VMP1

Summary

VMP1 (vacuole membrane protein 1, HGNC:29559) is a protein-coding gene on chromosome 17q23.1, encoding Vacuole membrane protein 1 (Q96GC9). Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. It is a common-essential gene (DepMap: required in 98.1% of cancer cell lines).

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.

Source: NCBI Gene 81671 — RefSeq curated summary.

At a glance

• GWAS associations: 39
• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_030938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29559
Approved symbol	VMP1
Name	vacuole membrane protein 1
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	EPG3, TANGO5
Ensembl gene	ENSG00000062716
Ensembl biotype	protein_coding
OMIM	611753
Entrez	81671

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 29 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000262291, ENST00000585847, ENST00000586245, ENST00000587259, ENST00000587470, ENST00000587945, ENST00000588131, ENST00000588617, ENST00000588915, ENST00000589823, ENST00000590850, ENST00000591315, ENST00000591782, ENST00000591877, ENST00000592106, ENST00000592619, ENST00000592790, ENST00000593168, ENST00000710770, ENST00000710771, ENST00000891487, ENST00000891488, ENST00000891489, ENST00000891490, ENST00000891491, ENST00000891492, ENST00000891493, ENST00000891494, ENST00000891495, ENST00000891496, ENST00000891497, ENST00000891498, ENST00000891499, ENST00000891500, ENST00000891501, ENST00000938025, ENST00000938026, ENST00000938027, ENST00000958712, ENST00000958713

RefSeq mRNA: 10 — MANE Select: NM_030938 NM_001329394, NM_001329395, NM_001329396, NM_001329397, NM_001329398, NM_001329399, NM_001329400, NM_001329401, NM_001329402, NM_030938

CCDS: CCDS11619

Canonical transcript exons

ENST00000262291 — 12 exons

Exon	Start	End
ENSE00003459735	59817712	59817773
ENSE00003511298	59808796	59808876
ENSE00003550286	59731421	59731522
ENSE00003569645	59838295	59838397
ENSE00003641327	59811670	59811786
ENSE00003726177	59735338	59735473
ENSE00004013151	59764971	59765138
ENSE00004013152	59737453	59737543
ENSE00004013156	59707654	59707748
ENSE00004013159	59773754	59773885
ENSE00004013160	59738837	59738947
ENSE00004013163	59839768	59842255

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 287.4922 / max 12243.1593, expressed in 1826 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162000	130.7817	1783
161976	62.9289	1824
162003	44.6075	1681
161999	18.7637	1518
161998	12.6962	1236
162001	6.6506	1306
162002	2.6562	854
161997	2.5381	145
161973	1.7035	363
161974	1.6887	281

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.01	gold quality
monocyte	CL:0000576	98.95	gold quality
mononuclear cell	CL:0000842	98.93	gold quality
leukocyte	CL:0000738	98.88	gold quality
colonic epithelium	UBERON:0000397	98.86	gold quality
gall bladder	UBERON:0002110	98.81	gold quality
rectum	UBERON:0001052	98.80	gold quality
mucosa of urinary bladder	UBERON:0001259	98.74	gold quality
islet of Langerhans	UBERON:0000006	98.00	gold quality
pericardium	UBERON:0002407	97.99	gold quality
upper lobe of left lung	UBERON:0008952	97.93	gold quality
vermiform appendix	UBERON:0001154	97.90	gold quality
lower esophagus mucosa	UBERON:0035834	97.88	gold quality
spleen	UBERON:0002106	97.86	gold quality
vena cava	UBERON:0004087	97.84	gold quality
trachea	UBERON:0003126	97.80	gold quality
upper lobe of lung	UBERON:0008948	97.75	gold quality
pancreatic ductal cell	CL:0002079	97.74	gold quality
peripheral nervous system	UBERON:0000010	97.68	gold quality
nerve	UBERON:0001021	97.68	gold quality
tibial nerve	UBERON:0001323	97.68	gold quality
left uterine tube	UBERON:0001303	97.66	gold quality
calcaneal tendon	UBERON:0003701	97.66	gold quality
metanephros cortex	UBERON:0010533	97.60	gold quality
pharyngeal mucosa	UBERON:0000355	97.59	gold quality
pylorus	UBERON:0001166	97.58	gold quality
esophagus mucosa	UBERON:0002469	97.58	gold quality
right lung	UBERON:0002167	97.57	gold quality
caecum	UBERON:0001153	97.56	gold quality
jejunal mucosa	UBERON:0000399	97.53	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	2918.23
E-MTAB-8530	yes	2386.19
E-MTAB-10885	yes	2198.99
E-MTAB-7052	yes	2104.85
E-GEOD-131882	yes	1466.52
E-MTAB-10855	yes	1402.75
E-MTAB-7051	yes	1286.80
E-MTAB-10287	yes	38.58
E-CURD-46	yes	23.80
E-GEOD-81608	yes	8.39
E-GEOD-130148	yes	7.46
E-ENAD-27	yes	6.59
E-MTAB-9801	yes	6.41
E-HCAD-31	yes	6.10
E-CURD-135	no	1024.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, FOXO3, GLI3, HIF1A, KAT7, LILRB4, PPARA

