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Renal tubulopathies v4.17 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Renal tubulopathies v4.15 SLC12A3 Sarah Leigh Phenotypes for gene: SLC12A3 were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Gitelman syndrome, 263800 to Gitelman syndrome, OMIM: 263800; Gitelman syndrome, MONDO:0009904
Renal tubulopathies v4.14 SLC12A3 Sarah Leigh Tag monogenic-polygenic was removed from gene: SLC12A3.
Tag monogenic - polygenic tag was added to gene: SLC12A3.
Renal tubulopathies v4.14 SLC12A3 Sarah Leigh Publications for gene: SLC12A3 were set to
Renal tubulopathies v4.13 SLC12A3 Sarah Leigh Tag monogenic-polygenic tag was added to gene: SLC12A3.
Renal tubulopathies v4.13 SLC12A3 Sarah Leigh commented on gene: SLC12A3
Renal tubulopathies v4.13 SLC12A1 Sarah Leigh commented on gene: SLC12A1
Renal tubulopathies v4.13 SLC12A1 Sarah Leigh Publications for gene: SLC12A1 were set to 8640224; 30999883; 32506365; 26770037; 27103762; 8640224; 9355073; 28095294; 32506365
Renal tubulopathies v4.12 SLC12A1 Sarah Leigh Tag monogenic-polygenic tag was added to gene: SLC12A1.
Renal tubulopathies v4.12 SLC12A1 Sarah Leigh Phenotypes for gene: SLC12A1 were changed from Type 1 Bartter syndrome: infantile onset, pregnancy noted for polyhydramnios. Hyperprostagladinuria. Hypokalaemia and metabolic alkalosis +/- nephrocalcinosis; Bartter syndrome, type 1, 601678 to Bartter syndrome, type 1, OMIM:601678; Bartter disease type 1, MONDO:0100344
Renal tubulopathies v4.11 SLC12A1 Sarah Leigh Publications for gene: SLC12A1 were set to 8640224; 30999883; 32506365; 26770037; 27103762
Renal tubulopathies v4.10 CLCNKA Sarah Leigh Classified gene: CLCNKA as Red List (low evidence)
Renal tubulopathies v4.10 CLCNKA Sarah Leigh Gene: clcnka has been classified as Red List (Low Evidence).
Renal tubulopathies v4.9 CLCNKA Sarah Leigh Classified gene: CLCNKA as Red List (low evidence)
Renal tubulopathies v4.9 CLCNKA Sarah Leigh Added comment: Comment on list classification: The rating of this gene is being changed to Red from Amber, to reflect that GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Renal tubulopathies v4.9 CLCNKA Sarah Leigh Gene: clcnka has been classified as Red List (Low Evidence).
Renal tubulopathies v4.8 CLCNKA Sarah Leigh Phenotypes for gene: CLCNKA were changed from Bartter syndrome, type 4b, digenic, OMIM:613090 to Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Renal tubulopathies v4.7 CLCNKA Sarah Leigh Added comment: Comment on mode of inheritance: Digenic CLCNKA & CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090)(PMID: 15044642;18310267;32488762). The current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Renal tubulopathies v4.7 CLCNKA Sarah Leigh Mode of inheritance for gene: CLCNKA was changed from BIALLELIC, autosomal or pseudoautosomal to Other
Renal tubulopathies v4.6 CLCNKA Sarah Leigh Tag polygenic tag was added to gene: CLCNKA.
Renal tubulopathies v4.6 CLCNKA Sarah Leigh Publications for gene: CLCNKA were set to 18310267; 32488762
Renal tubulopathies v4.5 CLCNKB Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for CLCNKB should be BIALLELIC, autosomal or pseudoautosomal. Although digenic CLCNKB & CLCNKA variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090), the current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Renal tubulopathies v4.5 CLCNKB Sarah Leigh Mode of inheritance for gene: CLCNKB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v4.4 CLCNKB Sarah Leigh Tag monogenic-polygenic tag was added to gene: CLCNKB.
Renal tubulopathies v4.4 CLCNKB Sarah Leigh Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 3, OMIM:607364; Bartter syndrome, type 4b, digenic, OMIM:613090 to Bartter syndrome, type 3, OMIM:607364; Bartter disease type 3, MONDO:0011822; Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Renal tubulopathies v4.3 CLCNKB Sarah Leigh Deleted their comment
Renal tubulopathies v4.3 RMND1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: RMND1.
Tag Q3_23_NHS_review tag was added to gene: RMND1.
Renal tubulopathies v4.3 RMND1 Achchuthan Shanmugasundram Classified gene: RMND1 as Amber List (moderate evidence)
Renal tubulopathies v4.3 RMND1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next GMS review.
Renal tubulopathies v4.3 RMND1 Achchuthan Shanmugasundram Gene: rmnd1 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v4.2 RMND1 Achchuthan Shanmugasundram Phenotypes for gene: RMND1 were changed from tubulopathy; renal tubular acidosis; interstitial nephritis; end-stage renal disease; tubular atrophy to Combined oxidative phosphorylation deficiency 11, OMIM:614922; tubulopathy; renal tubular acidosis; interstitial nephritis; end-stage renal disease; tubular atrophy
Renal tubulopathies v4.1 RMND1 Achchuthan Shanmugasundram changed review comment from: PMID:31568715 - Four patients identified with pathogenic variants in RMND1 were reported with renal disease characterised by tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4).

PMID:31889854 - A very rare homozygous pathogenic variant in RMND1 (p.Val211Met) was identified in a patient presenting with chronic kidney disease (CKD) and sensorineural hearing loss (SNHL).

PMID:32911714 - Compound heterozygous missense variants in RMND1 (p.Gly195Arg & p.Tyr273Ser) was identified in female siblings presenting with severe-to-profound bilateral SNHL, ovarian dysfunction and CKD that developed in the fourth decade of life.; to: PMID:31568715 - Four patients identified with pathogenic variants in RMND1 were reported with renal disease characterised by tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4).

PMID:31889854 - A very rare homozygous pathogenic variant in RMND1 (p.Val211Met) was identified in a patient presenting with chronic kidney disease (CKD) and sensorineural hearing loss (SNHL).

PMID:32911714 - Compound heterozygous missense variants in RMND1 (p.Gly195Arg & p.Tyr273Ser) was identified in female siblings presenting with severe-to-profound bilateral SNHL, ovarian dysfunction and CKD that developed in the fourth decade of life.

This gene has been associated with relevant phenotypes in both OMIM (MIM #614922) and Gene2Phenotype. The clinical manifestations such as cystic kidneys, renal tubular acidosis and renal disease have been recorded as part of the OMIM phenotype.
Renal tubulopathies v4.1 RMND1 Achchuthan Shanmugasundram reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31568715, 31889854, 32911714; Phenotypes: Combined oxidative phosphorylation deficiency 11, OMIM:614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v4.1 RMND1 John Sayer gene: RMND1 was added
gene: RMND1 was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RMND1 were set to 32911714; 31889854; 31568715
Phenotypes for gene: RMND1 were set to tubulopathy; renal tubular acidosis; interstitial nephritis; end-stage renal disease; tubular atrophy
Penetrance for gene: RMND1 were set to Complete
Mode of pathogenicity for gene: RMND1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RMND1 was set to GREEN
Added comment: Sources: Expert list
Renal tubulopathies v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Renal tubulopathies v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Renal tubulopathies v3.6 WDR72 Eleanor Williams Publications for gene: WDR72 were set to 30028003
Renal tubulopathies v3.5 WDR72 Eleanor Williams Phenotypes for gene: WDR72 were changed from distal RTA; hereditary distal renal tubular acidosis to distal RTA; hereditary distal renal tubular acidosis; distal renal tubular acidosis, MONDO:0015827; Amelogenesis imperfecta, type IIA3, OMIM:613211; amelogenesis imperfecta hypomaturation type 2A3, MONDO:0013181
Renal tubulopathies v3.4 WDR72 Eleanor Williams Tag Q1_23_promote_green tag was added to gene: WDR72.
Renal tubulopathies v3.4 WDR72 Eleanor Williams commented on gene: WDR72: Additional families reported with distal renal tubular acidosis, along with amelogenesis imperfecta.

PMID: 30779877 (Zhang et al 2019) - 6 families (1 African, 5 Turkish) identified using WES with biallelic WDR72 variants. The affected members showed generalized hypomaturation Amelogenesis imperfecta. 2 families, although unrelated, shared the same variant. 3 out of the 8 tested patients showed decreased serum pH, consistent with a diagnosis of renal tubular acidosis.

PMID: 31959358 - (Jobst-Schwan et al 2020) - 2 families (Indian, Turkish) with different homozygous variants in WDR72 identified by WES. All 3 affected individuals had Distal renal tubular acidosis. 1 individual is reported to have nephrocalcinosis.

PMID: 33033857 - Khandelwal et al 2021 - 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Genome analysis of 3 of the patients identified 3 different homozygous nonsense variants in WDR72. Ultrasound showed bilateral grade I medullary nephrocalcinosis in the 3 patients.
Renal tubulopathies v3.4 WDR72 Eleanor Williams changed review comment from: No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype.

PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691).

Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA.; to: No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype.

PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691).

Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA. She also showed nephrocalcinosis.
Renal tubulopathies v3.4 CTNS Achchuthan Shanmugasundram Publications for gene: CTNS were set to 27604308; 9537412; 19863563
Renal tubulopathies v3.3 SLC9A3R1 Eleanor Williams Tag new-gene-name tag was added to gene: SLC9A3R1.
Renal tubulopathies v3.3 SLC9A3R1 Eleanor Williams commented on gene: SLC9A3R1: Added new-gene-name tag, new approved HGNC gene symbol for SLC9A3R1 (HGNC:11075) is NHERF1.
Renal tubulopathies v3.3 SEC61A1 Sarah Leigh Tag Q2_22_rating was removed from gene: SEC61A1.
Tag Q2_22_phenotype was removed from gene: SEC61A1.
Tag Q2_22_expert_review was removed from gene: SEC61A1.
Renal tubulopathies v3.3 RRAGD Sarah Leigh Tag Q3_22_rating was removed from gene: RRAGD.
Tag Q3_22_NHS_review was removed from gene: RRAGD.
Renal tubulopathies v3.3 KCNJ16 Sarah Leigh Tag Q2_22_rating was removed from gene: KCNJ16.
Renal tubulopathies v3.3 CNNM2 Sarah Leigh Tag Q3_22_rating was removed from gene: CNNM2.
Tag Q3_22_MOI was removed from gene: CNNM2.
Tag Q3_22_NHS_review was removed from gene: CNNM2.
Renal tubulopathies v3.3 SEC61A1 Sarah Leigh reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 RRAGD Sarah Leigh reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 KCNJ16 Sarah Leigh reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 CNNM2 Sarah Leigh reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.2 SEC61A1 Sarah Leigh Source Expert Review Green was added to SEC61A1.
Source NHS GMS was added to SEC61A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 RRAGD Sarah Leigh Source Expert Review Green was added to RRAGD.
Source NHS GMS was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 KCNJ16 Sarah Leigh Source Expert Review Green was added to KCNJ16.
Source NHS GMS was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 CNNM2 Sarah Leigh Source Expert Review Green was added to CNNM2.
Source NHS GMS was added to CNNM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Renal tubulopathies v3.0 Arina Puzriakova promoted panel to version 3.0
Renal tubulopathies v2.63 GATM Arina Puzriakova Phenotypes for gene: GATM were changed from Renal fanconi syndrome and kidney failure (no MIM number); Cerebral creatine deficiency syndrome 3, 612718 (AR) to Fanconi renotubular syndrome 1, OMIM:134600
Renal tubulopathies v2.62 RRAGD Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

As reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. Abstract only accessed.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

As reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. The age of onset was 6 months to 24 years.
Renal tubulopathies v2.62 RRAGD Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype.

As reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members.; to: Not associated with a phenotype in OMIM or Gene2Phenotype.

As reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. Abstract only accessed.
Renal tubulopathies v2.62 RRAGD Eleanor Williams Classified gene: RRAGD as Amber List (moderate evidence)
Renal tubulopathies v2.62 RRAGD Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with a recommendation for GREEN rating following GMS review.
Renal tubulopathies v2.62 RRAGD Eleanor Williams Gene: rragd has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.61 RRAGD Eleanor Williams commented on gene: RRAGD
Renal tubulopathies v2.61 RRAGD Eleanor Williams Phenotypes for gene: RRAGD were changed from hypomagnesaemia; cardiomyopathy to hypomagnesaemia; cardiomyopathy; tubular renal disease-cardiomyopathy syndrome, MONDO:0019130
Renal tubulopathies v2.60 RRAGD Eleanor Williams Publications for gene: RRAGD were set to PMID: 34607910
Renal tubulopathies v2.59 RRAGD Eleanor Williams Tag Q3_22_rating tag was added to gene: RRAGD.
Tag Q3_22_NHS_review tag was added to gene: RRAGD.
Renal tubulopathies v2.59 CNNM2 Eleanor Williams Classified gene: CNNM2 as Amber List (moderate evidence)
Renal tubulopathies v2.59 CNNM2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber but with a recommendation of GREEN rating following GMS review. Many monoallelic cases reported plus 2 biallelic.
Renal tubulopathies v2.59 CNNM2 Eleanor Williams Gene: cnnm2 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.58 CNNM2 Eleanor Williams Tag Q3_22_rating tag was added to gene: CNNM2.
Tag Q3_22_MOI tag was added to gene: CNNM2.
Tag Q3_22_NHS_review tag was added to gene: CNNM2.
Renal tubulopathies v2.58 CNNM2 Eleanor Williams Phenotypes for gene: CNNM2 were changed from hypomagnesaemia; seizures; intellectual disability to Hypomagnesemia 6, renal, OMIM:613882; Hypomagnesemia, seizures, and mental retardation, OMIM:616418; renal hypomagnesemia 6, MONDO:0013480; Hypomagnesemia, seizures, and mental retardation, MONDO:0014631
Renal tubulopathies v2.57 CNNM2 Eleanor Williams Publications for gene: CNNM2 were set to PMID: 33600043; 30026055; 32997713; 34604137; 33859252; 24699222; 35002148; 21397062
Renal tubulopathies v2.56 CNNM2 Eleanor Williams Added comment: Comment on mode of pathogenicity: There is a mix of missense and truncating variants reported.
Renal tubulopathies v2.56 CNNM2 Eleanor Williams Mode of pathogenicity for gene: CNNM2 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Other
Renal tubulopathies v2.55 CNNM2 Eleanor Williams Mode of inheritance for gene: CNNM2 was changed from Other to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal tubulopathies v2.54 CNNM2 Eleanor Williams reviewed gene: CNNM2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomagnesemia 6, renal, OMIM:613882, Hypomagnesemia, seizures, and mental retardation, OMIM:616418, renal hypomagnesemia 6, MONDO:0013480; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Renal tubulopathies v2.54 RRAGD Detlef Bockenhauer gene: RRAGD was added
gene: RRAGD was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: RRAGD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGD were set to PMID: 34607910
Phenotypes for gene: RRAGD were set to hypomagnesaemia; cardiomyopathy
Penetrance for gene: RRAGD were set to Complete
Mode of pathogenicity for gene: RRAGD was set to Other
Review for gene: RRAGD was set to GREEN
Added comment: publication from Nov 2021, reporting on 8 unrelated children with a phenotype of hypokalaemia, hypomagnesaemia and dilative cardiomyopathy who had mostly de novo heterozygous variants in RRAGD. Also identified a family where hypomagnesaemia segregated with a heterozygous variant in RRAGD in 8 members.
In vitro studies of variants are consistent with a gain-of-function, i.e. mTOR activation
Sources: Literature
Renal tubulopathies v2.54 CNNM2 Detlef Bockenhauer gene: CNNM2 was added
gene: CNNM2 was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: CNNM2 was set to Other
Publications for gene: CNNM2 were set to PMID: 33600043; 30026055; 32997713; 34604137; 33859252; 24699222; 35002148; 21397062
Phenotypes for gene: CNNM2 were set to hypomagnesaemia; seizures; intellectual disability
Penetrance for gene: CNNM2 were set to Complete
Mode of pathogenicity for gene: CNNM2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CNNM2 was set to GREEN
Added comment: described with dominant and recessive inheritance (associated with phenotype severity), but mostly with heterozygous de novo variants
Sources: Expert list
Renal tubulopathies v2.54 KCNJ16 Eleanor Williams changed review comment from: Associated with Hypokalemic tubulopathy and deafness OMIM#619406 (AR)

PMID:33811157 - Schlingmann et al 2021 - unable to access publication. Abstract does not give numbers of cases but OMIM states that "In 8 patients, including 1 sib pair, with hypokalemic tubulopathy and deafness, Schlingmann et al. (2021) identified homozygous or compound heterozygous mutations in the KCNJ16 gene"

PMID:33840812 - Webb et al 2021 - report a homozygous loss-of-function variant identified by WES in KCNJ16 in a 2-year-old female with a hypokalemic metabolic acidosis phenotype.; to: Associated with Hypokalemic tubulopathy and deafness OMIM#619406 (AR)

PMID:33811157 - Schlingmann et al 2021 - report 8 patients from 7 families with hypokalemic tubulopathy and deafness. All patients had acidosis and sensorineural deafness. All were found to have homozygous or compound heterozygous variants in the KCNJ16 gene. 6 different variants were identified, either missense or nonsesnse.

