Galloway-Mowat syndrome 6

Summary

Galloway-Mowat syndrome 6 (MONDO:0032691) is a disease caused by WDR4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: WDR4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Galloway-Mowat syndrome 6
Mondo ID	MONDO:0032691
OMIM	618347
UMLS	C5193043
MedGen	1674560
GARD	0016343
Is cancer (heuristic)	no

Also known as: GAMOS6

Data availability: 19 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Galloway-Mowat syndrome › Galloway-Mowat syndrome 6

Related subtypes (9): Galloway-Mowat syndrome 9, Galloway-Mowat syndrome 10, Galloway-Mowat syndrome 7, Galloway-Mowat syndrome 8, Galloway-Mowat syndrome 1, Galloway-Mowat syndrome 2, X-linked, Galloway-Mowat syndrome 3, Galloway-Mowat syndrome 4, Galloway-Mowat syndrome 5

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 5 benign, 3 pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
438741	NM_018669.6(WDR4):c.491A>C (p.Asp164Ala)	WDR4	Pathogenic	no assertion criteria provided
438742	NM_018669.6(WDR4):c.940dup (p.Leu314fs)	WDR4	Pathogenic	no assertion criteria provided
619602	NM_018669.6(WDR4):c.911_927dup (p.Gln310fs)	WDR4	Pathogenic	criteria provided, single submitter
2503412	NM_018669.6(WDR4):c.509_510delinsTT (p.Arg170Leu)	WDR4	Likely pathogenic	no assertion criteria provided
3337743	NM_018669.6(WDR4):c.428G>A (p.Gly143Glu)	WDR4	Likely pathogenic	criteria provided, single submitter
3377309	NM_018669.6(WDR4):c.727-331G>T	WDR4	Likely pathogenic	criteria provided, single submitter
3697312	NM_018669.6(WDR4):c.627+2T>C	WDR4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
619601	NM_018669.6(WDR4):c.509G>A (p.Arg170Gln)	WDR4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
619605	NM_018669.6(WDR4):c.454-2A>C	WDR4	Likely pathogenic	criteria provided, single submitter
2053918	NM_018669.6(WDR4):c.266G>A (p.Arg89His)	WDR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
619600	NM_018669.6(WDR4):c.509G>T (p.Arg170Leu)	WDR4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2072980	NM_018669.6(WDR4):c.2T>C (p.Met1Thr)	WDR4	Uncertain significance	criteria provided, multiple submitters, no conflicts
3777743	NM_018669.6(WDR4):c.724del (p.Gln242fs)	WDR4	Uncertain significance	criteria provided, single submitter
1221407	NM_018669.6(WDR4):c.796C>T (p.Pro266Ser)	WDR4	Benign	criteria provided, multiple submitters, no conflicts
1227334	NM_018669.6(WDR4):c.567-16T>C	WDR4	Benign	criteria provided, multiple submitters, no conflicts
1229045	NM_018669.6(WDR4):c.1045+38C>T	WDR4	Benign	criteria provided, multiple submitters, no conflicts
1234975	NM_018669.6(WDR4):c.1169G>A (p.Arg390Gln)	WDR4	Benign	criteria provided, multiple submitters, no conflicts
1238762	NM_018669.6(WDR4):c.213G>C (p.Lys71Asn)	WDR4	Benign	criteria provided, multiple submitters, no conflicts
773615	NM_018669.6(WDR4):c.33G>A (p.Gly11=)	WDR4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
WDR4	Strong	Autosomal recessive	Galloway-Mowat syndrome 6	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR4	Orphanet:2065	Galloway-Mowat syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR4	HGNC:12756	ENSG00000160193	P57081	tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR4	tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4	Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR4	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, Trm82

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR4	214	ubiquitous	marker	gingival epithelium, mucosa of transverse colon, gingiva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR4	2,073

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WDR4	P57081	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA modification in the nucleus and cytosol	1	292.8×	0.003	WDR4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tRNA (guanine-N7)-methylation	1	8426.0×	4e-04	WDR4
tRNA modification	1	601.9×	0.002	WDR4
DNA damage response	1	53.5×	0.019	WDR4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WDR4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	WDR4

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.