VPS41

Chr 7p14.1

VPS41 subunit of HOPS complex

Aliases:: HVSP41
MANE:: ENST00000310301.9

OMIM: 605485 ↗NCBI: 27072 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

VPS41 · P49754

v62025-08-01

Predicted Aligned Error matrix for VPS41 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

86.4/ 100

Confident

854 residues

Confidence breakdown

Very high(≥ 90)48%
Confident(70–90)46%
Low(50–70)2%
Very low(< 50)4%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodegenerative disease
0.56
Dystonia
0.52
spinocerebellar ataxia, autosomal recessive 29
0.51
Intellectual disability
0.46
cerebellar ataxia
0.44
Ataxia
0.44
Abnormality of the skeletal system
0.40
lysosomal storage disease
0.37
COVID-19
0.37
Autosomal recessive cerebellar ataxia - saccadic intrusion
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Vacuolar protein sorting-associated protein 41 homolog

Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the HOPS endosomal tethering complex. This complex is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes (PubMed:23351085, PubMed:33851776). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes implicated in degradation of endocytosed cargo (PubMed:23167963, PubMed:25445562, PubMed:25908847, PubMed:9159129). Required for fusion of autophagosomes with lysosomes (PubMed:25783203, PubMed:37821429). Links the HOPS complex to endosomal Rab7 via its association with RILP and to lysosomal membranes via its association with ARL8B, suggesting that these interactions may bring the compartments to close proximity for fusion (PubMed:21802320, PubMed:25445562, PubMed:25908847). Involved in the direct trans-Golgi network to late endosomes transport of lysosomal membrane proteins independently of HOPS (PubMed:23322049). Involved in sorting to the regulated secretory pathway presumably implicating the AP-3 adapter complex (By similarity). May play a role in HOPS-independent function in the regulated secretory pathway (PubMed:24210660)