PMID:33840812 - Webb et al 2021 - report a homozygous loss-of-function variant identified by WES in KCNJ16 c.142A>T; p.(Lys48*) in a 2-year-old female with a hypokalemic metabolic acidosis phenotype. No loss of hearing was noted.
Renal tubulopathies v2.54 SEC61A1 Eleanor Williams Tag Q2_21_phenotype was removed from gene: SEC61A1.
Tag Q2_21_expert_review was removed from gene: SEC61A1.
Tag Q2_22_phenotype tag was added to gene: SEC61A1.
Tag Q2_22_expert_review tag was added to gene: SEC61A1.
Renal tubulopathies v2.54 SEC61A1 Eleanor Williams Tag Q2_21_phenotype tag was added to gene: SEC61A1.
Renal tubulopathies v2.54 SEC61A1 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. This gene should be reviewed to whether the phenotype is appropriate to this panel. There are sufficient cases with Autosomal dominant tubulointerstitial kidney to rate green.; to: Comment on list classification: Promoting from grey to amber. This gene should be reviewed to whether the associated disease phenotype fulfils the eligibility criteria for this panel. There are sufficient cases with Autosomal dominant tubulointerstitial kidney to rate green.
Renal tubulopathies v2.54 KCNJ16 Eleanor Williams Classified gene: KCNJ16 as Amber List (moderate evidence)
Renal tubulopathies v2.54 KCNJ16 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber with a recommendation of green rating following GMS review.
Renal tubulopathies v2.54 KCNJ16 Eleanor Williams Gene: kcnj16 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.53 KCNJ16 Eleanor Williams Tag Q2_22_rating tag was added to gene: KCNJ16.
Renal tubulopathies v2.53 KCNJ16 Eleanor Williams Phenotypes for gene: KCNJ16 were changed from Renal tubulopathy; deafness to Hypokalemic tubulopathy and deafness, OMIM:619406
Renal tubulopathies v2.52 KCNJ16 Eleanor Williams commented on gene: KCNJ16
Renal tubulopathies v2.52 SEC61A1 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. This gene should be reviewed to whether the phenotype is appropriate to this panel; to: Comment on list classification: Promoting from grey to amber. This gene should be reviewed to whether the phenotype is appropriate to this panel. There are sufficient cases with Autosomal dominant tubulointerstitial kidney to rate green.
Renal tubulopathies v2.52 SEC61A1 Eleanor Williams Classified gene: SEC61A1 as Amber List (moderate evidence)
Renal tubulopathies v2.52 SEC61A1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. This gene should be reviewed to whether the phenotype is appropriate to this panel
Renal tubulopathies v2.52 SEC61A1 Eleanor Williams Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.51 SEC61A1 Eleanor Williams Publications for gene: SEC61A1 were set to PMID: 33185949; 27392076; 31488840
Renal tubulopathies v2.50 SEC61A1 Eleanor Williams Tag Q2_21_expert_review tag was added to gene: SEC61A1.
Tag Q2_22_rating tag was added to gene: SEC61A1.
Renal tubulopathies v2.50 SEC61A1 Eleanor Williams reviewed gene: SEC61A1: Rating: ; Mode of pathogenicity: None; Publications: 33185949, 30586318, 27392076, 31488840; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal tubulopathies v2.50 KCNJ16 Julia Baptista reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811157, 33840812; Phenotypes: Renal tubulopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v2.50 CLCNKA Sarah Leigh Phenotypes for gene: CLCNKA were changed from Bartter syndrome, type 4b, digenic 613090 to Bartter syndrome, type 4b, digenic, OMIM:613090
Renal tubulopathies v2.49 CLCNKA Sarah Leigh Publications for gene: CLCNKA were set to 18310267
Renal tubulopathies v2.48 CLCNKB Sarah Leigh Publications for gene: CLCNKB were set to 9326936; 18310267; 32506365; 32488762; 30999883
Renal tubulopathies v2.47 SLC12A1 Sarah Leigh Publications for gene: SLC12A1 were set to 8640224; 32506365
Renal tubulopathies v2.46 SLC12A1 Sarah Leigh Publications for gene: SLC12A1 were set to 8640224
Renal tubulopathies v2.45 CLCNKB Sarah Leigh Publications for gene: CLCNKB were set to 9326936; 18310267
Renal tubulopathies v2.44 CLCNKB Sarah Leigh Added comment: Comment on phenotypes: Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria
Renal tubulopathies v2.44 CLCNKB Sarah Leigh Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 3, OMIM:607364; Bartter syndrome, type 4b, digenic, OMIM:613090 to Bartter syndrome, type 3, OMIM:607364; Bartter syndrome, type 4b, digenic, OMIM:613090
Renal tubulopathies v2.43 CLCNKB Sarah Leigh Publications for gene: CLCNKB were set to 9326936; 18310267
Renal tubulopathies v2.42 CLCNKB Sarah Leigh Added comment: Comment on phenotypes: Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria
Renal tubulopathies v2.42 CLCNKB Sarah Leigh Phenotypes for gene: CLCNKB were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Bartter syndrome, type 3, 607394 to Bartter syndrome, type 3, OMIM:607364; Bartter syndrome, type 4b, digenic, OMIM:613090
Renal tubulopathies v2.41 CLCNKB Sarah Leigh Publications for gene: CLCNKB were set to 9326936
Renal tubulopathies v2.40 WNK1 Arina Puzriakova Phenotypes for gene: WNK1 were changed from Pseudohypoaldosteronism, type IIC, 614492 to Pseudohypoaldosteronism, type IIC, OMIM:614492
Renal tubulopathies v2.39 VPS33B Eleanor Williams Phenotypes for gene: VPS33B were changed from Arthrogryposis, renal dysfunction, and cholestasis 1 #208085 to Arthrogryposis, renal dysfunction, and cholestasis 1, OMIM:208085
Renal tubulopathies v2.38 VPS33B Eleanor Williams Tag for-review was removed from gene: VPS33B.
Renal tubulopathies v2.38 VIPAS39 Eleanor Williams Phenotypes for gene: VIPAS39 were changed from Arthrogryposis, renal dysfunction, and cholestasis 2 #613404 to Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404
Renal tubulopathies v2.37 VIPAS39 Eleanor Williams Tag for-review was removed from gene: VIPAS39.
Renal tubulopathies v2.37 SLC2A2 Eleanor Williams Phenotypes for gene: SLC2A2 were changed from Fanconi-Bickel syndrome, MIM# 227810 to Fanconi-Bickel syndrome, OMIM:227810
Renal tubulopathies v2.36 SLC2A2 Eleanor Williams Tag for-review was removed from gene: SLC2A2.
Renal tubulopathies v2.36 SARS2 Eleanor Williams Phenotypes for gene: SARS2 were changed from Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845; Progressive Spastic Paresis to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, OMIM:613845; Progressive Spastic Paresis
Renal tubulopathies v2.35 SARS2 Eleanor Williams Tag for-review was removed from gene: SARS2.
Renal tubulopathies v2.35 HNF4A Eleanor Williams Phenotypes for gene: HNF4A were changed from Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM#616026 to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, OMIM:616026
Renal tubulopathies v2.34 HNF4A Eleanor Williams Tag for-review was removed from gene: HNF4A.
Renal tubulopathies v2.34 CLDN10 Eleanor Williams Phenotypes for gene: CLDN10 were changed from Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number); HELIX syndrome, OMIM:617671 to Hypokalemic-alkalotic salt-losing tubulopathy; HELIX syndrome, OMIM:617671
Renal tubulopathies v2.33 CLDN10 Eleanor Williams Phenotypes for gene: CLDN10 were changed from Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number); HELIX syndrome, 617671 to Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number); HELIX syndrome, OMIM:617671
Renal tubulopathies v2.32 CLDN10 Eleanor Williams Tag for-review was removed from gene: CLDN10.
Renal tubulopathies v2.32 VPS33B Eleanor Williams commented on gene: VPS33B: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Renal tubulopathies v2.32 VIPAS39 Eleanor Williams commented on gene: VIPAS39: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Renal tubulopathies v2.32 SLC2A2 Eleanor Williams commented on gene: SLC2A2
Renal tubulopathies v2.32 SARS2 Eleanor Williams commented on gene: SARS2
Renal tubulopathies v2.32 HNF4A Eleanor Williams commented on gene: HNF4A
Renal tubulopathies v2.32 CLDN10 Eleanor Williams commented on gene: CLDN10: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Renal tubulopathies v2.31 VPS33B Eleanor Williams Source Expert Review Green was added to VPS33B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.31 VIPAS39 Eleanor Williams Source Expert Review Green was added to VIPAS39.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.31 SLC2A2 Eleanor Williams Source Expert Review Green was added to SLC2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.31 SARS2 Eleanor Williams Source Expert Review Green was added to SARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.31 HNF4A Eleanor Williams Source Expert Review Green was added to HNF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.31 CLDN10 Eleanor Williams Source Expert Review Green was added to CLDN10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v2.30 SEC61A1 Detlef Bockenhauer gene: SEC61A1 was added
gene: SEC61A1 was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61A1 were set to PMID: 33185949; 27392076; 31488840
Phenotypes for gene: SEC61A1 were set to hyporeninaemic hypoaldosteronism; autosomal dominant tubulointerstitial kidney disease
Penetrance for gene: SEC61A1 were set to Complete
Review for gene: SEC61A1 was set to GREEN
Added comment: very few patients/families reported so far, so "green" status should be reviewed carefully
Sources: Literature
Renal tubulopathies v2.30 AVPR2 Eleanor Williams Tag Skewed X-inactivation tag was added to gene: AVPR2.
Renal tubulopathies v2.30 AVPR2 Eleanor Williams Phenotypes for gene: AVPR2 were changed from Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation); Nephrogenic syndrome of inappropriate antidiuresis, 300539 to Diabetes insipidus, nephrogenic, OMIM:304800; Nephrogenic syndrome of inappropriate antidiuresis, OMIM:300539
Renal tubulopathies v2.29 AVPR2 Eleanor Williams Added comment: Comment on mode of pathogenicity: Gain of function variants
Renal tubulopathies v2.29 AVPR2 Eleanor Williams Mode of pathogenicity for gene: AVPR2 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Renal tubulopathies v2.28 EHHADH Arina Puzriakova Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615 to ?Fanconi renotubular syndrome 3, OMIM:615605; L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine
Renal tubulopathies v2.27 ATP6V0A4 Arina Puzriakova Publications for gene: ATP6V0A4 were set to
Renal tubulopathies v2.26 ATP6V0A4 Arina Puzriakova Phenotypes for gene: ATP6V0A4 were changed from Distal Renal Tubular Acidosis, Recessive; Renal tubular acidosis, distal, autosomal recessive, 602722; Distal renal tubular acidosis; Autosomal recessive distal renal tubular acidosis to Distal renal tubular acidosis 3, with or without sensorineural hearing loss, OMIM:602722
Renal tubulopathies v2.25 KCNJ16 Zornitza Stark gene: KCNJ16 was added
gene: KCNJ16 was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: KCNJ16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ16 were set to 33811157; 33840812
Phenotypes for gene: KCNJ16 were set to Renal tubulopathy; deafness
Review for gene: KCNJ16 was set to GREEN
Added comment: 8 unrelated families reported.
Sources: Literature
Renal tubulopathies v2.25 SLC5A2 Eleanor Williams Tag for-review was removed from gene: SLC5A2.
Renal tubulopathies v2.25 SLC5A2 Eleanor Williams Classified gene: SLC5A2 as Green List (high evidence)
Renal tubulopathies v2.25 SLC5A2 Eleanor Williams Added comment: Comment on list classification: Reverting this gene to green. It was green at the initial sign off (v2.3 in Feb 2020) and was reverted to amber in error in October 2020 before re-sign off.
Renal tubulopathies v2.25 SLC5A2 Eleanor Williams Gene: slc5a2 has been classified as Green List (High Evidence).
Renal tubulopathies v2.24 VPS33B Arina Puzriakova Tag for-review tag was added to gene: VPS33B.
Renal tubulopathies v2.24 Arina Puzriakova Panel version has been signed off
Renal tubulopathies v2.22 SLC2A2 Arina Puzriakova Classified gene: SLC2A2 as Amber List (moderate evidence)
Renal tubulopathies v2.22 SLC2A2 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version, will be examined at next panel review.
Renal tubulopathies v2.22 SLC2A2 Arina Puzriakova Gene: slc2a2 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.21 SLC5A2 Ivone Leong Tag for-review tag was added to gene: SLC5A2.
Renal tubulopathies v2.21 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
Renal tubulopathies v2.20 VIPAS39 Catherine Snow Tag for-review tag was added to gene: VIPAS39.
Renal tubulopathies v2.20 VPS33B Catherine Snow Classified gene: VPS33B as Amber List (moderate evidence)
Renal tubulopathies v2.20 VPS33B 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.
Renal tubulopathies v2.20 VPS33B Catherine Snow Gene: vps33b has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.19 VIPAS39 Catherine Snow Classified gene: VIPAS39 as Amber List (moderate evidence)
Renal tubulopathies v2.19 VIPAS39 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.
Renal tubulopathies v2.19 VIPAS39 Catherine Snow Gene: vipas39 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.18 SLC5A2 Catherine Snow Classified gene: SLC5A2 as Amber List (moderate evidence)
Renal tubulopathies v2.18 SLC5A2 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.
Renal tubulopathies v2.18 SLC5A2 Catherine Snow Gene: slc5a2 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.17 HNF4A Catherine Snow Classified gene: HNF4A as Amber List (moderate evidence)
Renal tubulopathies v2.17 HNF4A 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.
Renal tubulopathies v2.17 HNF4A Catherine Snow Gene: hnf4a has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.16 CLDN10 Catherine Snow Classified gene: CLDN10 as Amber List (moderate evidence)
Renal tubulopathies v2.16 CLDN10 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.
Renal tubulopathies v2.16 CLDN10 Catherine Snow Gene: cldn10 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.15 SARS2 Sarah Leigh edited their review of gene: SARS2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Renal tubulopathies v2.15 SARS2 Sarah Leigh Classified gene: SARS2 as Amber List (moderate evidence)
Renal tubulopathies v2.15 SARS2 Sarah Leigh Added comment: Comment on list classification: Associated with Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845 in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in at least 3 unrelated cases, together with supportive functional studies and segregation with the phenotype.
Renal tubulopathies v2.15 SARS2 Sarah Leigh Gene: sars2 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v2.14 SARS2 Sarah Leigh Tag for-review tag was added to gene: SARS2.
Renal tubulopathies v2.14 SARS2 Sarah Leigh gene: SARS2 was added
gene: SARS2 was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to 21255763; 24034276; 27279129
Phenotypes for gene: SARS2 were set to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845; Progressive Spastic Paresis
Review for gene: SARS2 was set to AMBER
Added comment: Sources: Literature
Renal tubulopathies v2.13 SLC2A2 Eleanor Williams Tag for-review tag was added to gene: SLC2A2.
Renal tubulopathies v2.13 HNF4A Eleanor Williams Tag for-review tag was added to gene: HNF4A.
Renal tubulopathies v2.13 CLDN10 Eleanor Williams Tag for-review tag was added to gene: CLDN10.
Renal tubulopathies v2.13 VPS33B Eleanor Williams Classified gene: VPS33B as Green List (high evidence)
Renal tubulopathies v2.13 VPS33B Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Sufficient cases and Renal tubular acidosis and Renal Fanconi syndrome are a feature of this syndrome
Renal tubulopathies v2.13 VPS33B Eleanor Williams Gene: vps33b has been classified as Green List (High Evidence).
Renal tubulopathies v2.12 VPS33B Eleanor Williams gene: VPS33B was added
gene: VPS33B was added to Renal tubulopathies. Sources: Literature
Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33B were set to 8151641; 16155421; 16896922
Phenotypes for gene: VPS33B were set to Arthrogryposis, renal dysfunction, and cholestasis 1 #208085
Review for gene: VPS33B was set to GREEN
Added comment: Associated with Arthrogryposis, renal dysfunction, and cholestasis 1 #208085 (AR) in OMIM.
Many reported cases listed in OMIM. Renal tubular acidosis and Renal Fanconi syndrome are listed as clinical features. VIPAS39 & VPS33B form a complex.
Sources: Literature
Renal tubulopathies v2.11 VIPAS39 Eleanor Williams Classified gene: VIPAS39 as Green List (high evidence)
Renal tubulopathies v2.11 VIPAS39 Eleanor Williams Added comment: Comment on list classification: Sufficient cases (>3) reported in PMID:20190753 with patients with different ethnicities, several variants are reported and functional studies support the phenotype.
Renal tubulopathies v2.11 VIPAS39 Eleanor Williams Gene: vipas39 has been classified as Green List (High Evidence).
Renal tubulopathies v2.10 VIPAS39 Eleanor Williams gene: VIPAS39 was added
gene: VIPAS39 was added to Renal tubulopathies. Sources: Expert Review
Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VIPAS39 were set to 20190753
Phenotypes for gene: VIPAS39 were set to Arthrogryposis, renal dysfunction, and cholestasis 2 #613404
Review for gene: VIPAS39 was set to GREEN
Added comment: Reviewed by Zornitza Stark on the Unexplained kidney failure in young people panel (panel 156) where she notes that it is a syndromic disorder with a prominent renal phenotype renal tubular acidosis and Fanconi syndrome. Australian Genomics have this gene green on their renal tubulopathies panel.
Sources: Expert Review
Renal tubulopathies v2.9 CLDN10 Catherine Snow Classified gene: CLDN10 as Green List (high evidence)
Renal tubulopathies v2.9 CLDN10 Catherine Snow Added comment: Comment on list classification: Following additional review from Zornitza and review in PMID: 31671507 relating to CLDN10 and HELIX syndrome. Enough evidence to promote CLDN10 to Green.
Renal tubulopathies v2.9 CLDN10 Catherine Snow Gene: cldn10 has been classified as Green List (High Evidence).
Renal tubulopathies v2.8 CLDN10 Catherine Snow Publications for gene: CLDN10 were set to 19307729
Renal tubulopathies v2.7 SLC2A2 Catherine Snow Classified gene: SLC2A2 as Green List (high evidence)
Renal tubulopathies v2.7 SLC2A2 Catherine Snow Added comment: Comment on list classification: SLC2A2 (GLUT2) associated with Fanconi-Bickel syndrome which includes renal tubular dysfunction. Sufficient number of unrelated individuals reported to classify as Green. Identified in PMID: 32150856 as missing from the panel in 27/02/2020.
Renal tubulopathies v2.7 SLC2A2 Catherine Snow Gene: slc2a2 has been classified as Green List (High Evidence).
Renal tubulopathies v2.6 SLC2A2 Catherine Snow Publications for gene: SLC2A2 were set to 32150856; 24175243
Renal tubulopathies v2.5 SLC2A2 Catherine Snow Publications for gene: SLC2A2 were set to
Renal tubulopathies v2.4 HNF4A Catherine Snow Classified gene: HNF4A as Green List (high evidence)
Renal tubulopathies v2.4 HNF4A Catherine Snow Added comment: Comment on list classification: HNF4A sufficient individuals who are unrelated and from different populations in the literature to classify this as Green. Variable phenotype reported although currently only one variant p.R63W. PMID 28458902 reported a patients with the variant and reviewed other published case.
Renal tubulopathies v2.4 HNF4A Catherine Snow Gene: hnf4a has been classified as Green List (High Evidence).
Renal tubulopathies v2.3 Sarah Leigh Panel version has been signed off
Renal tubulopathies v2.0 CLDN10 Zornitza Stark reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HELIX syndrome, MIM# 617671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v2.0 SLC2A2 Zornitza Stark gene: SLC2A2 was added
gene: SLC2A2 was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A2 were set to Fanconi-Bickel syndrome, MIM# 227810
Review for gene: SLC2A2 was set to GREEN
Added comment: Well established renal tubulopathy gene.
Sources: Expert list
Renal tubulopathies v2.0 HNF4A Zornitza Stark gene: HNF4A was added
gene: HNF4A was added to Renal tubulopathies. Sources: Expert list
Mode of inheritance for gene: HNF4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNF4A were set to 22802087; 24285859; 30005691; 28458902; 31875549
Phenotypes for gene: HNF4A were set to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, MIM#616026
Review for gene: HNF4A was set to GREEN
gene: HNF4A was marked as current diagnostic
Added comment: Multiple individuals reported.
Sources: Expert list
Renal tubulopathies v2.0 Eleanor Williams promoted panel to version 2.0
Renal tubulopathies v1.196 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Renal tubulopathies v1.195 CLDN16 Eleanor Williams changed review comment from: Comment on list classification: Changing rating from red to amber. Many cases reported in OMIM.; to: Comment on list classification: Changing rating from red to green. Many cases reported in OMIM.
Renal tubulopathies v1.195 SCNN1B Eleanor Williams Added comment: Comment on mode of inheritance: Updating the mode of inheritance as both Pseudohypoaldosteronism, type I (biallelic) and Liddle syndrome 1 (monoallelic) are relevant to the panel
Renal tubulopathies v1.195 SCNN1B Eleanor Williams Mode of inheritance for gene: SCNN1B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.194 SCNN1G Eleanor Williams Added comment: Comment on mode of inheritance: Updating the MOI as both Pseudohypoaldosteronism, type I (biallelic) and Liddle syndrome 2 (monoallelic) are relevant to the panel.
Renal tubulopathies v1.194 SCNN1G Eleanor Williams Mode of inheritance for gene: SCNN1G was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.193 GATM Eleanor Williams Mode of pathogenicity for gene: GATM was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Renal tubulopathies v1.192 AVPR2 Eleanor Williams Added comment: Comment on mode of pathogenicity: From Emma Ashton - NSIAD caused by gain of function mutations (mainly codon 137)
Renal tubulopathies v1.192 AVPR2 Eleanor Williams Mode of pathogenicity for gene: AVPR2 was changed from None to Other
Renal tubulopathies v1.191 AVPR2 Eleanor Williams commented on gene: AVPR2: Note: left mode of inheritance as X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males as there are reports of heterozygous females with NDI due to X-inactivation.
Renal tubulopathies v1.191 SCNN1G Eleanor Williams Publications for gene: SCNN1G were set to 8640238; 29582446
Renal tubulopathies v1.190 SCNN1G Eleanor Williams Classified gene: SCNN1G as Green List (high evidence)
Renal tubulopathies v1.190 SCNN1G Eleanor Williams Added comment: Comment on list classification: Changing rating from Amber to Green as the Liddle syndrome cases are relevant to this panel.
Renal tubulopathies v1.190 SCNN1G Eleanor Williams Gene: scnn1g has been classified as Green List (High Evidence).
Renal tubulopathies v1.189 SCNN1G Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

