WDR37

protein-coding

WD repeat domain 37, the group of WD repeat domain containing

Gene summary

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014023.4

Inheritance

ClinVar variants

P:10U:99B:45

Top phenotype

Neurooculocardiogenitourinary syndrome

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr10:1,049,538-1,160,991

External References & Databases

Ensembl (ENSG00000047056)

Transcript & Mutation Effects

hg38 • Region Span ~111.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurooculocardiogenitourinary syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032850

Submitter: Labcorp Genetics (formerly Invitae)

neurooculocardiogenitourinary syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032850

Submitter: G2P

neurooculocardiogenitourinary syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032850

Submitter: PanelApp Australia

neurooculocardiogenitourinary syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032850

Submitter: Ambry Genetics

neurooculocardiogenitourinary syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032850

Submitter: ClinGen

The *WDR37* gene is located on chromosome 10 at 10p15.3 and encodes WD Repeat Domain 37, a member of the WD40 repeat-containing protein family, broadly involved in protein-protein interaction and molecular recognition in widespread biological processes. The specific function of *WDR37* is unknown. *WDR37* was first reported in relation to autosomal dominant neurooculocardiogenitourinary syndrome (NOCGUS) in 2019 (Reis et al., PMID:31327510 and Kanca et al., PMID:31327508). This multi-system disorder is characterized by severe complex ocular anomalies, dysmorphic craniofacial features, structural brain anomalies with severe neurological impairment, congenital heart defects, as well as skeletal (mostly spinal), genitourinary, and gastrointestinal anomalies, with feeding issues and poor growth. Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least 9 unique pathogenic/likely pathogenic variants (8 missense, 1 intronic deletion/splice) have been reported in 13 unrelated probands in five publications (PMIDs: 31327510, 31327508, 32530092, 34642815, 38044197) and are included in this curation. This gene-disease relationship is also supported by experimental evidence from protein-protein interaction data and model systems including drosophila, zebrafish, and mouse (PMIDs: 31327510, 31327508, 27626380). Functional studies are consistent with a dominant-negative mechanism of disease predominantly due to missense variants. In summary, there is definitive evidence to support relationship between *WDR37* and neurooculocardiogenitourinary syndrome. No convincing contradictory evidence has emerged to date. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date October 18th, 2024 (SOP Version 11).

Clinical Genomic Database (CGD)

Neurooculocardiogenitourinary syndromeAD

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 31327508; 31327510

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR37 variants in ClinVar

14 Conditions Cataloged

Inborn genetic diseasesTotal: 71

not providedTotal: 46

Neurooculocardiogenitourinary syndromeTotal: 26

WDR37-related disorderTotal: 23

not specifiedTotal: 11

Intellectual disabilityTotal: 5

Isolated cerebellar hypoplasia/agenesisTotal: 4

EpilepsyTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014023.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	24 clinvar		27
missense		9 clinvar	90 clinvar	20 clinvar	1 clinvar	120
nonsense			2 clinvar			2
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	10	99	44	1	154

Highest pathogenic variant AF is 0.0000054817347

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014023.4	RefSeq	NP_054742.2	13	MANE Select
ENST00000263150.9	Ensembl	ENSP00000263150.4	13	MANE Select
ENST00000358220.5	Ensembl	ENSP00000350954.1	13	Standard
ENST00000358220.6	Ensembl	ENSP00000350954.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

preribosome, large subunit precursor
PeBoW complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358220
Coding exons: 13
Length: 82760
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.31	205	322	0.637	0.0000214	3219
Missense (PolyPhen)		82	145.76	0.56255		1357
Synonymous	-0.105	138	136	1.01	0.0000101	992
Loss of Function	3.93	6	28.7	0.209	0.00000149	303

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.213
RVIS EVS: -0.91
RVIS percentile EVS: 9.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.901

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium