1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NEIL1 was set to
Proteinuric renal disease v1.15 MED28 Eleanor Williams gene: MED28 was added
gene: MED28 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: MED28 was set to
Proteinuric renal disease v1.15 LAMA5 Eleanor Williams gene: LAMA5 was added
gene: LAMA5 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: LAMA5 was set to
Proteinuric renal disease v1.15 KANK4 Eleanor Williams gene: KANK4 was added
gene: KANK4 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: KANK4 was set to
Proteinuric renal disease v1.15 KANK1 Eleanor Williams gene: KANK1 was added
gene: KANK1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: KANK1 was set to
Proteinuric renal disease v1.15 E2F3 Eleanor Williams Source NHS GMS was added to E2F3.
Proteinuric renal disease v1.15 CYP11B2 Eleanor Williams Source NHS GMS was added to CYP11B2.
Proteinuric renal disease v1.15 COQ9 Eleanor Williams gene: COQ9 was added
gene: COQ9 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: COQ9 was set to
Proteinuric renal disease v1.15 COQ7 Eleanor Williams gene: COQ7 was added
gene: COQ7 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: COQ7 was set to
Proteinuric renal disease v1.15 COL4A1 Eleanor Williams gene: COL4A1 was added
gene: COL4A1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: COL4A1 was set to
Proteinuric renal disease v1.15 CDK20 Eleanor Williams gene: CDK20 was added
gene: CDK20 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: CDK20 was set to
Proteinuric renal disease v1.15 CD151 Eleanor Williams Source NHS GMS was added to CD151.
Proteinuric renal disease v1.15 GIF Eleanor Williams Source NHS GMS was added to GIF.
Proteinuric renal disease v1.15 ARHGAP24 Eleanor Williams Source NHS GMS was added to ARHGAP24.
Proteinuric renal disease v1.15 ANKFY1 Eleanor Williams gene: ANKFY1 was added
gene: ANKFY1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: ANKFY1 was set to
Proteinuric renal disease v1.15 ZMPSTE24 Eleanor Williams Source NHS GMS was added to ZMPSTE24.
Proteinuric renal disease v1.15 VPS33B Eleanor Williams gene: VPS33B was added
gene: VPS33B was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: VPS33B was set to
Proteinuric renal disease v1.15 VIPAS39 Eleanor Williams gene: VIPAS39 was added
gene: VIPAS39 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: VIPAS39 was set to
Proteinuric renal disease v1.15 TTC21B Eleanor Williams gene: TTC21B was added
gene: TTC21B was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: TTC21B was set to
Proteinuric renal disease v1.15 TPRKB Eleanor Williams gene: TPRKB was added
gene: TPRKB was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: TPRKB was set to
Proteinuric renal disease v1.15 SYNPO Eleanor Williams gene: SYNPO was added
gene: SYNPO was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: SYNPO was set to
Proteinuric renal disease v1.15 PTPRO Eleanor Williams Source NHS GMS was added to PTPRO.
Proteinuric renal disease v1.15 PMM2 Eleanor Williams Source NHS GMS was added to PMM2.
Proteinuric renal disease v1.15 NUP205 Eleanor Williams gene: NUP205 was added
gene: NUP205 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NUP205 was set to
Proteinuric renal disease v1.15 NUP160 Eleanor Williams gene: NUP160 was added
gene: NUP160 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NUP160 was set to
Proteinuric renal disease v1.15 NPHP4 Eleanor Williams gene: NPHP4 was added
gene: NPHP4 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NPHP4 was set to
Proteinuric renal disease v1.15 MTRR Eleanor Williams Source NHS GMS was added to MTRR.
Proteinuric renal disease v1.15 MTR Eleanor Williams Source NHS GMS was added to MTR.
Proteinuric renal disease v1.15 MEFV Eleanor Williams gene: MEFV was added
gene: MEFV was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: MEFV was set to
Proteinuric renal disease v1.15 MAFB Eleanor Williams gene: MAFB was added
gene: MAFB was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: MAFB was set to
Proteinuric renal disease v1.15 LMNA Eleanor Williams gene: LMNA was added
gene: LMNA was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: LMNA was set to
Proteinuric renal disease v1.15 LCAT Eleanor Williams Source NHS GMS was added to LCAT.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 KANK2 Eleanor Williams Source NHS GMS was added to KANK2.