OMIM reports that in PMID: 8640238 - Strautnieks et al. 1996 - describe the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

PMID: 29582446 - Turan et al 2018 - report a homozygous missense variant (p.A63P) that they classify as a VUS in SCNN1G in a patient (patient 5) with aldosterone defects.

Also associated with Liddle syndrome 2 in OMIM which has Hypokalemia as a clinical feature.
; to: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

OMIM reports that in PMID: 8640238 - Strautnieks et al. 1996 - describe the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

PMID: 29582446 - Turan et al 2018 - report a homozygous missense variant (p.A63P) that they classify as a VUS in SCNN1G in a patient (patient 5) with aldosterone defects.

Also associated with Liddle syndrome 2 in OMIM which has Hypokalemia as a clinical feature. More than 3 cases reported.
Renal tubulopathies v1.189 GNA11 Eleanor Williams Classified gene: GNA11 as Green List (high evidence)
Renal tubulopathies v1.189 GNA11 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.189 GNA11 Eleanor Williams Gene: gna11 has been classified as Green List (High Evidence).
Renal tubulopathies v1.188 GNA11 Eleanor Williams changed review comment from: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - in a large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus. They note that hypercalciuria is not a prominent clinical feature in the affected patients in this kindred (Table 1) or in the two unrelated patients with sporadic hypoparathyroidism due to GNA11 mutations (R181Q and Phe341Leu) recently described by Nesbit et al

PMID: 23802516 - Nesbit et al 2013 - report a kindred with familial hypocalciuric hypercalcemia type 2 with an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia with a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were also detected in two unrelated patients with hypocalcemia. ; to: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family.

PMID: 24823460 - Li et al 2014 - in a large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus. They note that hypercalciuria is not a prominent clinical feature in the affected patients in this kindred or in the two unrelated patients with sporadic hypoparathyroidism due to GNA11 mutations (R181Q and Phe341Leu) recently described by Nesbit et al

PMID: 23802516 - Nesbit et al 2013 - report a kindred with familial hypocalciuric hypercalcemia type 2 with an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia with a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were also detected in two unrelated patients with hypocalcemia.
Renal tubulopathies v1.188 WNK4 Eleanor Williams Classified gene: WNK4 as Green List (high evidence)
Renal tubulopathies v1.188 WNK4 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported
Renal tubulopathies v1.188 WNK4 Eleanor Williams Gene: wnk4 has been classified as Green List (High Evidence).
Renal tubulopathies v1.187 WNK4 Eleanor Williams Publications for gene: WNK4 were set to
Renal tubulopathies v1.186 WNK4 Eleanor Williams Mode of inheritance for gene: WNK4 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.185 WNK4 Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type IIB #614491 in OMIM.

PMID: 11498583 - Wilson et al. 2001 - Examination of WNK4 in PHAII kindreds identified four missense mutations, all of
which cosegregated with the disease.Three of these are charge-changing substitutions that cluster in a span of four amino acids within a negatively charged 10-amino acid segment that is highly conserved among all members of the WNK family in human as well as orthologs in mouse and rat; to: Associated with Pseudohypoaldosteronism, type IIB #614491 in OMIM.

PMID: 11498583 - Wilson et al. 2001 - Examination of WNK4 in PHAII kindreds identified four missense mutations, all of which cosegregated with the disease.Three of these are charge-changing substitutions that cluster in a span of four amino acids within a negatively charged 10-amino acid segment that is highly conserved among all members of the WNK family in human as well as orthologs in mouse and rat
Renal tubulopathies v1.185 WNK1 Eleanor Williams Classified gene: WNK1 as Amber List (moderate evidence)
Renal tubulopathies v1.185 WNK1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber as two cases (both with deletions) have been reported.
Renal tubulopathies v1.185 WNK1 Eleanor Williams Gene: wnk1 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.184 WNK1 Eleanor Williams Publications for gene: WNK1 were set to
Renal tubulopathies v1.183 WNK1 Eleanor Williams Added comment: Comment on phenotypes: Removed a phenotype that I think is not relevant to this panel.
Renal tubulopathies v1.183 WNK1 Eleanor Williams Phenotypes for gene: WNK1 were changed from Pseudohypoaldosteronism, type IIC, 614492; Neuropathy, hereditary sensory and autonomic, type II, 201300 (AR) to Pseudohypoaldosteronism, type IIC, 614492
Renal tubulopathies v1.182 WNK1 Eleanor Williams Mode of inheritance for gene: WNK1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.181 UMOD Eleanor Williams Classified gene: UMOD as Green List (high evidence)
Renal tubulopathies v1.181 UMOD Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.181 UMOD Eleanor Williams Gene: umod has been classified as Green List (High Evidence).
Renal tubulopathies v1.180 UMOD Eleanor Williams Publications for gene: UMOD were set to
Renal tubulopathies v1.179 UMOD Eleanor Williams Mode of inheritance for gene: UMOD was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.178 TRPM6 Eleanor Williams Classified gene: TRPM6 as Green List (high evidence)
Renal tubulopathies v1.178 TRPM6 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.178 TRPM6 Eleanor Williams Gene: trpm6 has been classified as Green List (High Evidence).
Renal tubulopathies v1.177 TRPM6 Eleanor Williams Classified gene: TRPM6 as Red List (low evidence)
Renal tubulopathies v1.177 TRPM6 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.177 TRPM6 Eleanor Williams Gene: trpm6 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.176 TRPM6 Eleanor Williams Publications for gene: TRPM6 were set to 12032568
Renal tubulopathies v1.175 SLC9A3R1 Eleanor Williams Publications for gene: SLC9A3R1 were set to
Renal tubulopathies v1.174 SLC9A3R1 Eleanor Williams Classified gene: SLC9A3R1 as Red List (low evidence)
Renal tubulopathies v1.174 SLC9A3R1 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as hypophosphatemia is covered by the 'R154 Hypophosphataemia or rickets' panel where it is rated amber.
Renal tubulopathies v1.174 SLC9A3R1 Eleanor Williams Gene: slc9a3r1 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.173 SLC9A3R1 Eleanor Williams changed review comment from: Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 in OMIM.

PubMed: 18784102 - Karim et al 2008 - sequenced the NHERF1 gene (now called SLC9A3R1) in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. They identified three distinct heterozygous missense mutations in the NHERF1 gene in four unrelated patients. All four patients with NHERF1 mutations had TmP/GFR values below the lower limit of the normal range, as well as hypophosphatemia. Patients 1, 3, and 4 also had recurrent nephrolithiasis. The four patients with mutations did not have proximal-tubule dysfunction other than the low TmP/GFR value. The results identify NHERF1 mutations as a cause of renal phosphate loss that may increase the risk of renal stone formation or bone demineralization: the mutations were identified only in patients with TmP/GFR values that were below normal and significantly lower than those in patients in whom mutations were not identified; to: Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 in OMIM.

PubMed: 18784102 - Karim et al 2008 - sequenced the NHERF1 gene (now called SLC9A3R1) in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. They identified three distinct heterozygous missense mutations (328C->G, L110V; 458G->A,R153Q;673G->A,E225K) in the NHERF1 gene in four unrelated patients. All four patients with NHERF1 mutations had TmP/GFR values below the lower limit of the normal range, as well as hypophosphatemia. Patients 1, 3, and 4 also had recurrent nephrolithiasis. The four patients with mutations did not have proximal-tubule dysfunction other than the low TmP/GFR value. The results identify NHERF1 mutations as a cause of renal phosphate loss that may increase the risk of renal stone formation or bone demineralization: the mutations were identified only in patients with TmP/GFR values that were below normal and significantly lower than those in patients in whom mutations were not identified

PMID: 25296721 - Halbritter et al 2015 - identify pathogenic heterozygous variants in SLC9A3R1 in 2 families. c.673G>A, p.Glu225Lys and c.888+2T>C, 5′ splice site (new variant).

PMID: 19073985 - Bergwitz et al 2008 - report that 2 of the variants (328C->G and 458G->A) reported by Karim et al 2008 are listed as single-nucleotide polymorphisms in the National Center for Biotechnology Information dbSNP, Ensembl, and GeneCards databases with an allele frequency of 0.01 and 0.03.

Amber rating suggested.
Renal tubulopathies v1.173 SLC9A3R1 Eleanor Williams Mode of inheritance for gene: SLC9A3R1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.172 SLC5A2 Eleanor Williams Classified gene: SLC5A2 as Green List (high evidence)
Renal tubulopathies v1.172 SLC5A2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as >3 cases reported.
Renal tubulopathies v1.172 SLC5A2 Eleanor Williams Gene: slc5a2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.171 SLC5A2 Eleanor Williams Publications for gene: SLC5A2 were set to
Renal tubulopathies v1.170 SLC5A2 Eleanor Williams Mode of inheritance for gene: SLC5A2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.169 SLC34A3 Eleanor Williams Publications for gene: SLC34A3 were set to
Renal tubulopathies v1.168 SLC34A3 Eleanor Williams Classified gene: SLC34A3 as Red List (low evidence)
Renal tubulopathies v1.168 SLC34A3 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as hypophosphatemia is covered by the 'R154 Hypophosphataemia or rickets' panel.
Renal tubulopathies v1.168 SLC34A3 Eleanor Williams Gene: slc34a3 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.167 SLC34A3 Eleanor Williams Mode of inheritance for gene: SLC34A3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.166 SLC34A1 Eleanor Williams Classified gene: SLC34A1 as Red List (low evidence)
Renal tubulopathies v1.166 SLC34A1 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as hypophosphatemia is covered by the 'R154 Hypophosphataemia or rickets' panel.
Renal tubulopathies v1.166 SLC34A1 Eleanor Williams Gene: slc34a1 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.165 SLC34A1 Eleanor Williams Publications for gene: SLC34A1 were set to
Renal tubulopathies v1.164 SLC34A1 Eleanor Williams Mode of inheritance for gene: SLC34A1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.163 SLC2A9 Eleanor Williams Classified gene: SLC2A9 as Green List (high evidence)
Renal tubulopathies v1.163 SLC2A9 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.163 SLC2A9 Eleanor Williams Gene: slc2a9 has been classified as Green List (High Evidence).
Renal tubulopathies v1.162 SLC2A9 Eleanor Williams Publications for gene: SLC2A9 were set to
Renal tubulopathies v1.161 SLC2A9 Eleanor Williams Mode of inheritance for gene: SLC2A9 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.160 SLC22A12 Eleanor Williams Classified gene: SLC22A12 as Green List (high evidence)
Renal tubulopathies v1.160 SLC22A12 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.160 SLC22A12 Eleanor Williams Gene: slc22a12 has been classified as Green List (High Evidence).
Renal tubulopathies v1.159 SLC22A12 Eleanor Williams Publications for gene: SLC22A12 were set to
Renal tubulopathies v1.158 SLC22A12 Eleanor Williams Mode of inheritance for gene: SLC22A12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.157 SCNN1G Eleanor Williams Classified gene: SCNN1G as Amber List (moderate evidence)
Renal tubulopathies v1.157 SCNN1G Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber. 3 cases of Pseudohypoaldosteronism are linked with possible founder effect mutation, 1 other cases. GMS submitted gene with Pseudohypoaldosteronism phenotype only listed. Variants in the gene also linked with Liddle syndrome 2 which may also be relevant to this panel.
Renal tubulopathies v1.157 SCNN1G Eleanor Williams Gene: scnn1g has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.156 SCNN1G Eleanor Williams Publications for gene: SCNN1G were set to
Renal tubulopathies v1.155 SCNN1G Eleanor Williams Mode of inheritance for gene: SCNN1G was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.154 SCNN1G Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

OMIM reports that in PMID: 8640238 - Strautnieks et al. 1996 - describe the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

PMID: 29582446 - Turan et al 2018 - report a homozygous missense variant (p.A63P) that they classify as a VUS in SCNN1G in a patient (patient 5) with aldosterone defects.; to: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

OMIM reports that in PMID: 8640238 - Strautnieks et al. 1996 - describe the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

PMID: 29582446 - Turan et al 2018 - report a homozygous missense variant (p.A63P) that they classify as a VUS in SCNN1G in a patient (patient 5) with aldosterone defects.

Also associated with Liddle syndrome 2 in OMIM which has Hypokalemia as a clinical feature.
Renal tubulopathies v1.154 SCNN1B Eleanor Williams Classified gene: SCNN1B as Green List (high evidence)
Renal tubulopathies v1.154 SCNN1B Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.154 SCNN1B Eleanor Williams Gene: scnn1b has been classified as Green List (High Evidence).
Renal tubulopathies v1.153 SCNN1B Eleanor Williams Added comment: Comment on mode of inheritance: Mode of inheritance is for Pseudohypoaldosteronism, type I, which is the phenotype listed by the GMS group.
Renal tubulopathies v1.153 SCNN1B Eleanor Williams Mode of inheritance for gene: SCNN1B was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.152 SCNN1B Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

PMID: 8589714 - Chang et al 1996 - report a Arabic kindred from Israel in which a homozygous missense mutation was found in betaENaC (G37S).

