VCPIP1

protein-coding

valosin containing protein interacting protein 1, the group of OTU domain containing

Gene summary

Enables cysteine-type deubiquitinase activity. Involved in protein deubiquitination; protein-DNA covalent cross-linking repair; and regulation of protein localization to chromatin. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_025054.5

Inheritance

—

ClinVar variants

U:107B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr8:66,628,487-66,667,231

External References & Databases

Ensembl (ENSG00000175073)

Transcript & Mutation Effects

hg38 • Region Span ~38.7 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 VCPIP1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 103

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025054.5. 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			1 clinvar			1
missense			105 clinvar	1 clinvar		106
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	107	1	0	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025054.5	RefSeq	NP_079330.2	3	MANE Select
ENST00000310421.5	Ensembl	ENSP00000309031.4	3	MANE Select
ENST00001133129.1	Ensembl	ENSP00000806028.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
vcpip1	Danio rerio	Structure: caudal fin upper lobe Quality: fused with abnormal

Gene / Model

Organism

Observed Phenotype

vcpip1

Danio rerio

Structure: caudal fin upper lobe

Quality: fused with

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Ovarian tumor domain proteases
Deubiquitination

Biological Process

mitotic cell cycle
endoplasmic reticulum membrane fusion
protein ubiquitination
protein K11-linked deubiquitination
protein K48-linked deubiquitination

Molecular Function

thiol-dependent ubiquitin-specific protease activity

Cellular Component

cytoplasm
endoplasmic reticulum lumen
Golgi stack

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310421
Coding exons: 3
Length: 38731
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125746
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.56	391	645	0.606	0.0000306	7990
Missense (PolyPhen)		62	212.26	0.29209		2643
Synonymous	0.0931	241	243	0.992	0.0000116	2491
Loss of Function	5.71	1	39.9	0.0250	0.00000237	492

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a deubiquitinating enzyme. Necessary for VCP- mediated reassembly of Golgi stacks after mitosis. May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains. {ECO:0000250, ECO:0000269|PubMed:23827681}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.0703
RVIS EVS: -0.84
RVIS percentile EVS: 11.28

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.954

Gene Damage Prediction

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