VPS25

vacuolar protein sorting 25 homolog, the group of ESCRT-II

Basic information

Region (hg38): 17:42773449-42779599

Links

ENSG00000131475

∙ NCBI:84313 ∙ OMIM:610907 ∙ HGNC:28122 ∙ Uniprot:Q9BRG1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS25 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS25 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			6 clinvar		1 clinvar	7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	1

Variants in VPS25

This is a list of pathogenic ClinVar variants found in the VPS25 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
17-42773524-T-A	not specified	Uncertain significance (Apr 22, 2022)	2285215
17-42773812-A-C	not specified	Uncertain significance (Feb 23, 2023)	2456286
17-42774672-A-G		Benign (Jun 13, 2018)	791412
17-42775432-G-A	not specified	Uncertain significance (Nov 07, 2023)	3188862
17-42776317-G-A	not specified	Uncertain significance (Jan 20, 2023)	2463447
17-42778957-A-T	not specified	Uncertain significance (Dec 19, 2022)	2337478
17-42778966-G-A	not specified	Uncertain significance (Dec 17, 2021)	2267792
17-42779025-G-A	not specified	Uncertain significance (May 15, 2024)	3332221

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS25	protein_coding	protein_coding	ENST00000253794	6	6164

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0776	0.912	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	59	101	0.585	0.00000530	1159
Missense in Polyphen		15	37.049	0.40487		417
Synonymous	-0.516	47	42.7	1.10	0.00000248	314
Loss of Function	2.24	4	12.6	0.317	5.50e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. The ESCRT-II complex may be involved in facilitating the budding of certain RNA viruses. {ECO:0000269|PubMed:18723511}.;
Pathway: Endocytosis - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Endosomal Sorting Complex Required For Transport (ESCRT) (Consensus)

Recessive Scores

pRec: 0.136

Intolerance Scores

loftool: 0.398
rvis_EVS: 0.08
rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

pHI: 0.544
hipred: Y
hipred_score: 0.783
ghis: 0.598

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vps25
Phenotype: growth/size/body region phenotype; craniofacial 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype;

Gene ontology

Biological process: negative regulation of epidermal growth factor-activated receptor activity;endosomal transport;macroautophagy;multivesicular body assembly;protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Cellular component: ESCRT II complex;nucleus;nucleoplasm;cytoplasm;cytosol;endosome membrane;extracellular exosome
Molecular function: structural molecule activity;protein binding;protein homodimerization activity;protein N-terminus binding