PMID: 26807262 - Nobel et al 2016 - report a 32-year-old female with pseudohypoaldosteronism type 1 with persistent, symptomatic hyperkalemia who was compound heterozygous for two variants in SCNN1B (c.1288delC and c.1466+1 G>A). .

PMID: 31301676 - Gopal-Kothandapani et al 2019 - Abstract only accessed - report a patient with PHA1 and a novel mutation in SCNN1B.

PMID: 31018202 - Cayir et al 2019 - Abstract only accessed - describe a consanguineous family with a child with systemic PHA1 and 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1B.; to: Associated with Liddle syndrome 1 #177200 (AD) and Pseudohypoaldosteronism, type I #264350 (AR) in OMIM.


Liddle syndrome 1 - 7 cases reported in OMIM.

Pseudohypoaldosteronism, type I :
PMID: 8589714 - Chang et al 1996 - report a Arabic kindred from Israel in which a homozygous missense mutation was found in betaENaC (G37S).

PMID: 26807262 - Nobel et al 2016 - report a 32-year-old female with pseudohypoaldosteronism type 1 with persistent, symptomatic hyperkalemia who was compound heterozygous for two variants in SCNN1B (c.1288delC and c.1466+1 G>A). .

PMID: 31301676 - Gopal-Kothandapani et al 2019 - Abstract only accessed - report a patient with PHA1 and a novel mutation in SCNN1B.

PMID: 31018202 - Cayir et al 2019 - Abstract only accessed - describe a consanguineous family with a child with systemic PHA1 and 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1B.
Renal tubulopathies v1.152 SCNN1B Eleanor Williams Phenotypes for gene: SCNN1B were changed from genes for Liddle, GRA, PHA1, hypomagnesemia without stones, AME are all missing; Pseudohypoaldosteronism, type I, 264350 to Pseudohypoaldosteronism, type I, 264350
Renal tubulopathies v1.151 SCNN1B Eleanor Williams Publications for gene: SCNN1B were set to
Renal tubulopathies v1.150 SCNN1B Eleanor Williams Mode of inheritance for gene: SCNN1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.149 SCNN1B Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

PMID: 8589714 - Chang et al 1996 - report a Arabic kindred from Israel in which a homozygous missense mutation was found in betaENaC (G37S).

PMID: 26807262 - Nobel et al 2016 - report a 32-year-old female with pseudohypoaldosteronism type 1 with persistent, symptomatic hyperkalemia who was compound heterozygous for two variants in SCNN1B (c.1288delC and c.1466+1 G>A). .

PMID: 31301676 - Gopal-Kothandapani et al 2019 - Abstract only accessed - report a patient with PHA1 and a novel mutation in SCNN1B.; to: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

PMID: 8589714 - Chang et al 1996 - report a Arabic kindred from Israel in which a homozygous missense mutation was found in betaENaC (G37S).

PMID: 26807262 - Nobel et al 2016 - report a 32-year-old female with pseudohypoaldosteronism type 1 with persistent, symptomatic hyperkalemia who was compound heterozygous for two variants in SCNN1B (c.1288delC and c.1466+1 G>A). .

PMID: 31301676 - Gopal-Kothandapani et al 2019 - Abstract only accessed - report a patient with PHA1 and a novel mutation in SCNN1B.

PMID: 31018202 - Cayir et al 2019 - Abstract only accessed - describe a consanguineous family with a child with systemic PHA1 and 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1B.
Renal tubulopathies v1.149 SCNN1A Eleanor Williams Classified gene: SCNN1A as Green List (high evidence)
Renal tubulopathies v1.149 SCNN1A Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.149 SCNN1A Eleanor Williams Gene: scnn1a has been classified as Green List (High Evidence).
Renal tubulopathies v1.148 SCNN1A Eleanor Williams Publications for gene: SCNN1A were set to
Renal tubulopathies v1.147 SCNN1A Eleanor Williams Mode of inheritance for gene: SCNN1A was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.146 REN Eleanor Williams Classified gene: REN as Green List (high evidence)
Renal tubulopathies v1.146 REN Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as > 3 cases reported.
Renal tubulopathies v1.146 REN Eleanor Williams Gene: ren has been classified as Green List (High Evidence).
Renal tubulopathies v1.145 REN Eleanor Williams Publications for gene: REN were set to
Renal tubulopathies v1.144 REN Eleanor Williams Added comment: Comment on mode of inheritance: Hyperuricemic nephropathy, familial juvenile 2 shows monoallelic and Renal tubular dysgenesis show biallelic inheritance.
Renal tubulopathies v1.144 REN Eleanor Williams Mode of inheritance for gene: REN was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.143 REN Eleanor Williams Mode of inheritance for gene: REN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.142 OCRL Eleanor Williams Publications for gene: OCRL were set to
Renal tubulopathies v1.141 OCRL Eleanor Williams Mode of inheritance for gene: OCRL was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal tubulopathies v1.140 OCRL Eleanor Williams Classified gene: OCRL as Red List (low evidence)
Renal tubulopathies v1.140 OCRL Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as Dent disease is covered by the 'R256 Nephrocalcinosis or nephrolithiasis' panel.
Renal tubulopathies v1.140 OCRL Eleanor Williams Gene: ocrl has been classified as Red List (Low Evidence).
Renal tubulopathies v1.139 NR3C2 Eleanor Williams Classified gene: NR3C2 as Green List (high evidence)
Renal tubulopathies v1.139 NR3C2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases have been reported.
Renal tubulopathies v1.139 NR3C2 Eleanor Williams Gene: nr3c2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.138 NR3C2 Eleanor Williams Added comment: Comment on mode of inheritance: Only one report of biallelic mutations, and in that case there were 3 in the patient, and were reported to occur in healthy populations
Renal tubulopathies v1.138 NR3C2 Eleanor Williams Mode of inheritance for gene: NR3C2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.137 NR3C2 Eleanor Williams Publications for gene: NR3C2 were set to
Renal tubulopathies v1.136 NR3C2 Eleanor Williams changed review comment from: Associated with Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy #605115 and
Pseudohypoaldosteronism type I, autosomal dominant #177735 in OMIM.

The gene is also known as MCR.
Many cases of Pseudohypoaldosteronism associated with variants in NR3C2 reported in OMIM.; to: Associated with Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy #605115 and Pseudohypoaldosteronism type I, autosomal dominant #177735 in OMIM.

The gene is also known as MCR.

Many cases of Pseudohypoaldosteronism associated with variants in NR3C2 reported in OMIM.

No inheritance pattern listed in OMIM. However, most reports are for monoallelic inheritance (PMID: 9662404, 12788847, 16972228, 16954160). The only report of a biallelic case (PMID: 12483305 Arai et al 2003) was found in In a Japanese patient with sporadic PHA. 3 homozygous substitutions were found that had previously been reported to occur in healthy populations. The authors suggested that 2 or more 'functional' polymorphisms, any of which exhibits only slight effects on function alone and is incapable of causing PHA, may in the right allelic combination induce the negative salt conservation characteristic of PHA.
Renal tubulopathies v1.136 MAGED2 Eleanor Williams Classified gene: MAGED2 as Green List (high evidence)
Renal tubulopathies v1.136 MAGED2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases have been reported.
Renal tubulopathies v1.136 MAGED2 Eleanor Williams Gene: maged2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.135 MAGED2 Eleanor Williams Added comment: Comment on mode of inheritance: Note - no cases reported in females to date.
Renal tubulopathies v1.135 MAGED2 Eleanor Williams Mode of inheritance for gene: MAGED2 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal tubulopathies v1.134 MAGED2 Eleanor Williams changed review comment from: Associated with Bartter syndrome, type 5, antenatal, transient #300971 in OMIM.

Laghmani et al. (2016) - identified variants in MAGED2 in 13 infants from 9 families who had transient antenatal Bartter's syndrome. All affected infants were male. They observed prominent tubular expression of MAGE-D2 in the human fetal renal cortex. In total, seven truncating mutations (two nonsense, two frameshift, and three splice-site mutations) and two nontruncating mutations (one missense and one in-frame deletion) were identified.; to: Associated with Bartter syndrome, type 5, antenatal, transient #300971 in OMIM.

PMID: 27120771 - Laghmani et al. (2016) - identified variants in MAGED2 in 13 infants from 9 families who had transient antenatal Bartter's syndrome. All affected infants were male. They observed prominent tubular expression of MAGE-D2 in the human fetal renal cortex. In total, seven truncating mutations (two nonsense, two frameshift, and three splice-site mutations) and two nontruncating mutations (one missense and one in-frame deletion) were identified.
Renal tubulopathies v1.134 KLHL3 Eleanor Williams Classified gene: KLHL3 as Green List (high evidence)
Renal tubulopathies v1.134 KLHL3 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases reported.
Renal tubulopathies v1.134 KLHL3 Eleanor Williams Gene: klhl3 has been classified as Green List (High Evidence).
Renal tubulopathies v1.133 KLHL3 Eleanor Williams Publications for gene: KLHL3 were set to
Renal tubulopathies v1.132 KLHL3 Eleanor Williams Mode of inheritance for gene: KLHL3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.131 KLHL3 Eleanor Williams changed review comment from: Associated with Pseudohypoaldosteronism, type IID 614495 in OMIM.
Many reports of cases in OMIM. Both monoallelic and biallelic.; to: Associated with Pseudohypoaldosteronism, type IID 614495 in OMIM.
Many reports of cases in OMIM. Both monoallelic and biallelic.

PMID: 22266938 - Boyden et al 2012 - report on a cohort of 52 PHAII kindreds including 126 affected subjects with renal hyperkalemia and otherwise normal renal function; hypertension and acidosis were present in 71% and 82%, respectively. They identified both dominant and recessive mutations in the KLHL3 gene.

PMID: 22406640 - Louis-Dit-Picard et al 2012 - report missense mutations in the KLHL3 gene in affected individuals from 16 families with hyperkalemic hypertension (out of 45 investigated). The variants were present in heterozygosity in 12 of the families and in homozygosity in 4.
Renal tubulopathies v1.131 KCNJ10 Eleanor Williams Classified gene: KCNJ10 as Green List (high evidence)
Renal tubulopathies v1.131 KCNJ10 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases reported in OMIM.
Renal tubulopathies v1.131 KCNJ10 Eleanor Williams Gene: kcnj10 has been classified as Green List (High Evidence).
Renal tubulopathies v1.130 KCNJ10 Eleanor Williams Publications for gene: KCNJ10 were set to
Renal tubulopathies v1.129 KCNJ10 Eleanor Williams Added comment: Comment on phenotypes: Removed phenotype that does not have renal presentation
Renal tubulopathies v1.129 KCNJ10 Eleanor Williams Phenotypes for gene: KCNJ10 were changed from SESAME/EAST syndrome, 612780; Enlarged vestibular aqueduct, digenic, 600791 to SESAME/EAST syndrome, 612780
Renal tubulopathies v1.128 KCNJ10 Eleanor Williams Phenotypes for gene: KCNJ10 were changed from SESAME/EAST syndrome, 612780; Enlarged vestibular aqueduct, digenic, 60079 to SESAME/EAST syndrome, 612780; Enlarged vestibular aqueduct, digenic, 600791
Renal tubulopathies v1.127 KCNJ10 Eleanor Williams Mode of inheritance for gene: KCNJ10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.126 HNF1B Eleanor Williams Classified gene: HNF1B as Green List (high evidence)
Renal tubulopathies v1.126 HNF1B Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as many cases reported in OMIM associated with Renal cysts and diabetes syndrome.
Renal tubulopathies v1.126 HNF1B Eleanor Williams Gene: hnf1b has been classified as Green List (High Evidence).
Renal tubulopathies v1.125 HNF1B Eleanor Williams Publications for gene: HNF1B were set to
Renal tubulopathies v1.124 HNF1B Eleanor Williams Mode of inheritance for gene: HNF1B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.123 HNF1B Eleanor Williams changed review comment from: Associated with Renal cysts and diabetes syndrome #137920 in OMIM.

Many cases reported in OMIM of cases with variants in HNF1B and Renal cysts and diabetes syndrome.; to: Associated with Renal cysts and diabetes syndrome #137920 in OMIM.

Many cases reported in OMIM of cases with variants in HNF1B and Renal cysts and diabetes syndrome.

Also PMID: 19389850 - Adalat et al 2009- report an index case of a 13 year old boy with renal malformation who presented with tetany and hypomagnesemia. He was found to have a heterozygous HNF1B deletion as did his sister and father who also were found to have cystic kidneys. The sister and brother had hypocalciuria, while the father had hypomagnesemia. Of 91 futher patients with renal malformations in which HNF1B was screened, 21 (23%) had a heterozygous HNF1B mutation. 12 cases had a heterozygous HNF1B deletion c.1_1674del; p.Met1_Trp557del from 10 different families. 9 patients from 8 different families had heterozygous mutations detected by direct sequencing; 3 cases had frame shift mutations, 5 cases from 4 families had splice-site mutations and 1 with a missense mutation. 44% (eight of 18) mut+ patients had hypomagnesemia versus 2% (one of 48) mut− patients.
Renal tubulopathies v1.123 GNA11 Eleanor Williams commented on gene: GNA11: Will check with clinicians as to whether this gene is relevant to the panel as it doesn't seem to have a strong renal phenotype.
Renal tubulopathies v1.123 GNA11 Eleanor Williams Publications for gene: GNA11 were set to
Renal tubulopathies v1.122 GNA11 Eleanor Williams Mode of inheritance for gene: GNA11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.121 GNA11 Eleanor Williams changed review comment from: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - in a large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus.; to: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - in a large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus. They note that hypercalciuria is not a prominent clinical feature in the affected patients in this kindred (Table 1) or in the two unrelated patients with sporadic hypoparathyroidism due to GNA11 mutations (R181Q and Phe341Leu) recently described by Nesbit et al

PMID: 23802516 - Nesbit et al 2013 - report a kindred with familial hypocalciuric hypercalcemia type 2 with an in-frame deletion of a conserved Gα11 isoleucine (Ile200del), and one of the nine unrelated patients with familial hypocalciuric hypercalcemia with a missense GNA11 mutation (Leu135Gln). Missense GNA11 mutations (Arg181Gln and Phe341Leu) were also detected in two unrelated patients with hypocalcemia.
Renal tubulopathies v1.121 GNA11 Eleanor Williams changed review comment from: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - ina large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus.; to: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - in a large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus.
Renal tubulopathies v1.121 GNA11 Eleanor Williams changed review comment from: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - ina large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature.The basis for this episode of transient diabetes insipidus remains unknown, and no other member of the extended family has ever manifested symptoms of diabetes insipidus.; to: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - ina large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature but no other member of the extended family has ever manifested symptoms of diabetes insipidus.
Renal tubulopathies v1.121 GNAS Eleanor Williams changed review comment from: Linked to several disease phenotypes in OMIM but they don't appear relevant to a renal disease.

PMID: 30312418 Biebermann et al 2018 - two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Both unrelated patients presented severe asymptomatic infantile hyponatremia, skeletal and growth plate abnormalities, early onset pubertal development, and apparent PTH resistance in the proximal but not in the distal renal tubules. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients.

They author say the clinical phenotype suggests a gain of function at the vasopressin 2 receptor (V2R) and lutropin/choriogonadotropin receptor (LHCGR), yet increased serum PTH concentrations indicative of impaired proximal tubular PTH1 receptor (PTH1R) function; to: Linked to several disease phenotypes in OMIM but they don't appear relevant to a renal disease.

PMID: 30312418 Biebermann et al 2018 - two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Both unrelated patients presented severe asymptomatic infantile hyponatremia, skeletal and growth plate abnormalities, early onset pubertal development, and apparent PTH resistance in the proximal but not in the distal renal tubules. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients.

They authors say the clinical phenotype suggests a gain of function at the vasopressin 2 receptor (V2R) and lutropin/choriogonadotropin receptor (LHCGR), yet increased serum PTH concentrations indicative of impaired proximal tubular PTH1 receptor (PTH1R) function
Renal tubulopathies v1.121 GNAS Eleanor Williams changed review comment from: Linked to several disease phenotypes in OMIM but they don't appear relevant to a renal disease.

PMID: 30312418 Biebermann et al 2018 - two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Both unrelated patients presented severe asymptomatic infantile hyponatremia, skeletal and growth plate abnormalities, early onset pubertal development, and apparent PTH resistance in the proximal but not in the distal renal tubules. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients.; to: Linked to several disease phenotypes in OMIM but they don't appear relevant to a renal disease.

PMID: 30312418 Biebermann et al 2018 - two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Both unrelated patients presented severe asymptomatic infantile hyponatremia, skeletal and growth plate abnormalities, early onset pubertal development, and apparent PTH resistance in the proximal but not in the distal renal tubules. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients.

