VPS39

VPS39 subunit of HOPS complex, the group of MicroRNA protein coding host genes|HOPS complex

Basic information

Region (hg38): 15:42158701-42208307

Links

ENSG00000166887

∙ NCBI:23339 ∙ OMIM:612188 ∙ HGNC:20593 ∙ Uniprot:Q96JC1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizophrenia	AD	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	23042115

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS39 gene.

not_specified (85 variants)
not_provided (3 variants)
Cerebellar_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS39 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015289.5. 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			85 clinvar			85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	86	2	1

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS39	protein_coding	protein_coding	ENST00000318006	25	49616

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.78e-11	1.00	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.65	314	477	0.659	0.0000252	5751
Missense in Polyphen		70	128	0.54688		1556
Synonymous	0.00911	187	187	0.999	0.0000101	1643
Loss of Function	3.44	27	54.4	0.496	0.00000280	629

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000750	0.000749
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.000327	0.000326
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000320	0.000316
Middle Eastern	0.000327	0.000326
South Asian	0.0000327	0.0000327
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2- dependent transcription. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation. {ECO:0000269|PubMed:12941698}.;
Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;TGF_beta_Receptor (Consensus)

Recessive Scores

pRec: 0.115

Intolerance Scores

loftool: 0.741
rvis_EVS: -0.84
rvis_percentile_EVS: 11.28

Haploinsufficiency Scores

pHI: 0.280
hipred: Y
hipred_score: 0.575
ghis: 0.598

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.813

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vps39
Phenotype

Zebrafish Information Network

Gene name: vps39
Affected structure: iridophore
Phenotype tag: abnormal
Phenotype quality: reflectivity

Gene ontology

Biological process: intracellular protein transport;autophagy;endosome to lysosome transport;vesicle-mediated transport;endosomal vesicle fusion;late endosome to lysosome transport;retrograde transport, endosome to plasma membrane
Cellular component: lysosomal membrane;AP-3 adaptor complex;HOPS complex;late endosome membrane
Molecular function