Proteinuric renal disease v1.15 ITSN2 Eleanor Williams gene: ITSN2 was added
gene: ITSN2 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: ITSN2 was set to
Proteinuric renal disease v1.15 ITGB4 Eleanor Williams Source NHS GMS was added to ITGB4.
Proteinuric renal disease v1.15 ITGA3 Eleanor Williams Source NHS GMS was added to ITGA3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 GAPVD1 Eleanor Williams gene: GAPVD1 was added
gene: GAPVD1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: GAPVD1 was set to
Proteinuric renal disease v1.15 DGKE Eleanor Williams gene: DGKE was added
gene: DGKE was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: DGKE was set to
Proteinuric renal disease v1.15 CD2AP Eleanor Williams Source NHS GMS was added to CD2AP.
Proteinuric renal disease v1.15 ARHGDIA Eleanor Williams Source NHS GMS was added to ARHGDIA.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 APOL1 Eleanor Williams Source NHS GMS was added to APOL1.
Proteinuric renal disease v1.15 ANLN Eleanor Williams Source NHS GMS was added to ANLN.
Proteinuric renal disease v1.15 AMN Eleanor Williams Source NHS GMS was added to AMN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 ALMS1 Eleanor Williams Source NHS GMS was added to ALMS1.
Proteinuric renal disease v1.15 ALG1 Eleanor Williams Source NHS GMS was added to ALG1.
Proteinuric renal disease v1.15 TBC1D8B Eleanor Williams gene: TBC1D8B was added
gene: TBC1D8B was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: TBC1D8B was set to
Proteinuric renal disease v1.15 WT1 Eleanor Williams Source NHS GMS was added to WT1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 WDR73 Eleanor Williams gene: WDR73 was added
gene: WDR73 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: WDR73 was set to
Proteinuric renal disease v1.15 TRPC6 Eleanor Williams Source NHS GMS was added to TRPC6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 TP53RK Eleanor Williams gene: TP53RK was added
gene: TP53RK was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: TP53RK was set to
Proteinuric renal disease v1.15 TNS2 Eleanor Williams gene: TNS2 was added
gene: TNS2 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: TNS2 was set to
Proteinuric renal disease v1.15 SMARCAL1 Eleanor Williams Source NHS GMS was added to SMARCAL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 SGPL1 Eleanor Williams Source NHS GMS was added to SGPL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 SCARB2 Eleanor Williams Source NHS GMS was added to SCARB2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 PODXL Eleanor Williams gene: PODXL was added
gene: PODXL was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: PODXL was set to
Proteinuric renal disease v1.15 PLCE1 Eleanor Williams Source NHS GMS was added to PLCE1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 PDSS2 Eleanor Williams Source NHS GMS was added to PDSS2.
Proteinuric renal disease v1.15 PAX2 Eleanor Williams gene: PAX2 was added
gene: PAX2 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: PAX2 was set to
Proteinuric renal disease v1.15 OSGEP Eleanor Williams Source NHS GMS was added to OSGEP.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 OCRL Eleanor Williams gene: OCRL was added
gene: OCRL was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: OCRL was set to
Proteinuric renal disease v1.15 NUP93 Eleanor Williams Source NHS GMS was added to NUP93.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 NUP85 Eleanor Williams gene: NUP85 was added
gene: NUP85 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NUP85 was set to
Proteinuric renal disease v1.15 NUP133 Eleanor Williams gene: NUP133 was added
gene: NUP133 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NUP133 was set to
Proteinuric renal disease v1.15 NUP107 Eleanor Williams gene: NUP107 was added
gene: NUP107 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: NUP107 was set to
Proteinuric renal disease v1.15 NPHS2 Eleanor Williams Source NHS GMS was added to NPHS2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 NPHS1 Eleanor Williams Source NHS GMS was added to NPHS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 MYO1E Eleanor Williams Source NHS GMS was added to MYO1E.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 MYH9 Eleanor Williams Source NHS GMS was added to MYH9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 MAGI2 Eleanor Williams gene: MAGI2 was added
gene: MAGI2 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: MAGI2 was set to
Proteinuric renal disease v1.15 LMX1B Eleanor Williams Source NHS GMS was added to LMX1B.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 LAMB2 Eleanor Williams Source NHS GMS was added to LAMB2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 LAGE3 Eleanor Williams gene: LAGE3 was added
gene: LAGE3 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: LAGE3 was set to
Proteinuric renal disease v1.15 ITSN1 Eleanor Williams gene: ITSN1 was added
gene: ITSN1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: ITSN1 was set to
Proteinuric renal disease v1.15 INF2 Eleanor Williams Source NHS GMS was added to INF2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 GLA Eleanor Williams gene: GLA was added
gene: GLA was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: GLA was set to
Proteinuric renal disease v1.15 FAT1 Eleanor Williams gene: FAT1 was added
gene: FAT1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: FAT1 was set to
Proteinuric renal disease v1.15 EMP2 Eleanor Williams Source NHS GMS was added to EMP2.