They author say the clinical phenotype suggests a gain of function at the vasopressin 2 receptor (V2R) and lutropin/choriogonadotropin receptor (LHCGR), yet increased serum PTH concentrations indicative of impaired proximal tubular PTH1 receptor (PTH1R) function
Renal tubulopathies v1.121 GNAS Eleanor Williams Mode of inheritance for gene: GNAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Renal tubulopathies v1.120 GNAS Eleanor Williams Classified gene: GNAS as Amber List (moderate evidence)
Renal tubulopathies v1.120 GNAS Eleanor Williams Added comment: Comment on list classification: 2 cases reported in PMID: 30312418
Renal tubulopathies v1.120 GNAS Eleanor Williams Gene: gnas has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.119 GATM Eleanor Williams Classified gene: GATM as Green List (high evidence)
Renal tubulopathies v1.119 GATM Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases reported.
Renal tubulopathies v1.119 GATM Eleanor Williams Gene: gatm has been classified as Green List (High Evidence).
Renal tubulopathies v1.118 GATM Eleanor Williams Added comment: Comment on mode of pathogenicity: All missense variants reported to date. In silico analysis suggests that the variants result in an additional interaction interface
Renal tubulopathies v1.118 GATM Eleanor Williams Mode of pathogenicity for gene: GATM was changed from to None
Renal tubulopathies v1.117 GATM Eleanor Williams Mode of inheritance for gene: GATM was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.116 GATM Eleanor Williams changed review comment from: PMID: 29654216 (Reichold et al 2018) reports 5 families with with a novel form of autosomal dominant kidney disease characterized by renal tubular Fanconi syndrome early in life followed by progression to renal glomerular failure in mid-adulthood. All patients show monoallelic mutations in the gene GATM. 4 heterozygous missense mutations of evolutionary conserved amino acid residues in GATM were found (c.958C>T, p.P320S; c.1006A>G, p.T336A; c.1007C>T, p.T336I;
c.1022C>T, p.P341L). In each family, one variant segregated with the disorder and was fully penetrant. In silico analysis showed that the particular GATM mutations create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells.; to: PMID: 29654216 (Reichold et al 2018) reports 5 families with with a novel form of autosomal dominant kidney disease characterized by renal tubular Fanconi syndrome early in life followed by progression to renal glomerular failure in mid-adulthood. All patients show monoallelic mutations in the gene GATM. 4 heterozygous missense mutations of evolutionary conserved amino acid residues in GATM were found (c.958C>T, p.P320S; c.1006A>G, p.T336A; c.1007C>T, p.T336I; c.1022C>T, p.P341L). In each family, one variant segregated with the disorder and was fully penetrant. In silico analysis showed that the particular GATM mutations create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells.
Renal tubulopathies v1.116 FXYD2 Eleanor Williams Classified gene: FXYD2 as Amber List (moderate evidence)
Renal tubulopathies v1.116 FXYD2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber. 3 cases reported by all with the same variant which is likely a founder effect.
Renal tubulopathies v1.116 FXYD2 Eleanor Williams Gene: fxyd2 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.115 FXYD2 Eleanor Williams changed review comment from: Associated with Hypomagnesemia 2, renal #154020 in OMIM.


PMID: 11062458 - Meij et al 2000 - Identified a heterozygous mutation, 123G→A in FXYD2 in a large Dutch family with dominant hypomagnesaemia which cosegregated with the disorder. The mutation causes the substitution of the conserved glycine 41 within the putative transmembrane domain by arginine.

PMID: 2576584 - de Baaij et al 2015 - two families (Dutch and Belgian) with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. The same mutation as reported before was found in these families, c.115G>A, p.Gly41Arg, and haplotype analysis revealed an overlapping haplotype in all families, suggesting a founder effect.

3 cases but likely linked by common ancestor as same variant found in all three.; to: Associated with Hypomagnesemia 2, renal #154020 in OMIM.


PMID: 11062458 - Meij et al 2000 - Identified a heterozygous mutation, 123G→A in FXYD2 in a large Dutch family with dominant hypomagnesaemia which cosegregated with the disorder. The mutation causes the substitution of the conserved glycine 41 within the putative transmembrane domain by arginine.

PMID: 25765846 - de Baaij et al 2015 - two families (Dutch and Belgian) with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. The same mutation as reported before was found in these families, c.115G>A, p.Gly41Arg, and haplotype analysis revealed an overlapping haplotype in all families, suggesting a founder effect.

3 cases but likely linked by common ancestor as same variant found in all three.
Renal tubulopathies v1.115 FXYD2 Eleanor Williams Publications for gene: FXYD2 were set to
Renal tubulopathies v1.114 FXYD2 Eleanor Williams Mode of inheritance for gene: FXYD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.113 CYP24A1 Eleanor Williams Classified gene: CYP24A1 as Green List (high evidence)
Renal tubulopathies v1.113 CYP24A1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as more than 3 cases reported in OMIM.
Renal tubulopathies v1.113 CYP24A1 Eleanor Williams Gene: cyp24a1 has been classified as Green List (High Evidence).
Renal tubulopathies v1.112 CYP24A1 Eleanor Williams Added comment: Comment on publications: Publications from OMIM
Renal tubulopathies v1.112 CYP24A1 Eleanor Williams Publications for gene: CYP24A1 were set to
Renal tubulopathies v1.111 CYP24A1 Eleanor Williams Mode of inheritance for gene: CYP24A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.110 CUL3 Eleanor Williams Classified gene: CUL3 as Green List (high evidence)
Renal tubulopathies v1.110 CUL3 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases reported.
Renal tubulopathies v1.110 CUL3 Eleanor Williams Gene: cul3 has been classified as Green List (High Evidence).
Renal tubulopathies v1.109 CUL3 Eleanor Williams Publications for gene: CUL3 were set to
Renal tubulopathies v1.108 CUL3 Eleanor Williams Mode of inheritance for gene: CUL3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.107 CLDN19 Eleanor Williams changed review comment from: Associated with Hypomagnesemia 5, renal, with ocular involvement 248190 in OMIM.

Many cases reported in OMIM.; to: Associated with Hypomagnesemia 5, renal, with ocular involvement 248190 in OMIM.

Many cases reported in OMIM, but note some cases have the same variant - likely founder effect.
Renal tubulopathies v1.107 CLDN19 Eleanor Williams Publications for gene: CLDN19 were set to 17033971; 22422540
Renal tubulopathies v1.106 CLDN19 Eleanor Williams Classified gene: CLDN19 as Green List (high evidence)
Renal tubulopathies v1.106 CLDN19 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases reported in OMIM.
Renal tubulopathies v1.106 CLDN19 Eleanor Williams Gene: cldn19 has been classified as Green List (High Evidence).
Renal tubulopathies v1.105 CLDN19 Eleanor Williams Added comment: Comment on publications: Publications added from OMIM
Renal tubulopathies v1.105 CLDN19 Eleanor Williams Publications for gene: CLDN19 were set to
Renal tubulopathies v1.104 CLDN19 Eleanor Williams Mode of inheritance for gene: CLDN19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.103 CLDN16 Eleanor Williams Classified gene: CLDN16 as Green List (high evidence)
Renal tubulopathies v1.103 CLDN16 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber. Many cases reported in OMIM.
Renal tubulopathies v1.103 CLDN16 Eleanor Williams Gene: cldn16 has been classified as Green List (High Evidence).
Renal tubulopathies v1.102 CLDN16 Eleanor Williams Added comment: Comment on publications: Publications from OMIM.
Renal tubulopathies v1.102 CLDN16 Eleanor Williams Publications for gene: CLDN16 were set to 10390358; 10878661; 16528408; 16501001; 26426912
Renal tubulopathies v1.101 CLDN16 Eleanor Williams Publications for gene: CLDN16 were set to
Renal tubulopathies v1.100 CLDN16 Eleanor Williams Mode of inheritance for gene: CLDN16 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.99 CLDN10 Eleanor Williams Classified gene: CLDN10 as Amber List (moderate evidence)
Renal tubulopathies v1.99 CLDN10 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber. Two cases reported.
Renal tubulopathies v1.99 CLDN10 Eleanor Williams Gene: cldn10 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.98 CLDN10 Eleanor Williams Mode of inheritance for gene: CLDN10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.97 CLCNKA Eleanor Williams Classified gene: CLCNKA as Amber List (moderate evidence)
Renal tubulopathies v1.97 CLCNKA Eleanor Williams Added comment: Comment on list classification: 2 reported cases. But note disease association is digenic.
Renal tubulopathies v1.97 CLCNKA Eleanor Williams Gene: clcnka has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.96 CLCNKA Eleanor Williams Added comment: Comment on mode of inheritance: Digenic recessive with CLCNKB variants.
Renal tubulopathies v1.96 CLCNKA Eleanor Williams Mode of inheritance for gene: CLCNKA was changed from to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.95 CLCN5 Eleanor Williams Mode of inheritance for gene: CLCN5 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)
Renal tubulopathies v1.94 CLCN5 Eleanor Williams Classified gene: CLCN5 as Red List (low evidence)
Renal tubulopathies v1.94 CLCN5 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as Dent disease is covered by the 'R256 Nephrocalcinosis or nephrolithiasis' panel.
Renal tubulopathies v1.94 CLCN5 Eleanor Williams Gene: clcn5 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.93 CASR Eleanor Williams Classified gene: CASR as Green List (high evidence)
Renal tubulopathies v1.93 CASR Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as there are sufficient cases reported in OMIM.
Renal tubulopathies v1.93 CASR Eleanor Williams Gene: casr has been classified as Green List (High Evidence).
Renal tubulopathies v1.92 CASR Eleanor Williams Added comment: Comment on publications: Publications from OMIM
Renal tubulopathies v1.92 CASR Eleanor Williams Publications for gene: CASR were set to
Renal tubulopathies v1.91 CASR Eleanor Williams Mode of inheritance for gene: CASR was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v1.90 ATP1A1 Eleanor Williams Classified gene: ATP1A1 as Green List (high evidence)
Renal tubulopathies v1.90 ATP1A1 Eleanor Williams Added comment: Comment on list classification: Promoting red to green as there are 3 cases plus some functional data.
Renal tubulopathies v1.90 ATP1A1 Eleanor Williams Gene: atp1a1 has been classified as Green List (High Evidence).
Renal tubulopathies v1.89 ATP1A1 Eleanor Williams Phenotypes for gene: ATP1A1 were changed from Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, 618036 to Hypomagnesemia, seizures, and mental retardation 2 618314; Charcot-Marie-Tooth disease, axonal, type 2DD, 618036
Renal tubulopathies v1.88 ATP1A1 Eleanor Williams Mode of inheritance for gene: ATP1A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.87 AP2S1 Eleanor Williams Classified gene: AP2S1 as Green List (high evidence)
Renal tubulopathies v1.87 AP2S1 Eleanor Williams Added comment: Comment on list classification: Sufficient cases to rate green.
Renal tubulopathies v1.87 AP2S1 Eleanor Williams Gene: ap2s1 has been classified as Green List (High Evidence).
Renal tubulopathies v1.86 AP2S1 Eleanor Williams Publications for gene: AP2S1 were set to
Renal tubulopathies v1.85 AP2S1 Eleanor Williams Mode of inheritance for gene: AP2S1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.84 EHHADH Eleanor Williams Classified gene: EHHADH as Amber List (moderate evidence)
Renal tubulopathies v1.84 EHHADH Eleanor Williams Added comment: Comment on list classification: 1 family plus functional data which is sufficient evidence to leave amber.
Renal tubulopathies v1.84 EHHADH Eleanor Williams Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.83 Eleanor Williams List of related panels changed from Renal tubular acidosis to Renal tubular acidosis; R198
Renal tubulopathies v1.82 SCNN1A Eleanor Williams edited their review of gene: SCNN1A: Added comment: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

8 cases reported in OMIM (PMIDs 8589714 and 10586178).; Changed phenotypes: Pseudohypoaldosteronism, type I, MIM 264350, ? Liddle syndrom 3, MIM 618126, Bronchiectasis with or without elevated sweat chloride 2 MIM 613021
Renal tubulopathies v1.82 SCNN1B Eleanor Williams commented on gene: SCNN1B: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

PMID: 8589714 - Chang et al 1996 - report a Arabic kindred from Israel in which a homozygous missense mutation was found in betaENaC (G37S).

PMID: 26807262 - Nobel et al 2016 - report a 32-year-old female with pseudohypoaldosteronism type 1 with persistent, symptomatic hyperkalemia who was compound heterozygous for two variants in SCNN1B (c.1288delC and c.1466+1 G>A). .

PMID: 31301676 - Gopal-Kothandapani et al 2019 - Abstract only accessed - report a patient with PHA1 and a novel mutation in SCNN1B.
Renal tubulopathies v1.82 SCNN1G Eleanor Williams commented on gene: SCNN1G: Associated with Pseudohypoaldosteronism, type I #264350 in OMIM.

OMIM reports that in PMID: 8640238 - Strautnieks et al. 1996 - describe the identification of a 3' splice site mutation in SCNN1G (318-1 G-->A) in three families showing linkage to 16p. These three families all originate from the Indian sub-continent and the probands have severe generalized PHA. They share a common haplotype which suggests the presence of a founder mutation in this sub-population.

PMID: 29582446 - Turan et al 2018 - report a homozygous missense variant (p.A63P) that they classify as a VUS in SCNN1G in a patient (patient 5) with aldosterone defects.
Renal tubulopathies v1.82 SLC22A12 Eleanor Williams commented on gene: SLC22A12: Associated with Hypouricemia, renal #220150 in OMIM.

PMID: 18492088 - Ichida et al 2008 - identified SLC22A12 mutations in 66 of 71 Japanese patients with hypouricemia. A total of 13 mutations, including 3 novel mutations, were identified. Acute renal failure and urolithiasis occurred in 21.1% and 8.5% of patients, respectively.
Renal tubulopathies v1.82 SLC2A9 Eleanor Williams commented on gene: SLC2A9: Associated with Hypouricemia, renal, 2 #612076 in OMIM.

More than 3 cases reported in OMIM (PMIDs: 19026395, 19926891, 21810765). Some patients heterozygous, some homozygous for variants in SLC2A9. In one family the heterozygous parents of the sibs were clinically asymptomatic.
Renal tubulopathies v1.82 SLC34A1 Eleanor Williams edited their review of gene: SLC34A1: Added comment: Associated with ?Fanconi renotubular syndrome 2 #613388, Hypercalcemia, infantile, 2 #616963 and
Nephrolithiasis/osteoporosis, hypophosphatemic, 1 #612286 in OMIM.

Gene also known as NPT2.

PMID: 12324554 - Prie et al 2002 - report 2 out of 20 patients with urolithiasis or osteoporosis and persistent idiopathic hypophosphatemia associated with a decrease in maximal renal phosphate resorption with heterozygous missense mutations in SLC34A1.

PMID: 20335586 - Magen et al 2010 - report an affected brother and sister from a consanguineous Arab family with Fanconi renotubular syndrome and a homozygous in-frame 21-bp duplication in SLC34A1.

PMID: 26047794 - Schlingmann et al 2016 - report biallelic SLC34A1 mutations in 16 patients from 15 families with infantile hypercalcemia-2; Changed phenotypes: Hypercalcemia, infantile, 2, MIM 616963, Nephrolithiasis/osteoporosis, hypophosphatemic, 1, MIM 612286, ?Fanconi renotubular syndrome 2 MIM 613388
Renal tubulopathies v1.82 SLC34A3 Eleanor Williams commented on gene: SLC34A3: Associated with Hypophosphatemic rickets with hypercalciuria #241530 in OMIM.

10 cases reported in OMIM (PMIDs: 16358214, 16358215, 16849419).
Renal tubulopathies v1.82 SLC5A2 Eleanor Williams commented on gene: SLC5A2: Associated with Renal glucosuria #233100 (both AD and AR) in OMIM.

PubMed: 12436245 - van den Heuvel et al. (2002) - 1 case. Turkish patient with congenital isolated renal glucosuria and a homozygous nonsense mutation in exon 11 leading to the formation of a truncated cotransporter. Both parents and a younger brother, all 3 without renal glucosuria, were heterozygous for the mutation.

PubMed: 21165652 - Yu et al. 2011 - screened the SGLT2 (now known as SLC5A2) gene in 4 patients in 4 unrelated Chinese families had persistent glucosuria with no polyuria/polydipsia, and no history of other renal diseases. They identified 5 novel mutations in the probands, including three missense mutations and two splice mutations. All four probands were heterozygous or compound heterozygous for SGLT2 mutations and none of the five identified mutations was detected in 110 chromosomes derived from 55 healthy, unrelated individuals, indicating that these mutations do not represent common polymorphisms. Compound heterozygous patients had more significant glucosuria. Functional studies also carried out.

PubMed: 26376857- Dhayat et al 2016 - report a Swiss family with SLC16A12-associated cataract and microcornea, in which 5 affected individuals also exhibited renal leak glucosuria, They identified an additional heterozygous missense mutation in the SLC5A2 gene that segregated fully with renal leak glucosuria in the family.
Renal tubulopathies v1.82 SLC9A3R1 Eleanor Williams commented on gene: SLC9A3R1: Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 in OMIM.

PubMed: 18784102 - Karim et al 2008 - sequenced the NHERF1 gene (now called SLC9A3R1) in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. They identified three distinct heterozygous missense mutations in the NHERF1 gene in four unrelated patients. All four patients with NHERF1 mutations had TmP/GFR values below the lower limit of the normal range, as well as hypophosphatemia. Patients 1, 3, and 4 also had recurrent nephrolithiasis. The four patients with mutations did not have proximal-tubule dysfunction other than the low TmP/GFR value. The results identify NHERF1 mutations as a cause of renal phosphate loss that may increase the risk of renal stone formation or bone demineralization: the mutations were identified only in patients with TmP/GFR values that were below normal and significantly lower than those in patients in whom mutations were not identified
Renal tubulopathies v1.82 TRPM6 Eleanor Williams commented on gene: TRPM6: Associated with Hypomagnesemia 1, intestinal #602014 in OMIM.

