VPS41

VPS41 subunit of HOPS complex, the group of Ring finger proteins|HOPS complex

Basic information

Region (hg38): 7:38722974-38932394

Links

ENSG00000006715 ∙ NCBI:27072 ∙ OMIM:605485 ∙ HGNC:12713 ∙ Uniprot:P49754 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome (Supportive), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 29 (Limited), mode of inheritance: Unknown
• spinocerebellar ataxia, autosomal recessive 29 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 29	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	32808683; 33764426; 33851776

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS41 gene.

• Inborn_genetic_diseases (95 variants)
• not_provided (25 variants)
• Spinocerebellar_ataxia,_autosomal_recessive_29 (16 variants)
• Hyperimmunoglobulin_D_with_periodic_fever (1 variants)
• VPS41-related_condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS41 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014396.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense	2	2	101	3	1	109
nonsense		2				2
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)	2	1	3			6
Total	4	5	105	7	2

Highest pathogenic variant AF is 0.000195923

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS41	protein_coding	protein_coding	ENST00000310301	29	209432

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.42e-18	0.969	125522	0	224	125746	0.000891

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	358	446	0.803	0.0000223	5671
Missense in Polyphen		98	133.02	0.73672		1673
Synonymous	-0.387	157	151	1.04	0.00000753	1459
Loss of Function	2.55	37	57.9	0.639	0.00000312	712

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00112
Ashkenazi Jewish	0.00477	0.00477
East Asian	0.00205	0.00196
Finnish	0.000237	0.000231
European (Non-Finnish)	0.000620	0.000615
Middle Eastern	0.00205	0.00196
South Asian	0.000797	0.000752
Other	0.00164	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act in part as a core component of the putative HOPS endosomal tethering 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). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes implicated in degradation of endocytosed cargo (PubMed:9159129, PubMed:23167963, PubMed:25445562, PubMed:25908847). Required for fusion of autophagosomes with lysosomes (PubMed:25783203). May link 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: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 adaptor complex (By similarity). May play a role in HOPS-independent function in the regulated secretory pathway (PubMed:24210660). {ECO:0000250|UniProtKB:D3ZVH6, ECO:0000269|PubMed:23167963, ECO:0000269|PubMed:23322049, ECO:0000269|PubMed:25445562, ECO:0000269|PubMed:25783203, ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:9159129, ECO:0000305|PubMed:23167963, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:24210660, ECO:0000305|PubMed:25445562}.
• Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.971
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.82

Haploinsufficiency Scores

• pHI: 0.388
• hipred: N
• hipred_score: 0.488
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps41
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype

Gene ontology

• Biological process: intracellular protein transport;autophagy;endosome to lysosome transport;endosomal vesicle fusion;regulation of SNARE complex assembly;vacuole fusion, non-autophagic;regulated exocytosis;late endosome to lysosome transport
• Cellular component: lysosomal membrane;early endosome;late endosome;Golgi apparatus;Golgi-associated vesicle;endosome membrane;microtubule cytoskeleton;AP-3 adaptor complex;clathrin-coated vesicle;HOPS complex;late endosome membrane;clathrin complex
• Molecular function: protein binding;microtubule binding;identical protein binding;protein self-association;metal ion binding