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| 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 v4.5 | 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 v4.2 | 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. |
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| 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 |
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| 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 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. |
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| 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. |
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| 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 v2.61 | RRAGD | Eleanor Williams Phenotypes for gene: RRAGD were changed from hypomagnesaemia; cardiomyopathy to hypomagnesaemia; cardiomyopathy; tubular renal disease-cardiomyopathy syndrome, MONDO:0019130 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v2.58 | 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 v2.54 | 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 |
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| 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 |
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| 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. |
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| 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 v2.50 | 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 v2.39 | 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 | 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 v2.36 | 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 | 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 v2.30 | 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 |
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| 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 v2.26 | 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 |
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| 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 v2.14 | 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 |
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| 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 v2.12 | 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 |
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| 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 v2.10 | 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 |
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| 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 v2.4 | 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 v2.0 | 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 |
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| 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 |
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| 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. |
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| 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. |
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| 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 v1.134 | 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. |
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| 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. |
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| Renal tubulopathies v1.129 | KCNJ10 | Eleanor Williams Added comment: Comment on phenotypes: Removed phenotype that does not have renal presentation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v1.123 | 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. |
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| 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 v1.121 | 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. |
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| 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. |
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| 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. |
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| 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 |
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| 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 |
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| 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. |
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| 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. |
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| 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. |
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| 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 v1.83 | Eleanor Williams List of related panels changed from Renal tubular acidosis to Renal tubular acidosis; R198 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. |
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| 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. |
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| 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 |
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| 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. |
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| 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 |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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. |
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| 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 |
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| 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 v1.75 | 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 v1.65 | 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 v1.61 | 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 v1.53 | REN | Eleanor Williams Phenotypes for gene: REN were changed from to Hyperuricemic nephropathy, familial juvenile 2, 613092; Renal tubular dysgenesis 267430 AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.45 | HNF1B | Eleanor Williams Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, 137920; Diabetes mellitus, noninsulin-dependent, 125853 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.43 | 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 v1.36 | 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 v1.27 | 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 v1.22 | 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 v1.20 | WDR72 | Eleanor Williams Phenotypes for gene: WDR72 were changed from distal RTA to distal RTA; hereditary distal renal tubular acidosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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 | 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 v1.15 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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