Rating Changed from No List (delete) to Red List (low evidence)
Proteinuric renal disease v1.15 DLC1 Eleanor Williams gene: DLC1 was added
gene: DLC1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: DLC1 was set to
Proteinuric renal disease v1.15 DHFR Eleanor Williams Source NHS GMS was added to DHFR.
Proteinuric renal disease v1.15 CUBN Eleanor Williams Source NHS GMS was added to CUBN.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 CRB2 Eleanor Williams Source NHS GMS was added to CRB2.
Rating Changed from No List (delete) to Red List (low evidence)
Proteinuric renal disease v1.15 COQ8B Eleanor Williams gene: COQ8B was added
gene: COQ8B was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: COQ8B was set to
Proteinuric renal disease v1.15 COQ6 Eleanor Williams Source NHS GMS was added to COQ6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 COQ2 Eleanor Williams Source NHS GMS was added to COQ2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 COL4A5 Eleanor Williams Source NHS GMS was added to COL4A5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 COL4A4 Eleanor Williams Source NHS GMS was added to COL4A4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 COL4A3 Eleanor Williams Source NHS GMS was added to COL4A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 CLCN5 Eleanor Williams Source NHS GMS was added to CLCN5.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.15 ACTN4 Eleanor Williams Source NHS GMS was added to ACTN4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Proteinuric renal disease v1.14 MTR Eleanor Williams Phenotypes for gene: MTR were changed from Homocystinuria-megaloblastic anemia, cblG complementation type, 250940{Neural tube defects, folate-sensitive, susceptibility to}, 601634; (originally on the Imerslund-Grasbeck syndrome gene panel) to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; {Neural tube defects, folate-sensitive, susceptibility to}, 601634; (originally on the Imerslund-Grasbeck syndrome gene panel)
Proteinuric renal disease v1.12 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Proteinuric renal disease v1.11 GIF Louise Daugherty Tag new-gene-name tag was added to gene: GIF.
Proteinuric renal disease v1.11 GIF Louise Daugherty commented on gene: GIF
Proteinuric renal disease v1.11 CRB2 John Sayer gene: CRB2 was added
gene: CRB2 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: CRB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRB2 were set to 25557779; 27942854
Phenotypes for gene: CRB2 were set to steroid resistant nephrotic syndrome
Penetrance for gene: CRB2 were set to Complete
Review for gene: CRB2 was set to GREEN
Added comment: Sources: Literature
Proteinuric renal disease v1.11 EMP2 John Sayer gene: EMP2 was added
gene: EMP2 was added to Proteinuric renal disease. Sources: Literature
Mode of inheritance for gene: EMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMP2 were set to 24814193
Phenotypes for gene: EMP2 were set to steroid sensitive nephrotic syndrome
Penetrance for gene: EMP2 were set to Complete
Review for gene: EMP2 was set to GREEN
Added comment: Sources: Literature
Proteinuric renal disease OSGEP Helen Brittain marked gene: OSGEP as ready
Proteinuric renal disease OSGEP Helen Brittain classified OSGEP as Green List (high evidence)
Proteinuric renal disease OSGEP Helen Brittain Added gene to panel
Proteinuric renal disease SGPL1 Sarah Leigh classified SGPL1 as green
Proteinuric renal disease SGPL1 Sarah Leigh added SGPL1 to panel
Proteinuric renal disease SGPL1 Sarah Leigh reviewed SGPL1
Proteinuric renal disease ANLN Sarah Leigh classified ANLN as amber
Proteinuric renal disease ANLN Sarah Leigh added ANLN to panel
Proteinuric renal disease ANLN Sarah Leigh reviewed ANLN
Proteinuric renal disease LCAT Sarah Leigh classified LCAT as green
Proteinuric renal disease LCAT Sarah Leigh added LCAT to panel
Proteinuric renal disease LCAT Sarah Leigh reviewed LCAT