Galloway-Mowat syndrome 1

Summary

Galloway-Mowat syndrome 1 (MONDO:0033005) is a disease caused by WDR73 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: WDR73 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 130

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Galloway-Mowat syndrome 1
Mondo ID	MONDO:0033005
OMIM	251300
DOID	DOID:0060364
UMLS	C4551772
MedGen	1634188
GARD	0015199
Is cancer (heuristic)	no

Also known as: cerebellar ataxia with mental retardation, optic atrophy, and skin abnormalities · Galloway-Mowat syndrome 1 · GAMOS1 · spinocerebellar ataxia, autosomal recessive 5

Data availability: 130 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 1

Related subtypes (9): Galloway-Mowat syndrome 9, Galloway-Mowat syndrome 10, Galloway-Mowat syndrome 6, Galloway-Mowat syndrome 7, Galloway-Mowat syndrome 8, 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

130 retrieved; paginated sample, class counts are floors:

75 uncertain significance, 15 conflicting classifications of pathogenicity, 10 likely pathogenic, 10 pathogenic, 7 pathogenic/likely pathogenic, 6 benign, 5 likely benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
162610	NM_032856.5(WDR73):c.129T>G (p.Tyr43Ter)	WDR73	Pathogenic	no assertion criteria provided
162611	NM_032856.5(WDR73):c.766dup (p.Arg256fs)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1697350	NM_032856.5(WDR73):c.525_565dup (p.Asp189delinsValThrValArgSerTer)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208465	NM_032856.5(WDR73):c.703C>T (p.Gln235Ter)	WDR73	Pathogenic/Likely pathogenic	no assertion criteria provided
208466	NM_032856.5(WDR73):c.400_401del (p.Trp136fs)	WDR73	Pathogenic	no assertion criteria provided
208467	NM_032856.5(WDR73):c.1039C>T (p.His347Tyr)	WDR73	Pathogenic	no assertion criteria provided
208469	NM_032856.5(WDR73):c.940C>T (p.Gln314Ter)	WDR73	Pathogenic	criteria provided, single submitter
208470	NM_032856.5(WDR73):c.287G>A (p.Arg96Lys)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2297702	NM_032856.5(WDR73):c.21G>A (p.Trp7Ter)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3255490	NM_032856.5(WDR73):c.285_287+1dup	WDR73	Pathogenic	criteria provided, single submitter
3370299	NM_032856.5(WDR73):c.475C>T (p.Gln159Ter)	WDR73	Pathogenic	criteria provided, single submitter
3390598	NM_032856.5(WDR73):c.82C>T (p.Arg28Ter)	WDR73	Pathogenic	criteria provided, multiple submitters, no conflicts
4076325	NM_032856.5(WDR73):c.717_847del (p.Ser240fs)	WDR73	Pathogenic	criteria provided, single submitter
4819331	NM_032856.5(WDR73):c.753T>A (p.Cys251Ter)	WDR73	Pathogenic	criteria provided, single submitter
803115	NM_032856.5(WDR73):c.710dup (p.Gly238fs)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807718	NM_032856.5(WDR73):c.706_719dup (p.Ser240fs)	WDR73	Pathogenic	criteria provided, multiple submitters, no conflicts
985008	NM_032856.5(WDR73):c.626G>A (p.Trp209Ter)	WDR73	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1344892	NM_032856.5(WDR73):c.1096_1097del (p.Leu366fs)	WDR73	Likely pathogenic	criteria provided, multiple submitters, no conflicts
208468	NM_032856.5(WDR73):c.68T>A (p.Leu23Gln)	WDR73	Likely pathogenic	criteria provided, single submitter
242543	NM_032856.5(WDR73):c.293T>C (p.Leu98Pro)	WDR73	Likely pathogenic	no assertion criteria provided
2434648	NM_032856.5(WDR73):c.41+1G>C	WDR73	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664753	NM_032856.5(WDR73):c.6_9del (p.Asp2fs)	WDR73	Likely pathogenic	criteria provided, single submitter
3577818	NM_032856.5(WDR73):c.1086_1089delinsCAGCA (p.Asp363fs)	WDR73	Likely pathogenic	criteria provided, single submitter
3577833	NM_032856.5(WDR73):c.699G>A (p.Trp233Ter)	WDR73	Likely pathogenic	criteria provided, single submitter
3577846	NM_032856.5(WDR73):c.388_391del (p.Glu130fs)	WDR73	Likely pathogenic	criteria provided, single submitter
4077743	NM_032856.5(WDR73):c.294_298delinsTCAGAAT (p.Val99fs)	WDR73	Likely pathogenic	criteria provided, single submitter
635182	NM_032856.5(WDR73):c.767G>A (p.Arg256Gln)	WDR73	Likely pathogenic	criteria provided, single submitter
1194019	NM_032856.5(WDR73):c.354T>G (p.Asp118Glu)	WDR73	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1311557	NM_032856.5(WDR73):c.596G>A (p.Arg199Gln)	WDR73	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1896197	NM_032856.5(WDR73):c.1133G>A (p.Arg378His)	WDR73	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 7 · 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
WDR73	Strong	Autosomal recessive	Galloway-Mowat syndrome 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR73	Orphanet:2065	Galloway-Mowat syndrome
WDR73	Orphanet:83472	CAMOS syndrome
ZNF592	Orphanet:83472	CAMOS syndrome
ENG	Orphanet:231160	Familial cerebral saccular aneurysm
ENG	Orphanet:275777	Heritable pulmonary arterial hypertension
ENG	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
ENG	Orphanet:774	Hereditary hemorrhagic telangiectasia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR73	HGNC:25928	ENSG00000177082	Q6P4I2	Integrator complex assembly factor WDR73	gencc,clinvar
ZNF592	HGNC:28986	ENSG00000166716	Q92610	Zinc finger protein 592	clinvar
ENG	HGNC:3349	ENSG00000106991	P17813	Endoglin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR73	Integrator complex assembly factor WDR73	Component of a multiprotein complex required for the assembly of the RNA endonuclease module of the integrator complex.
ZNF592	Zinc finger protein 592	May be involved in transcriptional regulation.
ENG	Endoglin	Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · 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	5.8×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR73	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
ZNF592	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Znf-C2H2_11
ENG	Other/Unknown	no		TGFBR3/Endoglin-like_N

