MVP

protein-coding

major vault protein

Gene summary

This gene encodes the major component of the vault complex. Vaults are multi-subunit ribonucleoprotein structures that may be involved in nucleo-cytoplasmic transport. The encoded protein may play a role in multiple cellular processes by regulating the MAP kinase, JAK/STAT and phosphoinositide 3-kinase/Akt signaling pathways. The encoded protein also plays a role in multidrug resistance, and expression of this gene may be a prognostic marker for several types of cancer. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

MANE transcript

NM_005115.5

Inheritance

—

ClinVar variants

U:125B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr16:29,820,394-29,848,039

External References & Databases

Ensembl (ENSG00000013364)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 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 MVP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005115.5. 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			2 clinvar	5 clinvar	1 clinvar	8
missense			116 clinvar	6 clinvar	3 clinvar	125
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	125	11	4	140

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005115.5	RefSeq	NP_005106.2	14	MANE Select
ENST00000357402.10	Ensembl	ENSP00000349977.5	14	MANE Select
NM_001293204.1	RefSeq	NP_001280133.1	14	Standard
NM_001293205.1	RefSeq	NP_001280134.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mvp	Danio rerio	Structure: post-vent region Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

mvp

Danio rerio

Structure: post-vent region

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System
EGFR1

Biological Process

protein transport
negative regulation of signaling
negative regulation of protein autophosphorylation
ERBB signaling pathway
neutrophil degranulation

Molecular Function

protein binding
protein kinase binding
protein phosphatase binding
identical protein binding

Cellular Component

extracellular region
nucleus
nuclear pore
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357402
Coding exons: 14
Length: 27641
Individuals with no LoFs: 125603
Homozygous LoFs: 0
Heterozygous LoFs: 145
Defined: 125748
p: 0.000577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.02	431	566	0.762	0.0000376	5684
Missense (PolyPhen)		227	298.44	0.76061		2953
Synonymous	0.564	235	246	0.954	0.0000162	1915
Loss of Function	2.87	18	36.8	0.489	0.00000183	412

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.0019	0.0016	notable
European (Non-Finnish)	0.00065	0.00063	rare
South Asian	0.00036	0.00036	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for normal vault structure. Vaults are multi- subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo- cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases. {ECO:0000269|PubMed:15133037, ECO:0000269|PubMed:16418217, ECO:0000269|PubMed:16441665}.;

Recessive Scores

pRec: 0.219

Intolerance Scores

LoFtool: 0.797
RVIS EVS: -0.81
RVIS percentile EVS: 12.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.992

Gene Damage Prediction

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