PMID: 12032568 - Schlingmann et al 2002 - 5 families (2 Turkish, 1 Swedish, 1 Israeli, and 1 Albanian) with hypomagnesemia with secondary hypocalcemia and mutations in the TRPM6 gene. In three families the parents were consanguineous and the affected individuals had homozygous variants. In 2 non-consanguineous families the affected children were compound heterozygous for TRPM6 mutations. The age at onset of symptoms varied from 3 weeks to 4 months. Seizures were the first symptoms detected. They also identified TRPM6 expression in kidney, and they report that the individuals studied showed inappropriately high fractional magnesium excretion rates, indicating an additional role of impaired renal magnesium reabsorption in HSH. This is confirmed by the characterisation of a considerable renal leak of magnesium in HSH patients in an accompanying report.

PubMed: 12032570 - Walder et al 2002 - identified homozygous mutations in each of six consanguineous families, and a heterozygous mutation in a nonconsanguineous family with Familial hypomagnesemia with secondary hypocalcemia. The search was narrowed to TPRM6 by homozygosity mapping and then identifying TRPM6 as a likely candidate gene. The gene was then sequenced in each of the families. 3 families were Bedouin kindreds from Israel with the same variant in a splice donor, the other families (each with different variants) were an Arab family from Greece, a family from Germany and 2 Arab families from Israel.

PMID: 23942199 - Lainez et al. 2014 - report from five new missense mutations found in five patients with HSH.
Renal tubulopathies v1.82 UMOD Eleanor Williams commented on gene: UMOD: Associated with Glomerulocystic kidney disease with hyperuricemia and isosthenuria #609886, Hyperuricemic nephropathy, familial juvenile 1 #162000 and Medullary cystic kidney disease 2 #603860 in OMIM.

Many cases reported in OMIM.
Renal tubulopathies v1.82 WNK1 Eleanor Williams commented on gene: WNK1: Associated with Pseudohypoaldosteronism, type IIC (#614492) in OMIM,

PMID: 11498583 - Wilson et al - 2001 - in one large family with 10 members affected by pseudohypoaldosteronism type II they identified a 41-kb deletion in intron 1 of WNK1 that segregated with the disease. In another family previously described by Disse-Nicodeme et al. (2000), they identified a 22-kb deletion within intron 1 of WNK1. Functional studies showed this deletion increased the expression of WNK1.
Renal tubulopathies v1.82 WNK4 Eleanor Williams commented on gene: WNK4: Associated with Pseudohypoaldosteronism, type IIB #614491 in OMIM.

PMID: 11498583 - Wilson et al. 2001 - Examination of WNK4 in PHAII kindreds identified four missense mutations, all of
which cosegregated with the disease.Three of these are charge-changing substitutions that cluster in a span of four amino acids within a negatively charged 10-amino acid segment that is highly conserved among all members of the WNK family in human as well as orthologs in mouse and rat
Renal tubulopathies v1.82 REN Eleanor Williams changed review comment from: Associated with Hyperuricemic nephropathy, familial juvenile 2 #613092 (AD) and Renal tubular dysgenesis #267430 (AR) in OMIM.

PMID: 16116425 - Gribouval et al 2005 - abstract only accessed. They studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. From the abstract cannot tell how many families had mutations in renin but the review of Gribouval et al 2012 (PMID: 22095942) - lists 12 different variants in REN as causing Renal Tublular Dysgenesis, including those reported in the Gribouval et al 2005 paper and the 2012 report, and other publications Michaud et al. [2011](PMID: 21036942), Bacchetta et al. [2007](PMID: 17555949).

PMID: 19664745 - Zivna et al 2009 - identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin.; to: Associated with Hyperuricemic nephropathy, familial juvenile 2 #613092 (AD) and Renal tubular dysgenesis #267430 (AR) in OMIM.

Gribouval et al 2012 (PMID: 22095942) - lists 12 different variants in REN as causing Renal Tublular Dysgenesis, including those reported in this study and Gribouval et al 2005 (PMID: 16116425), Michaud et al. [2011](PMID: 21036942) and Bacchetta et al. [2007](PMID: 17555949).

PMID: 19664745 - Zivna et al 2009 - identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin.
Renal tubulopathies v1.82 REN Eleanor Williams commented on gene: REN: Associated with Hyperuricemic nephropathy, familial juvenile 2 #613092 (AD) and Renal tubular dysgenesis #267430 (AR) in OMIM.

PMID: 16116425 - Gribouval et al 2005 - abstract only accessed. They studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. From the abstract cannot tell how many families had mutations in renin but the review of Gribouval et al 2012 (PMID: 22095942) - lists 12 different variants in REN as causing Renal Tublular Dysgenesis, including those reported in the Gribouval et al 2005 paper and the 2012 report, and other publications Michaud et al. [2011](PMID: 21036942), Bacchetta et al. [2007](PMID: 17555949).

PMID: 19664745 - Zivna et al 2009 - identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin.
Renal tubulopathies v1.82 OCRL Eleanor Williams commented on gene: OCRL: Associated with Dent disease 2 #300555 and Lowe syndrome #309000 in OMIM both with reported renal clinical features.

Many cases of association between variants in OCRL and these diseases reported in OMIM.
e.g. PMID: 10364518 (Satre et al 1999) reports on 8 famlies with Lowe Syndrome. Five of these eight pedigrees had a family history of at least two male patients carrying a clinical diagnosis of Lowe syndrome on the basis of the classic triad of defects affecting lens, brain and kidney. Seven new mutations and one recurrent mutation were identified in the OCRL1 gene in one carrier mother and in seven affected patients. They identified a germ-line mosaicism in one family.
Renal tubulopathies v1.82 NR3C2 Eleanor Williams commented on gene: NR3C2: Associated with Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy #605115 and
Pseudohypoaldosteronism type I, autosomal dominant #177735 in OMIM.

The gene is also known as MCR.
Many cases of Pseudohypoaldosteronism associated with variants in NR3C2 reported in OMIM.
Renal tubulopathies v1.82 MAGED2 Eleanor Williams commented on gene: MAGED2: Associated with Bartter syndrome, type 5, antenatal, transient #300971 in OMIM.

Laghmani et al. (2016) - identified variants in MAGED2 in 13 infants from 9 families who had transient antenatal Bartter's syndrome. All affected infants were male. They observed prominent tubular expression of MAGE-D2 in the human fetal renal cortex. In total, seven truncating mutations (two nonsense, two frameshift, and three splice-site mutations) and two nontruncating mutations (one missense and one in-frame deletion) were identified.
Renal tubulopathies v1.82 KLHL3 Eleanor Williams commented on gene: KLHL3: Associated with Pseudohypoaldosteronism, type IID 614495 in OMIM.
Many reports of cases in OMIM. Both monoallelic and biallelic.
Renal tubulopathies v1.82 KCNJ10 Eleanor Williams commented on gene: KCNJ10: Associated with SESAME syndrome #612780 in OMIM which includes a renal phenotype.

Many cases (> 3) reported in OMIM.
Renal tubulopathies v1.82 HNF1B Eleanor Williams commented on gene: HNF1B: Associated with Renal cysts and diabetes syndrome #137920 in OMIM.

Many cases reported in OMIM of cases with variants in HNF1B and Renal cysts and diabetes syndrome.
Renal tubulopathies v1.82 GNAS Eleanor Williams commented on gene: GNAS: Linked to several disease phenotypes in OMIM but they don't appear relevant to a renal disease.

PMID: 30312418 Biebermann et al 2018 - two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function. Both unrelated patients presented severe asymptomatic infantile hyponatremia, skeletal and growth plate abnormalities, early onset pubertal development, and apparent PTH resistance in the proximal but not in the distal renal tubules. An identical heterozygous de novo variant (c.1136T>G; p.F376V) was found on the maternal GNAS allele in both patients.
Renal tubulopathies v1.82 GNA11 Eleanor Williams commented on gene: GNA11: Associated with Hypocalcemia, autosomal dominant 2 #615361 and Hypocalciuric hypercalcemia, type II #145981 in OMIM.

PMID: 23802536 - Mannstadt et al 2013 - in 2 unrelated 4-generation families with segregating autosomal dominant hypocalcemia they identified heterozygous missense mutations (c.178C-T, R60C and c.632C-G , S211W) that segregated with disease in each family. **However, none of the affected members in either family had a history of renal abnormalities.**

PMID: 24823460 - Li et al 2014 - ina large 4-generation family segregating autosomal dominant hypocalcemia/autosomal dominant hypoparathyroidism and short stature, they identified a heterozygous missense mutation in the GNA11 gene (R60L) that segregated with disease in the family. The initial proband identified had nephrogenic diabetes insipidus along with short stature.The basis for this episode of transient diabetes insipidus remains unknown, and no other member of the extended family has ever manifested symptoms of diabetes insipidus.
Renal tubulopathies v1.82 GATM Eleanor Williams commented on gene: GATM: PMID: 29654216 (Reichold et al 2018) reports 5 families with with a novel form of autosomal dominant kidney disease characterized by renal tubular Fanconi syndrome early in life followed by progression to renal glomerular failure in mid-adulthood. All patients show monoallelic mutations in the gene GATM. 4 heterozygous missense mutations of evolutionary conserved amino acid residues in GATM were found (c.958C>T, p.P320S; c.1006A>G, p.T336A; c.1007C>T, p.T336I;
c.1022C>T, p.P341L). In each family, one variant segregated with the disorder and was fully penetrant. In silico analysis showed that the particular GATM mutations create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells.
Renal tubulopathies v1.82 FXYD2 Eleanor Williams commented on gene: FXYD2: Associated with Hypomagnesemia 2, renal #154020 in OMIM.


PMID: 11062458 - Meij et al 2000 - Identified a heterozygous mutation, 123G→A in FXYD2 in a large Dutch family with dominant hypomagnesaemia which cosegregated with the disorder. The mutation causes the substitution of the conserved glycine 41 within the putative transmembrane domain by arginine.

PMID: 2576584 - de Baaij et al 2015 - two families (Dutch and Belgian) with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. The same mutation as reported before was found in these families, c.115G>A, p.Gly41Arg, and haplotype analysis revealed an overlapping haplotype in all families, suggesting a founder effect.

3 cases but likely linked by common ancestor as same variant found in all three.
Renal tubulopathies v1.82 CYP24A1 Eleanor Williams commented on gene: CYP24A1: Associated with Hypercalcemia, infantile, 1 143880 in OMIM.

PMID: 21675912 - Schlingmann et al 2011 - from OMIM - In 7 patients from 8 unrelated families with infantile hypercalcemia-1 they identified homozygosity or compound heterozygosity for mutations in the CYP24A1 gene. In 1 patient, a heterozygous complex deletion in CYP24A1 was identified, but no other mutation was detected by sequence analysis.

PMID: 22047572 - Streeten et al 2011 - from OMIM- 47-year-old man who had an episode of nephrolithiasis at 19 years of age and was subsequently asymptomatic until hypercalcemia was discovered on routine testing at 39 years of age, Streeten et al. identified homozygosity for a 3-bp deletion in the CYP24A1 gene.
Renal tubulopathies v1.82 CUL3 Eleanor Williams commented on gene: CUL3: Associated with Pseudohypoaldosteronism, type IIE 614496 in OMIM

PMID: 22266938 - Boyden et al 2012 - used exome sequencing to study a cohort of 52 PHAII kindreds, including 126 affected subjects with renal hyperkalemia. They identified seventeen with novel heterozygous mutations, all in cases without KLHL3, WNK1 or WNK4 mutations. Eight of these mutations were documented to be de novo.
Renal tubulopathies v1.82 CLDN19 Eleanor Williams commented on gene: CLDN19: Associated with Hypomagnesemia 5, renal, with ocular involvement 248190 in OMIM.

Many cases reported in OMIM.
Renal tubulopathies v1.82 CLDN16 Eleanor Williams commented on gene: CLDN16: Associated with Hypomagnesemia 3, renal 248250 in OMIM.
Previous gene symbol of PCLN1.

Many cases reported in OMIM.
Renal tubulopathies v1.82 CLDN10 Eleanor Williams changed review comment from: Associated with HELIX syndrome 617671 in OMIM. This disorder is characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis.

PMID: 28674042 - Bongers et al 2017 - characterized CLDN10 mutations in two unrelated patients with a hypokalemic-alkalotic salt-losing nephropathy. In both compound heterozygous variants were found [c.446C>G (p.Pro149Arg) and c.465-1G>A (p.Glu157_Tyr192del)] and [c.446C>G (p.(Pro149Arg) and c.217G>A (p.Asp73Asn)]. Variants segregated with the disorder in both families. The identified CLDN10 sequence variants were not reported in the Exome Aggregation Consortium database.

PMID: 19307729 - paper unrelated to CLDN10; to: Associated with HELIX syndrome 617671 in OMIM. This disorder is characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis. 3 cases reported in OMIM.

PMID: 28674042 - Bongers et al 2017 - characterized CLDN10 mutations in two unrelated patients with a hypokalemic-alkalotic salt-losing nephropathy. In both compound heterozygous variants were found [c.446C>G (p.Pro149Arg) and c.465-1G>A (p.Glu157_Tyr192del)] and [c.446C>G (p.(Pro149Arg) and c.217G>A (p.Asp73Asn)]. Variants segregated with the disorder in both families. The identified CLDN10 sequence variants were not reported in the Exome Aggregation Consortium database.

PMID: 19307729 - paper unrelated to CLDN10
Renal tubulopathies v1.82 CLDN10 Eleanor Williams edited their review of gene: CLDN10: Added comment: Associated with HELIX syndrome 617671 in OMIM. This disorder is characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis.

PMID: 28674042 - Bongers et al 2017 - characterized CLDN10 mutations in two unrelated patients with a hypokalemic-alkalotic salt-losing nephropathy. In both compound heterozygous variants were found [c.446C>G (p.Pro149Arg) and c.465-1G>A (p.Glu157_Tyr192del)] and [c.446C>G (p.(Pro149Arg) and c.217G>A (p.Asp73Asn)]. Variants segregated with the disorder in both families. The identified CLDN10 sequence variants were not reported in the Exome Aggregation Consortium database.

PMID: 19307729 - paper unrelated to CLDN10; Changed phenotypes: Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number), HELIX syndrome, MIM 617671
Renal tubulopathies v1.82 CLCNKA Eleanor Williams commented on gene: CLCNKA: Associated with Bartter syndrome, type 4b, digenic (#613090) in OMIM.

PMID: 15044642 - Schlingmann et al 2004 - in a child with a child with renal salt wasting and deafness, they identified both a homozygous deletion of the CLCNKB gene and a homozygous trp80-to-cys mutation in the CLCNKA gene (W80C).

Nozu et al 2008 - 2-year-old Japanese girl with a severe form of Bartter syndrome with sensorineural deafness. Parents were nonconsanguineous. They found 2 heterozygous mutations in the CLCNKA and CLCNKB genes on the paternal allele, and a 12-kb deletion involving portions of the CLCNKA and CLCNKB genes on the maternal allele. Neither parent was clinically affected.
Renal tubulopathies v1.82 CLCN5 Eleanor Williams commented on gene: CLCN5: Associated with Dent disease (#300009), Hypophosphatemic rickets (#300554), Nephrolithiasis, type I (#310468) and Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis (#308990) in OMIM.

Many cases reported in OMIM.
Renal tubulopathies v1.82 CASR Eleanor Williams commented on gene: CASR: Associated with Hyperparathyroidism, neonatal (#239200), Hypocalcemia, autosomal dominant (#601198), Hypocalcemia, autosomal dominant, with Bartter syndrome (#601198) and Hypocalciuric hypercalcemia, type I (#145980) in OMIM.

Many cases reported in OMIM.
Renal tubulopathies v1.82 ATP1A1 Eleanor Williams commented on gene: ATP1A1: Associated with Hypomagnesemia, seizures, and mental retardation 2 (#618314) in OMIM.

PMID: 30388404 - Schlingmann et al 2018 - describe 3 unrelated infants who are from non-consanguineous families and who presented with a disease phenotype consisting of generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Whole-exome sequencing and conventional Sanger sequencing identified heterozygous de novo mutations in ATP1A1 (p.Leu302Arg, p.Gly303Arg, p.Met859Arg). Functional studies show the critical role of the α1 subunit of Na+, K+-ATPase for the maintenance of ionic gradients, the generation of resting membrane potential, and the termination of neuronal activity in the central nervous system
Renal tubulopathies v1.82 AP2S1 Eleanor Williams commented on gene: AP2S1: Associated with Hypocalciuric hypercalcemia, type III (#600740) in OMIM.