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pituitary gland	1
right lobe of thyroid gland	1
right uterine tube	1
epithelial cell of pancreas	1
pancreatic ductal cell	1
tibialis anterior	1
cardiac atrium	1
right atrium auricular region	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR73	275	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, pituitary gland
ZNF592	241	ubiquitous	yes	pancreatic ductal cell, epithelial cell of pancreas, tibialis anterior
ENG	265	ubiquitous	marker	right lung, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ENG	3,236
WDR73	2,604
ZNF592	1,739

Intra-cohort edges

A	B	Sources
WDR73	ZNF592	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ENG	P17813	3
WDR73	Q6P4I2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF592	Q92610	54.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 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
Interaction of NuRD complexes with transcription factors	1	126.9×	0.008	ZNF592

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
detection of hypoxia	1	2808.7×	0.007	ENG
positive regulation of vascular associated smooth muscle cell differentiation	1	2808.7×	0.007	ENG
cell migration involved in endocardial cushion formation	1	1404.3×	0.007	ENG
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	1	1404.3×	0.007	ENG
atrioventricular canal morphogenesis	1	1404.3×	0.007	ENG
central nervous system vasculogenesis	1	1123.5×	0.007	ENG
cardiac atrium morphogenesis	1	936.2×	0.007	ENG
venous blood vessel morphogenesis	1	802.5×	0.007	ENG
atrial cardiac muscle tissue morphogenesis	1	802.5×	0.007	ENG
dorsal aorta morphogenesis	1	702.2×	0.007	ENG
cardiac ventricle morphogenesis	1	624.1×	0.007	ENG
vascular associated smooth muscle cell development	1	561.7×	0.007	ENG
positive regulation of systemic arterial blood pressure	1	468.1×	0.007	ENG
epithelial to mesenchymal transition involved in endocardial cushion formation	1	468.1×	0.007	ENG
ventricular trabecula myocardium morphogenesis	1	351.1×	0.009	ENG
smooth muscle tissue development	1	351.1×	0.009	ENG
endocardial cushion morphogenesis	1	280.9×	0.010	ENG
regulation of transforming growth factor beta receptor signaling pathway	1	267.5×	0.010	ENG
artery morphogenesis	1	224.7×	0.011	ENG
outflow tract septum morphogenesis	1	216.1×	0.011	ENG
negative regulation of SMAD protein signal transduction	1	200.6×	0.012	ENG
nucleus organization	1	187.2×	0.012	WDR73
negative regulation of endothelial cell proliferation	1	181.2×	0.012	ENG
branching involved in blood vessel morphogenesis	1	175.5×	0.012	ENG
positive regulation of BMP signaling pathway	1	151.8×	0.013	ENG
cell motility	1	133.8×	0.014	ENG
positive regulation of SMAD protein signal transduction	1	127.7×	0.014	ENG
negative regulation of insulin receptor signaling pathway	1	124.8×	0.014	ZNF592
extracellular matrix disassembly	1	122.1×	0.014	ENG
cytoplasmic microtubule organization	1	114.6×	0.014	WDR73

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WDR73	0	0
ZNF592	0	0
ENG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	WDR73, ZNF592, ENG

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR73	0	—
ZNF592	0	—
ENG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.