VPS18

VPS18 core subunit of CORVET and HOPS complexes, the group of HOPS complex|CORVET complex

Basic information

Region (hg38): 15:40894450-40903975

Links

ENSG00000104142

∙ NCBI:57617 ∙ OMIM:608551 ∙ HGNC:15972 ∙ Uniprot:Q9P253 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

leukodystrophy (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS18 gene.

not_specified (149 variants)
not_provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020857.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	1 clinvar	3
missense			147 clinvar	3 clinvar		150
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	147	5	1

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS18	protein_coding	protein_coding	ENST00000220509	5	9546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.476	0.524	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.627	560	603	0.928	0.0000423	6260
Missense in Polyphen		122	158.73	0.76858		1708
Synonymous	-0.217	257	253	1.02	0.0000158	2063
Loss of Function	4.38	8	36.6	0.219	0.00000238	369

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000265
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

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 as a core component of the putative HOPS and CORVET endosomal tethering complexes which are 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. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in dendrite development of Pukinje cells (By similarity). {ECO:0000250|UniProtKB:Q8R307, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25783203}.;
Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

pRec: 0.141

Intolerance Scores

loftool: 0.407
rvis_EVS: -1.46
rvis_percentile_EVS: 3.86

Haploinsufficiency Scores

pHI: 0.272
hipred: Y
hipred_score: 0.641
ghis: 0.512

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vps18
Phenotype: growth/size/body region phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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);

Zebrafish Information Network

Gene name: vps18
Affected structure: iridophore
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: intracellular protein transport;vesicle docking involved in exocytosis;autophagy;endosome organization;vacuole organization;lysosome organization;endosome to lysosome transport;regulation of SNARE complex assembly;viral entry into host cell;regulation of synaptic vesicle exocytosis
Cellular component: lysosome;lysosomal membrane;endosome;early endosome;late endosome;autophagosome;actin filament;AP-3 adaptor complex;clathrin-coated vesicle;HOPS complex;late endosome membrane;CORVET complex;presynapse;glutamatergic synapse
Molecular function: actin binding;protein binding;syntaxin binding;protein binding, bridging;metal ion binding