WDR41

protein-coding

WD repeat domain 41, the group of WD repeat domain containing|SWC tripartite complex

Gene summary

Enables GTPase activator activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_018268.4

Inheritance

—

ClinVar variants

U:78B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr5:77,425,970-77,620,611

External References & Databases

Ensembl (ENSG00000164253)

Transcript & Mutation Effects

hg38 • Region Span ~194.6 kb

Loading mutation effect viewer...

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 WDR41 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018268.4. 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						0
missense			70 clinvar	2 clinvar		72
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	78	2	0	80

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018268.4	RefSeq	NP_060738.2	13	MANE Select
ENST00000296679.9	Ensembl	ENSP00000296679.4	13	MANE Select
ENST00000503035.5	Ensembl	ENSP00000421166.1	2	Standard
ENST00000504895.5	Ensembl	ENSP00000426141.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

autophagy
regulation of autophagy

Molecular Function

protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasm
lysosomal membrane
guanyl-nucleotide exchange factor complex
Atg1/ULK1 kinase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296679
Coding exons: 13
Length: 194642
Individuals with no LoFs: 125556
Homozygous LoFs: 0
Heterozygous LoFs: 192
Defined: 125748
p: 0.000764

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.165	245	238	1.03	0.0000115	2975
Missense (PolyPhen)		79	77.029	1.0256		955
Synonymous	0.474	83	88.7	0.936	0.00000445	875
Loss of Function	1.07	24	30.4	0.790	0.00000156	332

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00093	0.00092	rare
Latino/Admixed American	0.00076	0.00075	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00042	0.00037	rare
European (Non-Finnish)	0.00081	0.00080	rare
South Asian	0.00089	0.00088	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Non-catalytic component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27193190, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:27103069). The C9orf72- SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity (PubMed:27103069, PubMed:27617292). {ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531}.;

Intolerance Scores

LoFtool: 0.933
RVIS EVS: 0.6
RVIS percentile EVS: 82.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.144

Gene Damage Prediction

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