VPS28

protein-coding

VPS28 subunit of ESCRT-I, the group of ESCRT-I

Gene summary

This gene encodes a protein subunit of the ESCRT-I complex (endosomal complexes required for transport), which functions in the transport and sorting of proteins into subcellular vesicles. This complex can also be hijacked to facilitate the budding of enveloped viruses from the cell membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

MANE transcript

NM_016208.4

Inheritance

—

ClinVar variants

U:35B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr8:144,423,601-144,428,563

External References & Databases

Ensembl (ENSG00000160948)

Transcript & Mutation Effects

hg38 • Region Span ~5.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS28 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 35

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016208.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	4 clinvar		6
missense			24 clinvar	2 clinvar		26
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	35	6	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 157 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016208.4	RefSeq	NP_057292.1	9	MANE Select
ENST00000292510.6	Ensembl	ENSP00000292510.3	9	MANE Select
NM_183057.3	RefSeq	NP_898880.1	8	Standard
ENST00000377348.6	Ensembl	ENSP00000366565.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Disease
Vesicle-mediated transport
Membrane Trafficking
Assembly Of The HIV Virion

Biological Process

endosomal transport
macroautophagy
viral life cycle
negative regulation of protein ubiquitination
multivesicular body assembly

Molecular Function

protein binding
ubiquitin binding
protein-containing complex binding

Cellular Component

ESCRT I complex
cytoplasm
endosome
early endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377348
Coding exons: 8
Length: 4932
Individuals with no LoFs: 125552
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125561
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.871	127	158	0.805	0.0000104	1508
Missense (PolyPhen)		20	42.377	0.47196		421
Synonymous	-1.21	75	62.8	1.19	0.00000429	452
Loss of Function	2.19	4	12.3	0.326	7.02e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.000020	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. {ECO:0000269|PubMed:11916981}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.215
RVIS EVS: -0.4
RVIS percentile EVS: 26.53

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

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