PMID: 23222959 - Nesbit et al 2013 - in 2 unrelated 3-generation families segregating autosomal dominant hypocalciuric hypercalcemia they identified a heterozygous missense mutation in the AP2S1 gene (R15C). DNA sequence analysis of the 5 exons and 8 intron-exon boundaries of AP2S1 of a further 50 unrelated patients in whom CaSR mutations had been excluded, found a further 11 probands from 10 families, with missense heterozygous mutations, consistent with autosomal dominant inheritance of familial hypocalciuric hypercalcemia type 3, that all affected Arg15.
Renal tubulopathies v1.81 GATM Eleanor Williams Phenotypes for gene: GATM were changed from to Renal fanconi syndrome and kidney failure (no MIM number); Cerebral creatine deficiency syndrome 3, 612718 (AR)
Renal tubulopathies v1.80 GATM Eleanor Williams Publications for gene: GATM were set to
Renal tubulopathies v1.79 GNAS Eleanor Williams Phenotypes for gene: GNAS were changed from to Unexplained hyponatremia in infancy, severe early-onset gonadotrophin-independent precocious puberty and skeletal abnormalities.
Renal tubulopathies v1.78 GNAS Eleanor Williams Publications for gene: GNAS were set to
Renal tubulopathies v1.77 MAGED2 Eleanor Williams Phenotypes for gene: MAGED2 were changed from to Bartter syndrome, type 5, antenatal, transient, 300971
Renal tubulopathies v1.76 MAGED2 Eleanor Williams Publications for gene: MAGED2 were set to
Renal tubulopathies v1.75 FOXI1 Eleanor Williams Phenotypes for gene: FOXI1 were changed from deafness; renal tubular acidosis to deafness; renal tubular acidosis; Early onset sensorinerual deafness and distal renal tubular acidosis (no OMIM number); Enlarged vestibular aqueducts, 6007910
Renal tubulopathies v1.74 ATP1A1 Eleanor Williams Phenotypes for gene: ATP1A1 were changed from to Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number); Charcot-Marie-Tooth disease, axonal, type 2DD, 618036
Renal tubulopathies v1.73 ATP1A1 Eleanor Williams Publications for gene: ATP1A1 were set to
Renal tubulopathies v1.72 CLDN10 Eleanor Williams Phenotypes for gene: CLDN10 were changed from to Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number); HELIX syndrome, 617671
Renal tubulopathies v1.71 CLDN10 Eleanor Williams Publications for gene: CLDN10 were set to
Renal tubulopathies v1.70 WNK4 Eleanor Williams Phenotypes for gene: WNK4 were changed from to Pseudohypoaldosteronism, type IIB, 614491
Renal tubulopathies v1.69 WNK1 Eleanor Williams Phenotypes for gene: WNK1 were changed from to Pseudohypoaldosteronism, type IIC, 614492; Neuropathy, hereditary sensory and autonomic, type II, 201300 (AR)
Renal tubulopathies v1.68 UMOD Eleanor Williams Phenotypes for gene: UMOD were changed from to Hyperuricemic nephropathy, familial juvenile 1, 162000; Glomerulocystic kidney disease with hyperuricemia and isosthenuria, 609886; Medullary cystic kidney disease 2, 603860
Renal tubulopathies v1.67 TRPM6 Eleanor Williams Phenotypes for gene: TRPM6 were changed from 602014 to Hypomagnesemia 1, intestinal, 602014
Renal tubulopathies v1.66 SLC9A3R1 Eleanor Williams Phenotypes for gene: SLC9A3R1 were changed from to Nephrolithiasis/osteoporosis, hypophosphatemic, 2, 612287
Renal tubulopathies v1.65 SLC5A2 Eleanor Williams Phenotypes for gene: SLC5A2 were changed from to Renal glucosuria, 233100
Renal tubulopathies v1.64 SLC4A1 Eleanor Williams Phenotypes for gene: SLC4A1 were changed from Distal Renal Tubular Acidosis, Dominant; Ovalocytosis; Distal renal tubular acidosis to Distal Renal Tubular Acidosis, Dominant; Ovalocytosis; Distal renal tubular acidosis; Renal tubular acidosis, distal, AD,179800; Renal tubular acidosis, distal, AR, 611590; Cryohydrocytosis, 185020; Ovalocystois, SA type 166900; Spherocytoisis type 4, 612653; various blood group associations.
Renal tubulopathies v1.63 SLC4A1 Eleanor Williams Publications for gene: SLC4A1 were set to
Renal tubulopathies v1.62 SLC34A3 Eleanor Williams Phenotypes for gene: SLC34A3 were changed from to Hypophosphatemic rickets with hypercalciuria, 241530
Renal tubulopathies v1.61 SLC34A1 Eleanor Williams Phenotypes for gene: SLC34A1 were changed from to Hypercalcemia, infantile, 2, MIM 616963; Nephrolithiasis/osteoporosis, hypophosphatemic, 1, 612286; ?Fanconi renotubular syndrome 2 613388
Renal tubulopathies v1.60 SLC2A9 Eleanor Williams Phenotypes for gene: SLC2A9 were changed from to Hypouricemia, renal, 2, 612076; {Uric acid concentration, serum, QTL 2}, 612076
Renal tubulopathies v1.59 SLC22A12 Eleanor Williams Phenotypes for gene: SLC22A12 were changed from to Hypouricemia, renal, 220150
Renal tubulopathies v1.58 SLC12A3 Eleanor Williams Phenotypes for gene: SLC12A3 were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria to Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Gitelman syndrome, 263800
Renal tubulopathies v1.57 SLC12A1 Eleanor Williams Phenotypes for gene: SLC12A1 were changed from Type 1 Bartter syndrome: infantile onset, pregnancy noted for polyhydramnios. Hyperprostagladinuria. Hypokalaemia and metabolic alkalosis +/- nephrocalcinosis. to Type 1 Bartter syndrome: infantile onset, pregnancy noted for polyhydramnios. Hyperprostagladinuria. Hypokalaemia and metabolic alkalosis +/- nephrocalcinosis; Bartter syndrome, type 1, 601678
Renal tubulopathies v1.56 SCNN1G Eleanor Williams Phenotypes for gene: SCNN1G were changed from to Pseudohypoaldosteronism, type I, 264350
Renal tubulopathies v1.55 SCNN1B Eleanor Williams Phenotypes for gene: SCNN1B were changed from genes for Liddle, GRA, PHA1, hypomagnesemia without stones, AME are all missing to genes for Liddle, GRA, PHA1, hypomagnesemia without stones, AME are all missing; Pseudohypoaldosteronism, type I, 264350
Renal tubulopathies v1.54 SCNN1A Eleanor Williams Phenotypes for gene: SCNN1A were changed from to Pseudohypoaldosteronism, type I, 264350; ?Liddle syndrom 3, 618126; Bronchiectasis with or without elevated sweat chloride 2 613021
Renal tubulopathies v1.53 REN Eleanor Williams Phenotypes for gene: REN were changed from to Hyperuricemic nephropathy, familial juvenile 2, 613092; Renal tubular dysgenesis 267430 AR
Renal tubulopathies v1.52 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from to Dent disease 2, 300555. Lowe syndrome, 309000
Renal tubulopathies v1.51 NR3C2 Eleanor Williams Phenotypes for gene: NR3C2 were changed from to Pseudohypoaldosteronism type I, autosomal dominant, 177735; Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy, 605115 no inheritance pattern
Renal tubulopathies v1.50 KLHL3 Eleanor Williams Phenotypes for gene: KLHL3 were changed from to Pseudohypoaldosteronism, type IID, 614495
Renal tubulopathies v1.49 KCNJ10 Eleanor Williams Phenotypes for gene: KCNJ10 were changed from to SESAME/EAST syndrome, 612780; Enlarged vestibular aqueduct, digenic, 60079
Renal tubulopathies v1.48 KCNJ1 Eleanor Williams Phenotypes for gene: KCNJ1 were changed from Hypokalaemic alkalosis with hypercalciuria; Type 2 Bartter syndrome; often initial transient hyperkalemia to Hypokalaemic alkalosis with hypercalciuria; Type 2 Bartter syndrome; often initial transient hyperkalemia; Bartter syndrome, type 2, 241200
Renal tubulopathies v1.47 KCNA1 Eleanor Williams Phenotypes for gene: KCNA1 were changed from to Autosomal dominant hypomagnesemia; Episodic ataxia/myokymia syndrome,160120
Renal tubulopathies v1.46 KCNA1 Eleanor Williams Publications for gene: KCNA1 were set to
Renal tubulopathies v1.45 HNF1B Eleanor Williams Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, 137920; Diabetes mellitus, noninsulin-dependent, 125853
Renal tubulopathies v1.44 GNA11 Eleanor Williams Phenotypes for gene: GNA11 were changed from to Hypocalcemia, autosomal dominant 2 615361
Renal tubulopathies v1.43 FXYD2 Eleanor Williams Phenotypes for gene: FXYD2 were changed from to Hypomagnesemia 2, renal, 154020
Renal tubulopathies v1.42 EHHADH Eleanor Williams Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615
Renal tubulopathies v1.41 EGF Eleanor Williams Phenotypes for gene: EGF were changed from to Hypomagnesemia 4, renal, 611718
Renal tubulopathies v1.40 EGF Eleanor Williams Publications for gene: EGF were set to
Renal tubulopathies v1.39 CYP24A1 Eleanor Williams Phenotypes for gene: CYP24A1 were changed from to Hypercalcemia, infantile, 1 143880
Renal tubulopathies v1.38 CUL3 Eleanor Williams Phenotypes for gene: CUL3 were changed from to Pseudohypoaldosteronism, type IIE, 214496
Renal tubulopathies v1.37 CTNS Eleanor Williams Phenotypes for gene: CTNS were changed from Cystinosis, atypical nephropathic 219800; Cystinosis, late-onset juvenile or adolescent nephropathic 219900; Cystinosis, nephropathic 219800 to Cystinosis, atypical nephropathic 219800; Cystinosis, late-onset juvenile or adolescent nephropathic 219900; Cystinosis, nephropathic 219800; Cystinosis, ocular nonnephropathic 219750
Renal tubulopathies v1.36 CLDN19 Eleanor Williams Phenotypes for gene: CLDN19 were changed from to Hypomagnesemia 5, renal, with ocular involvement, 248190
Renal tubulopathies v1.35 CLDN16 Eleanor Williams Phenotypes for gene: CLDN16 were changed from to Hypomagnesemia 3, renal 248250
Renal tubulopathies v1.34 CLCNKB Eleanor Williams Phenotypes for gene: CLCNKB were changed from Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria to Hypokalaemic alkalosis with hypomagnesaemia & hypocalciuria; Bartter syndrome, type 3, 607394
Renal tubulopathies v1.33 CLCNKA Eleanor Williams Phenotypes for gene: CLCNKA were changed from to Bartter syndrome, type 4b, digenic 613090
Renal tubulopathies v1.32 CLCNKA Eleanor Williams Publications for gene: CLCNKA were set to
Renal tubulopathies v1.31 CLCN5 Eleanor Williams Phenotypes for gene: CLCN5 were changed from Dent disease, MIM 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990 to Dent disease, 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990
Renal tubulopathies v1.30 CLCN5 Eleanor Williams Phenotypes for gene: CLCN5 were changed from to Dent disease, MIM 300009. Hypophosphatemic rickets, 300554. Nephrolithiasis, type I, 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, 308990
Renal tubulopathies v1.29 CASR Eleanor Williams Phenotypes for gene: CASR were changed from to Hypocalcemia, autosomal dominant, (with Bartter syndrome), 601198; Hypocalciuric hypercalcemia, type I, 145980; Hyperparathyroidism, neonatal, 239200
Renal tubulopathies v1.28 AVPR2 Eleanor Williams Phenotypes for gene: AVPR2 were changed from Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation) to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation); Nephrogenic syndrome of inappropriate antidiuresis, 300539
Renal tubulopathies v1.27 ATP6V0A4 Eleanor Williams Phenotypes for gene: ATP6V0A4 were changed from Distal Renal Tubular Acidosis, Recessive; Renal tubular acidosis, distal, autosomal recessive, 602722; Distal renal tubular acidosis to Distal Renal Tubular Acidosis, Recessive; Renal tubular acidosis, distal, autosomal recessive, 602722; Distal renal tubular acidosis; Autosomal recessive distal renal tubular acidosis
Renal tubulopathies v1.26 AQP2 Eleanor Williams Phenotypes for gene: AQP2 were changed from Diabetes insipidus, nephrogenic, 125800 to Diabetes insipidus, nephrogenic, 125800; Nephrogenic diabetes insipidus
Renal tubulopathies v1.25 AP2S1 Eleanor Williams Phenotypes for gene: AP2S1 were changed from to Familial hypocalciuric hypercalcemia type III 600740
Renal tubulopathies v1.24 ABCG2 Eleanor Williams Phenotypes for gene: ABCG2 were changed from to Serum uric acid concentration and susceptibility to gout, 138900
Renal tubulopathies v1.23 ABCG2 Eleanor Williams Mode of inheritance for gene: ABCG2 was changed from to Unknown
Renal tubulopathies v1.22 BSND Eleanor Williams Phenotypes for gene: BSND were changed from Hypokalaemic alkalosis with hypercalciuria to Hypokalaemic alkalosis with hypercalciuria; Bartter syndrome type 4a; Sensorineural deafness with mild renal dysfunction MIM 602522
Renal tubulopathies v1.21 EHHADH Anna de Burca Classified gene: EHHADH as Amber List (moderate evidence)
Renal tubulopathies v1.21 EHHADH Anna de Burca Added comment: Comment on list classification: Single family reported with additional functional data. Gene demoted to amber pending further evidence for re-evaluation.
Renal tubulopathies v1.21 EHHADH Anna de Burca Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.20 WDR72 Eleanor Williams Phenotypes for gene: WDR72 were changed from distal RTA to distal RTA; hereditary distal renal tubular acidosis
Renal tubulopathies v1.19 WDR72 Eleanor Williams Classified gene: WDR72 as Amber List (moderate evidence)
Renal tubulopathies v1.19 WDR72 Eleanor Williams Added comment: Comment on list classification: Rating this gene as amber as 2 reported families to date.
Renal tubulopathies v1.19 WDR72 Eleanor Williams Gene: wdr72 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.18 WDR72 Eleanor Williams commented on gene: WDR72
Renal tubulopathies v1.18 EHHADH Eleanor Williams Publications for gene: EHHADH were set to 24401050
Renal tubulopathies v1.17 EHHADH Eleanor Williams commented on gene: EHHADH: PMID: 24401050 (Klootwijk et al 2014) - five-generation black family with isolated autosomal dominant Fanconi's syndrome. They found a heterozygous missense (p.E3K) mutation in EHHADH segregated with the disease. It results in a new mitochondrial targeting motif in the N-terminal portion of EHHADH. Functional studies of proximal tubular cells revealed impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids and a glucose analogue across the epithelium.
Renal tubulopathies v1.17 EHHADH Eleanor Williams Publications for gene: EHHADH were set to
Renal tubulopathies v1.16 GATM Eleanor Williams reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: Reichold et al 2018 J Am Soc Nephrol 29(7): 1849-1858. PMID: 29654216; Phenotypes: Renal fanconi syndrome and kidney failure (no MIM number), Cerebral creatine deficiency syndrome 3, MIM 612718 (AR); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.16 GNAS Eleanor Williams reviewed gene: GNAS: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: Biebermann et al 2018 PMID: 30312418; Phenotypes: Unexplained hyponatremia in infancy, severe early-onset gonadotrophin-independent precocious puberty and skeletal abnormalities.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed); Current diagnostic: yes
Renal tubulopathies v1.16 MAGED2 Eleanor Williams reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: ; Publications: Laghmani et al 2016 N Eng J Med 374: 1853-1863. PMID: 27120771; Phenotypes: Bartter syndrome, type 5, antenatal, transient, MIM 300971; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal tubulopathies v1.16 FOXI1 Eleanor Williams reviewed gene: FOXI1: Rating: AMBER; Mode of pathogenicity: ; Publications: Enerback et al 2018 J Am Soc Nephrol 29 (3): 1041-1048. PMID: 29242249; Phenotypes: Early onset sensorinerual deafness and distal renal tubular acidosis (no OMIM number), Enlarged vestibular aqueducts, MIM 6007910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.16 ATP1A1 Eleanor Williams reviewed gene: ATP1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: Schlingmann et al 2018 Am J Hum Genet 103 (5) 808-816. PMID: 30388404; Phenotypes: Renal hypomagnesemia, refractory seizures and intellectual disability (no OMIM number), Charcot-Marie-Tooth disease, axonal, type 2DD, MIM 618036; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal tubulopathies v1.16 CLDN10 Eleanor Williams reviewed gene: CLDN10: Rating: AMBER; Mode of pathogenicity: ; Publications: Bongers et al 2017 J Am Soc Nephrol 28 (10): 3118-3128. PMID 19307729; Phenotypes: Hypokalemic-alkalotic salt-losing tubulopathy (no OMIM number), HELIX syndrome, MIM 617671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.16 WNK4 Eleanor Williams reviewed gene: WNK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type IIB, MIM 614491; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 WNK1 Eleanor Williams reviewed gene: WNK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type IIC, MIM 614492, Neuropathy, hereditary sensory and autonomic, type II, MIM 201300 (AR); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 UMOD Eleanor Williams reviewed gene: UMOD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperuricemic nephropathy, familial juvenile 1, MIM 162000, Glomerulocystic kidney disease with hyperuricemia and isosthenuria, MIM 609886, Medullary cystic kidney disease 2, MIM 603860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 TRPM6 Eleanor Williams reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomagnesemia 1, intestinal, MIM 602014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC9A3R1 Eleanor Williams reviewed gene: SLC9A3R1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM 612287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 SLC5A2 Eleanor Williams reviewed gene: SLC5A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal glucosuria, MIM 233100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC4A4 Eleanor Williams reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM 604278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC4A1 Eleanor Williams reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal tubular acidosis, distal, AD, MIM 179800, Renal tubular acidosis, distal, AR, MIM 611590, Cryohydrocytosis, MIM 185020, Ovalocystois, SA type MIM 166900, Spherocytoisis type 4, MIM 612653, various blood group associations.; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC34A3 Eleanor Williams reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets with hypercalciuria, MM 241530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC34A1 Eleanor Williams reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypercalcemia, infantile, 2, MIM 616963, Nephrolithiasis/osteoporosis, hypophosphatemic, 1, MIM 612286, ?Fanconi renotubular syndrome 2 MIM 613388; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC2A9 Eleanor Williams reviewed gene: SLC2A9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypouricemia, renal, 2, MIM 612076, {Uric acid concentration, serum, QTL 2} MIM 612076; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC22A12 Eleanor Williams reviewed gene: SLC22A12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypouricemia, renal, MIM 220150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC12A3 Eleanor Williams reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Gitelman syndrome, MIM 263800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SLC12A1 Eleanor Williams reviewed gene: SLC12A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bartter syndrome, type 1, MIM 601678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SCNN1G Eleanor Williams reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM 264350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SCNN1B Eleanor Williams reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM 264350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 SCNN1A Eleanor Williams reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type I, MIM 264350, ? Liddle syndrom 3, MIM 618126, Bronchiectasis with or without elevated sweat chloride 2 MIM 613021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 REN Eleanor Williams reviewed gene: REN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hyperuricemic nephropathy, familial juvenile 2, MIM 613092, Also Renal tubular dysgenesis MIM 267430 AR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 OCRL Eleanor Williams reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dent disease 2, MIM 300555. Lowe syndrome, MIM 309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Renal tubulopathies v1.16 NR3C2 Eleanor Williams reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism type I, autosomal dominant, MIM 177735, Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy MIM 605115 no inheritance pattern; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 KLHL3 Eleanor Williams reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type IID, MIM 614495; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 KCNJ10 Eleanor Williams reviewed gene: KCNJ10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SESAME/EAST syndrome, MIM 612780, Enlarged vestibular aqueduct, digenic, MIM 600791; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 KCNJ1 Eleanor Williams reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bartter syndrome, type 2, MIM 241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 KCNA1 Eleanor Williams reviewed gene: KCNA1: Rating: RED; Mode of pathogenicity: ; Publications: Glaudemans et al J Clin Invest.2009 Apr 119(4):936-42. PMID 19307729 ; Phenotypes: Autosomal dominant hypomagnesemia (no MIM #), Episodic ataxia/myokymia syndrome MIM 160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 HNF1B Eleanor Williams reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal cysts and diabetes syndrome, MIM 137920, Diabetes mellitus, noninsulin-dependent, MIM 125853; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 GNA11 Eleanor Williams reviewed gene: GNA11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypocalcemia, autosomal dominant 2 MIM 615361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 FXYD2 Eleanor Williams reviewed gene: FXYD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomagnesemia 2, renal MIM 154020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 EHHADH Eleanor Williams reviewed gene: EHHADH: Rating: RED; Mode of pathogenicity: ; Publications: Klootwijk et al New Eng. J. Med. 370: 129-138, 2014. PubMed: 24401050; Phenotypes: ?Fanconi renotubular syndrome 3 MIM 605615; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 EGF Eleanor Williams reviewed gene: EGF: Rating: RED; Mode of pathogenicity: ; Publications: Groenestege et al J. Clin. Invest. 