VMP1

protein-coding

vacuole membrane protein 1, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a transmembrane protein that plays a key regulatory role in the process of autophagy. The ectopic overexpression of the encoded protein in cultured cells triggers autophagy even under nutrient-rich conditions. This gene is overexpressed in pancreatitis affected acinar cells where the encoded protein mediates sequestration and degradation of potentially deleterious activated zymogen granules in a process termed, zymophagy. [provided by RefSeq, Jul 2016]

Previous symbols:

TMEM49

MANE transcript

NM_030938.5

Inheritance

—

ClinVar variants

U:39B:2

Top phenotype

Monoclonal B-Cell Lymphocytosis

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr17:59,707,192-59,842,255

External References & Databases

Ensembl (ENSG00000062716)

Transcript & Mutation Effects

hg38 • Region Span ~135.1 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 VMP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 28

Monoclonal B-Cell LymphocytosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030938.5. 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			2
missense			28 clinvar	2 clinvar		30
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	39	2	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030938.5	RefSeq	NP_112200.2	11	MANE Select
ENST00000262291.9	Ensembl	ENSP00000262291.3	11	MANE Select
NM_001329394.2	RefSeq	NP_001316323.1	11	Standard
NM_001329395.2	RefSeq	NP_001316324.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
vmp1	Danio rerio	Structure: hepatocyte Quality: increased size abnormal

Gene / Model

Organism

Observed Phenotype

vmp1

Danio rerio

Structure: hepatocyte

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Autophagy - animal - Homo sapiens (human)
Nanoparticle triggered autophagic cell death

Biological Process

autophagosome assembly
autophagy
Golgi organization
embryo implantation
cell junction assembly

Molecular Function

protein binding

Cellular Component

phagophore assembly site
autophagosome membrane
nucleolus
endoplasmic reticulum
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262291
Coding exons: 11
Length: 135064
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125745
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.25	126	220	0.573	0.0000110	2651
Missense (PolyPhen)		15	68.745	0.2182		821
Synonymous	1.09	64	76.2	0.840	0.00000386	764
Loss of Function	3.92	3	23.5	0.128	9.93e-7	293

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stress-induced protein that, when overexpressed, promotes formation of intracellular vacuoles followed by cell death. May be involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis. Plays a role in the initial stages of the autophagic process through its interaction with BECN1 (By similarity). Involved in cell-cell adhesion. Plays an essential role in formation of cell junctions (PubMed:17724469). Required for autophagosome formation (PubMed:30093494). {ECO:0000250|UniProtKB:Q91ZQ0, ECO:0000269|PubMed:17724469, ECO:0000269|PubMed:30093494}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

RVIS EVS: -0.41
RVIS percentile EVS: 26.23

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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