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Proteinuric renal disease v6.16 WDR4 Ida Ertmanska Phenotypes for gene: WDR4 were changed from growth deficiency; microcephaly; developmental delay; intellectual disability; proteinuria; nephrotic syndrome to Galloway-Mowat syndrome 6, OMIM:61834; Galloway-Mowat syndrome 6, MONDO:0032691
Proteinuric renal disease v6.15 WDR4 Ida Ertmanska Classified gene: WDR4 as Amber List (moderate evidence)
Proteinuric renal disease v6.15 WDR4 Ida Ertmanska Added comment: Comment on list classification: As reviewed by Luke Stuart and John Sayer, there are now 2 unrelated probands reported in literature with biallelic variants in WDR4 and proteinuria. Hence, this gene should be rated Amber, until more evidence emerges.
Proteinuric renal disease v6.15 WDR4 Ida Ertmanska Gene: wdr4 has been classified as Amber List (Moderate Evidence).
Proteinuric renal disease v6.14 WDR4 Luke Stuart changed review comment from: Renal features including proteinuria and nephrotic syndrome have been noted in a subset of Galloway Mowat Syndrome 6 (GAMOS6) patients:

Braun et al., 2018 (PMID 30079490): A GAMOS family was investigated via WES. WDR4 c.454-2A>C (homozygous) segregated with disease in four siblings, three of whom demonstrated renal involvement (nephrotic range proteinuria). Severity was variable; only one child (B1028-21) developed overt nephrotic syndrome including edema and hypalbuminemia.

Kim et al., 2020 (Case report, journal of Genetic Medicine, 10.5734/jgm.2020.17.2.97): Trio WES identified compound heterozygous WDR4 variants (c.540C>G (p.Ile180Met) and c.494G>A (p.Arg165Gln)) in a patient presenting with seizure, delayed development, and microcephaly at referral. Both variants were classified VUS- rare in Gnomad v4 (0 homozygotes) with equivocal REVEL scores favouring benignity. At 5 years, the patient developed occasional mild proteinuria (1+) with no associated symptoms, progressing to hypoalbuminemia (2.5 mg/dL), proteinuria (3+) and increased urine protein-to-creatinine ratio (3.0) at 6 years. Nephrotic syndrome was diagnosed.

Emerging evidence suggests renal abnormalities as a component of the GAMOS6 phenotype. An amber classification is recommended based on the observation of four individuals from two independent families presenting with proteinuria, two of whom developed overt nephrotic syndrome. Characterisation of additional WDR4-related GAMOS patients is necessary to establish a clear relationship.

WDR4 is associated with Galloway-Mowat syndrome 6 (OMIM #61834) and Microcephaly, growth deficiency, seizures, and brain malformations (OMIM #618346), accessed 08/2026.; to: WDR4 is associated with Galloway-Mowat syndrome 6 (OMIM #61834) and Microcephaly, growth deficiency, seizures, and brain malformations (OMIM #618346), accessed 08/2026.

Renal features including proteinuria and nephrotic syndrome have been noted in a subset of Galloway Mowat Syndrome 6 (GAMOS6) patients:

Braun et al., 2018 (PMID 30079490): A GAMOS family was investigated via WES. WDR4 c.454-2A>C (homozygous) segregated with disease in four siblings, three of whom demonstrated renal involvement (nephrotic range proteinuria). Severity was variable; only one child (B1028-21) developed overt nephrotic syndrome including edema and hypalbuminemia.

Kim et al., 2020 (Case report, journal of Genetic Medicine, 10.5734/jgm.2020.17.2.97): Trio WES identified compound heterozygous WDR4 variants (c.540C>G (p.Ile180Met) and c.494G>A (p.Arg165Gln)) in a patient presenting with seizure, delayed development, and microcephaly at referral. Both variants were classified VUS- rare in Gnomad v4 (0 homozygotes) with equivocal REVEL scores favouring benignity. At 5 years, the patient developed occasional mild proteinuria (1+) with no associated symptoms, progressing to hypoalbuminemia (2.5 mg/dL), proteinuria (3+) and increased urine protein-to-creatinine ratio (3.0) at 6 years. Nephrotic syndrome was diagnosed.

Emerging evidence suggests renal abnormalities as a component of the GAMOS6 phenotype. An amber classification is recommended based on the observation of four individuals from two independent families presenting with proteinuria, two of whom developed overt nephrotic syndrome. Characterisation of additional WDR4-related GAMOS patients is necessary to establish a clear relationship.

Proteinuric renal disease v6.14 WDR4 Luke Stuart reviewed gene: WDR4: Rating: AMBER; Mode of pathogenicity: None; Publications: 30079490; Phenotypes: Galloway-Mowat syndrome 6, OMIM:61834, Galloway-Mowat syndrome 6, MONDO:0032691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v6.2 WDR4 John Sayer gene: WDR4 was added
gene: WDR4 was added to Proteinuric renal disease. Sources: Expert list
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to 30079490; 40533795
Phenotypes for gene: WDR4 were set to growth deficiency; microcephaly; developmental delay; intellectual disability; proteinuria; nephrotic syndrome
Penetrance for gene: WDR4 were set to Complete
Review for gene: WDR4 was set to RED
Added comment: Additional case report not on pubmed 10.5734/jgm.2020.17.2.97
Sources: Expert list