Proteinuric renal disease

Gene: WDR4

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.

Created: 17 Aug 2026, 12:28 p.m. | Last Modified: 17 Aug 2026, 12:28 p.m.

Panel Version: 6.15

I don't know

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.

Created: 14 Aug 2026, 3:54 p.m. | Last Modified: 14 Aug 2026, 3:55 p.m.

Panel Version: 6.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome 6, OMIM:61834; Galloway-Mowat syndrome 6, MONDO:0032691

Publications

• 30079490

Red List (low evidence)

Additional case report not on pubmed 10.5734/jgm.2020.17.2.97
Sources: Expert list

Created: 6 Jul 2026, 4:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
growth deficiency; microcephaly; developmental delay; intellectual disability; proteinuria; nephrotic syndrome

Publications

• 30079490
• 40533795