117: 2260-2267, 2007. PubMed: 17671655; Phenotypes: Hypomagnesemia 4, renal, MIM 611718.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CYP24A1 Eleanor Williams reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypercalcemia, infantile, 1 MIM 143880; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CUL3 Eleanor Williams reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Pseudohypoaldosteronism, type IIE, MIM 214496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 CTNS Eleanor Williams reviewed gene: CTNS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cystinosis, nephropathic MIM 219800. Cystinosis, ocular nonnephropathic MIM 219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CLDN19 Eleanor Williams reviewed gene: CLDN19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomagnesemia 5, renal, with ocular involvement, MIM 248190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CLDN16 Eleanor Williams reviewed gene: CLDN16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomagnesemia 3, renal MIM 248250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CLCNKB Eleanor Williams reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bartter syndrome, type 3, MIM 607394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CLCNKA Eleanor Williams reviewed gene: CLCNKA: Rating: AMBER; Mode of pathogenicity: ; Publications: Nozu et al J. Med. Genet. 45: 182-186, 2008. PubMed: 18310267; Phenotypes: Bartter syndrome, type 4b, digenic MIM 613090; Mode of inheritance: Unknown; Current diagnostic: yes
Renal tubulopathies v1.16 CLCN5 Eleanor Williams reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dent disease, MIM 300009. Hypophosphatemic rickets, MIM 300554. Nephrolithiasis, type I, MIM 310468. Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, MIM 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
Renal tubulopathies v1.16 CASR Eleanor Williams reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypocalcemia, autosomal dominant, (with Bartter syndrome) MIM 601198, Hypocalciuric hypercalcemia, type I MIM 145980, Hyperparathyroidism, neonatal MIM 239200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 CA2 Eleanor Williams reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis MIM 259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 BSND Eleanor Williams reviewed gene: BSND: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Bartter syndrome type 4a, Sensorineural deafness with mild renal dysfunction MIM 602522; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 AVPR2 Eleanor Williams reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: ; Phenotypes: Nephrogenic diabetes insipidus MIM 304800, Nephrogenic syndrome of inappropriate antidiuresis MIM 300539; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Renal tubulopathies v1.16 ATP6V1B1 Eleanor Williams reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Renal tubular acidosis with deafness MIM 267300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 ATP6V0A4 Eleanor Williams reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Autosomal recessive distal renal tubular acidosis MIM 602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 AQP2 Eleanor Williams reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephrogenic diabetes insipidus, MIM 125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Renal tubulopathies v1.16 AP2S1 Eleanor Williams reviewed gene: AP2S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Familial hypocalciuric hypercalcemia type III MIM 600740; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Renal tubulopathies v1.16 ABCG2 Eleanor Williams reviewed gene: ABCG2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Serum uric acid concentration and susceptibility to gout MIM 138900; Mode of inheritance: Unknown
Renal tubulopathies v1.15 GATM Eleanor Williams gene: GATM was added
gene: GATM was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: GATM was set to
Renal tubulopathies v1.15 GNAS Eleanor Williams gene: GNAS was added
gene: GNAS was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: GNAS was set to
Renal tubulopathies v1.15 MAGED2 Eleanor Williams gene: MAGED2 was added
gene: MAGED2 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: MAGED2 was set to
Renal tubulopathies v1.15 FOXI1 Eleanor Williams Source NHS GMS was added to FOXI1.
Renal tubulopathies v1.15 ATP1A1 Eleanor Williams gene: ATP1A1 was added
gene: ATP1A1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: ATP1A1 was set to
Renal tubulopathies v1.15 CLDN10 Eleanor Williams gene: CLDN10 was added
gene: CLDN10 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CLDN10 was set to
Renal tubulopathies v1.15 WNK4 Eleanor Williams gene: WNK4 was added
gene: WNK4 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: WNK4 was set to
Renal tubulopathies v1.15 WNK1 Eleanor Williams gene: WNK1 was added
gene: WNK1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: WNK1 was set to
Renal tubulopathies v1.15 UMOD Eleanor Williams gene: UMOD was added
gene: UMOD was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: UMOD was set to
Renal tubulopathies v1.15 TRPM6 Eleanor Williams Source NHS GMS was added to TRPM6.
Renal tubulopathies v1.15 SLC9A3R1 Eleanor Williams gene: SLC9A3R1 was added
gene: SLC9A3R1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC9A3R1 was set to
Renal tubulopathies v1.15 SLC5A2 Eleanor Williams gene: SLC5A2 was added
gene: SLC5A2 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC5A2 was set to
Renal tubulopathies v1.15 SLC4A4 Eleanor Williams Source NHS GMS was added to SLC4A4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 SLC4A1 Eleanor Williams Source NHS GMS was added to SLC4A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 SLC34A3 Eleanor Williams gene: SLC34A3 was added
gene: SLC34A3 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC34A3 was set to
Renal tubulopathies v1.15 SLC34A1 Eleanor Williams gene: SLC34A1 was added
gene: SLC34A1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC34A1 was set to
Renal tubulopathies v1.15 SLC2A9 Eleanor Williams gene: SLC2A9 was added
gene: SLC2A9 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC2A9 was set to
Renal tubulopathies v1.15 SLC22A12 Eleanor Williams gene: SLC22A12 was added
gene: SLC22A12 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SLC22A12 was set to
Renal tubulopathies v1.15 SLC12A3 Eleanor Williams Source NHS GMS was added to SLC12A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 SLC12A1 Eleanor Williams Source NHS GMS was added to SLC12A1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 SCNN1G Eleanor Williams gene: SCNN1G was added
gene: SCNN1G was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SCNN1G was set to
Renal tubulopathies v1.15 SCNN1B Eleanor Williams Source NHS GMS was added to SCNN1B.
Renal tubulopathies v1.15 SCNN1A Eleanor Williams gene: SCNN1A was added
gene: SCNN1A was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: SCNN1A was set to
Renal tubulopathies v1.15 REN Eleanor Williams gene: REN was added
gene: REN was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: REN was set to
Renal tubulopathies v1.15 OCRL Eleanor Williams gene: OCRL was added
gene: OCRL was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: OCRL was set to
Renal tubulopathies v1.15 NR3C2 Eleanor Williams gene: NR3C2 was added
gene: NR3C2 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: NR3C2 was set to
Renal tubulopathies v1.15 KLHL3 Eleanor Williams gene: KLHL3 was added
gene: KLHL3 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: KLHL3 was set to
Renal tubulopathies v1.15 KCNJ10 Eleanor Williams gene: KCNJ10 was added
gene: KCNJ10 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: KCNJ10 was set to
Renal tubulopathies v1.15 KCNJ1 Eleanor Williams Source NHS GMS was added to KCNJ1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 KCNA1 Eleanor Williams gene: KCNA1 was added
gene: KCNA1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: KCNA1 was set to
Renal tubulopathies v1.15 HNF1B Eleanor Williams gene: HNF1B was added
gene: HNF1B was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: HNF1B was set to
Renal tubulopathies v1.15 GNA11 Eleanor Williams gene: GNA11 was added
gene: GNA11 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: GNA11 was set to
Renal tubulopathies v1.15 FXYD2 Eleanor Williams gene: FXYD2 was added
gene: FXYD2 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: FXYD2 was set to
Renal tubulopathies v1.15 EHHADH Eleanor Williams Source NHS GMS was added to EHHADH.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 EGF Eleanor Williams gene: EGF was added
gene: EGF was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: EGF was set to
Renal tubulopathies v1.15 CYP24A1 Eleanor Williams gene: CYP24A1 was added
gene: CYP24A1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CYP24A1 was set to
Renal tubulopathies v1.15 CUL3 Eleanor Williams gene: CUL3 was added
gene: CUL3 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CUL3 was set to
Renal tubulopathies v1.15 CTNS Eleanor Williams Source NHS GMS was added to CTNS.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 CLDN19 Eleanor Williams gene: CLDN19 was added
gene: CLDN19 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CLDN19 was set to
Renal tubulopathies v1.15 CLDN16 Eleanor Williams gene: CLDN16 was added
gene: CLDN16 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CLDN16 was set to
Renal tubulopathies v1.15 CLCNKB Eleanor Williams Source NHS GMS was added to CLCNKB.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 CLCNKA Eleanor Williams gene: CLCNKA was added
gene: CLCNKA was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CLCNKA was set to
Renal tubulopathies v1.15 CLCN5 Eleanor Williams gene: CLCN5 was added
gene: CLCN5 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CLCN5 was set to
Renal tubulopathies v1.15 CASR Eleanor Williams gene: CASR was added
gene: CASR was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: CASR was set to
Renal tubulopathies v1.15 CA2 Eleanor Williams Source NHS GMS was added to CA2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 BSND Eleanor Williams Source NHS GMS was added to BSND.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 AVPR2 Eleanor Williams Source NHS GMS was added to AVPR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 ATP6V1B1 Eleanor Williams Source NHS GMS was added to ATP6V1B1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 ATP6V0A4 Eleanor Williams Source NHS GMS was added to ATP6V0A4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 AQP2 Eleanor Williams Source NHS GMS was added to AQP2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Renal tubulopathies v1.15 AP2S1 Eleanor Williams gene: AP2S1 was added
gene: AP2S1 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: AP2S1 was set to
Renal tubulopathies v1.15 ABCG2 Eleanor Williams gene: ABCG2 was added
gene: ABCG2 was added to Renal tubulopathies. Sources: NHS GMS
Mode of inheritance for gene: ABCG2 was set to
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Classified gene: AVPR2 as Green List (high evidence)
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Added comment: Comment on list classification: Promoted to Green.
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Gene: avpr2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.12 AVPR2 Ellen McDonagh gene: AVPR2 was added
gene: AVPR2 was added to Renal tubulopathies. Sources: Other
treatable tags were added to gene: AVPR2.
Mode of inheritance for gene: AVPR2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: AVPR2 were set to 18726898; 27565746; 27117808; 26974133; 26828532
Phenotypes for gene: AVPR2 were set to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation)
Added comment: Added this gene from the Monogenic nephrogenic diabetes insipidus (Version 1.8, code 18) gene panel, after request from the Genomics England Clinical Team. There are >3 unrelated cases/families reported. PMID: 9329382 indicates that heterozygous females may be affected, depending on X-linked skewing. The 'treatable' tag was added due to information available on Orphanet regarding Nephrogenic diabetes insipidus: "Patients should receive a low salt diet with limited potassium and protein intake and take thiazide diuretics in combination with indomethacin. This treatment has changed the life of affected patients, especially infants." summary reviewed by : Dr Patrick NIAUDET - Last update: February 2007 (http://www.orpha.net).
Sources: Other
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Classified gene: AQP2 as Green List (high evidence)
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Added comment: Comment on list classification: Promoted to Green.
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Gene: aqp2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.10 AQP2 Ellen McDonagh gene: AQP2 was added
gene: AQP2 was added to Renal tubulopathies. Sources: Other
treatable tags were added to gene: AQP2.
Mode of inheritance for gene: AQP2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AQP2 were set to 8140421; 7524315; 9048343; 9649557; 9302264; 9745427; 11929850; 12050236; 15509592
Phenotypes for gene: AQP2 were set to Diabetes insipidus, nephrogenic, 125800
Added comment: Added this gene from the Monogenic nephrogenic diabetes insipidus (Version 1.8, code 18) gene panel, after request from the Genomics England Clinical Team. There are >3 unrelated cases/families reported (see publications). Majority of variants reported are missense. Added the 'treatable' tag due to information available on Orphanet regarding Nephrogenic diabetes insipidus: "Patients should receive a low salt diet with limited potassium and protein intake and take thiazide diuretics in combination with indomethacin. This treatment has changed the life of affected patients, especially infants." summary reviewed by : Dr Patrick NIAUDET - Last update: February 2007 (http://www.orpha.net).
Sources: Other
Renal tubulopathies v1.9 Ellen McDonagh Panel name changed from Renal tubular acidosis to Renal tubulopathies
List of related panels changed from to Renal tubular acidosis
Panel types changed to Rare Disease 100K; GMS Rare Disease
Renal tubulopathies v1.8 WDR72 John Sayer gene: WDR72 was added
gene: WDR72 was added to Renal tubular acidosis. Sources: Literature
Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR72 were set to 30028003
Phenotypes for gene: WDR72 were set to distal RTA
Penetrance for gene: WDR72 were set to Complete
Review for gene: WDR72 was set to GREEN
Added comment: Should be added to gene panel
Sources: Literature
Renal tubulopathies v1.8 XPR1 Ellen McDonagh Classified gene: XPR1 as Red List (low evidence)
Renal tubulopathies v1.8 XPR1 Ellen McDonagh Added comment: Comment on list classification: Gene added to this panel by a Reviewer. Made red due to this being a novel gene.
Renal tubulopathies v1.8 XPR1 Ellen McDonagh Gene: xpr1 has been classified as Red List (Low Evidence).
Renal tubulopathies v1.7 FOXI1 Ellen McDonagh Added comment: Comment on mode of inheritance: Homozygous variants were reported in PMID: 29242249.
Renal tubulopathies v1.7 FOXI1 Ellen McDonagh Mode of inheritance for gene: FOXI1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v1.6 FOXI1 Ellen McDonagh Classified gene: FOXI1 as Amber List (moderate evidence)
Renal tubulopathies v1.6 FOXI1 Ellen McDonagh Added comment: Comment on list classification: Gene add to the panel by Reviewer due to new publication reporting three families. Promoted to amber, awaiting Genomics England Clinical Team approval before making Green.
Renal tubulopathies v1.6 FOXI1 Ellen McDonagh Gene: foxi1 has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v1.5 FOXI1 John Sayer gene: FOXI1 was added
gene: FOXI1 was added to Renal tubular acidosis. Sources: Expert Review,Literature
Mode of inheritance for gene: FOXI1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: FOXI1 were set to 29242249
Phenotypes for gene: FOXI1 were set to deafness; renal tubular acidosis
Penetrance for gene: FOXI1 were set to Incomplete
Review for gene: FOXI1 was set to GREEN
Added comment: New gene for RTA and deafness
Sources: Expert Review, Literature
Renal tubulopathies v1.5 XPR1 John Sayer gene: XPR1 was added
gene: XPR1 was added to Renal tubular acidosis. Sources: Literature,Expert Review
Mode of inheritance for gene: XPR1 was set to Unknown
Publications for gene: XPR1 were set to 27799484
Phenotypes for gene: XPR1 were set to Fanconi syndrome; hypophosphatamia
Penetrance for gene: XPR1 were set to unknown
Mode of pathogenicity for gene: XPR1 was set to Other
Review for gene: XPR1 was set to RED
Added comment: Potential novel gene involved in Renal Fanconi and Renal Tubular Acidosis
Sources: Literature, Expert Review
Renal tubulopathies CTNS Sarah Leigh added CTNS to panel
Renal tubulopathies CTNS Sarah Leigh reviewed CTNS
Renal tubulopathies FAH Sarah Leigh added FAH to panel
Renal tubulopathies FAH Sarah Leigh reviewed FAH