WDR74

protein-coding

WD repeat domain 74, the group of WD repeat domain containing

Gene summary

Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001369450.1

Inheritance

—

ClinVar variants

U:57B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr11:62,832,342-62,841,809

External References & Databases

Ensembl (ENSG00000133316)

Transcript & Mutation Effects

hg38 • Region Span ~9.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR74 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001369450.1. 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			1 clinvar		1 clinvar	2
missense			51 clinvar	1 clinvar	2 clinvar	54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	57	1	3	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001369450.1	RefSeq	NP_001356379.1	11	MANE Select
ENST00000278856.9	Ensembl	ENSP00000278856.4	11	MANE Select
NM_001307977.1	RefSeq	NP_001294906.1	10	Standard
NM_001369447.1	RefSeq	NP_001356376.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

blastocyst formation
rRNA processing
RNA metabolic process
ribosomal large subunit biogenesis

Molecular Function

protein binding

Cellular Component

nuclear exosome (RNase complex)
nucleus
nucleolus
preribosome, large subunit precursor

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000525239
Coding exons: 11
Length: 9468
Individuals with no LoFs: 124522
Homozygous LoFs: 0
Heterozygous LoFs: 120
Defined: 124642
p: 0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.923	185	224	0.826	0.0000119	2445
Missense (PolyPhen)		40	62.952	0.6354		656
Synonymous	1.19	72	86.0	0.837	0.00000399	789
Loss of Function	1.13	16	21.7	0.739	0.00000103	234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00065	0.00065	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00017	0.00017	rare
Finnish	0.0022	0.0022	notable
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00017	0.00016	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory protein of the MTREX-exosome complex involved in the synthesis of the 60S ribosomal subunit (PubMed:26456651). Participates in an early cleavage of the pre-rRNA processing pathway in cooperation with NVL (PubMed:29107693). Required for blastocyst formation, is necessary for RNA transcription, processing and/or stability during preimplantation development (By similarity). {ECO:0000250|UniProtKB:Q8VCG3, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:29107693}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.648
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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