miRNA regulators (miRDB)

51 targeting VMP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-142-5P	99.48	70.92	2416

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 33)

• Endogenously expressed Vmp1 is essentially a cell membrane protein that is involved in cell-cell adhesion, invasion and metastasis. (PMID:17724469)
• VMP1 as a novel autophagy-related membrane protein involved in the initial steps of the mammalian cell autophagic process. (PMID:17940279)
• Vacuole membrane protein 1 is an endoplasmic reticulum protein required for organelle biogenesis, protein secretion, and development (PMID:18550798)
• VMP1 knockdown decreased autophagy and apoptosis in gemcitabine-treated cancer cells (PMID:20299819)
• Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. (PMID:21173155)
• A fusion transcript (RPS6KB1-VMP1) recurrently expressed in 30% of breast cancers is associated with clinical consequences and may indicate genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1. (PMID:21467264)
• VMP1 is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia-induced HCC cell metastasis. (PMID:22144109)
• The expression of VMP1 had significant negative influence on the survival rate of non-small-cell lung cancer patients. (PMID:22333543)
• AKT1-GLI3-VMP1 pathway mediates KRAS oncogene-induced autophagy in cancer cells. (PMID:22535956)
• upregulation of Vmp1 was associated with suppression of growth and pulmonary metastases of HCC. (PMID:22971212)
• The VMP1-Beclin 1 interaction regulates autophagy induction. (PMID:23316280)
• These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents (PMID:23460482)
• in patients with invasive ductal carcinoma of the breast, Vmp1 expression had significant influence on disease-free survival time, with Vmp1-negative patients showing poor prognosis (PMID:23710913)
• In colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death. (PMID:24365149)
• Study indicated that the expression of VMP1 was down-regulated and negatively correlated to the prognosis of colorectal cancer. (PMID:26328607)
• expression of TMEM49 seems to be associated with the apoptosis and metastasis up signaling pathways of ovarian cancer, and suppression of its expression can inhibit cancer cell growth and metastasis (PMID:27023910)
• It has been concluded that VMP1-mediated autophagy cooperated with Kras to promote pancreatic ductal adenocarcinoma initiation. (PMID:27415425)
• We hypothesize that in autophagy VMP1 is required for the correct morphogenesis of the omegasome by regulating MCS at the site of autophagosome formation. (PMID:27861594)
• VMP1 modulates SERCA2 activity to control endoplasmic reticulum contacts for autophagosome formation. (PMID:28890335)
• The results suggest that high VMP1 expression is a potential marker of poor prognosis in HER2 positive BC. Further studies are needed to elucidate how VMP1 could affect pathways supportive of tumorigenesis. (PMID:31442252)
• An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells. (PMID:33318473)
• Essential role for autophagy protein VMP1 in maintaining neuronal homeostasis and preventing axonal degeneration. (PMID:33483473)
• Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. (PMID:34019822)
• VMP1, a novel prognostic biomarker, contributes to glioma development by regulating autophagy. (PMID:34311746)
• Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis. (PMID:35452693)
• VMP1 and TMEM41B are essential for DMV formation during beta-coronavirus infection. (PMID:35536318)
• VMP1 promotes exosome secretion and enhances 5-FU resistance in colon cancer cells. (PMID:35696974)
• Protein expression in exocrine pancreatic diseases. Focus on VMP1 mediated autophagy. (PMID:36088075)
• Ubiquitination Is a Novel Post-Translational Modification of VMP1 in Autophagy of Human Tumor Cells. (PMID:37629161)
• CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer. (PMID:38009649)
• Palmitoylation of vacuole membrane protein 1 promotes small extracellular vesicle secretion via interaction with ALIX and influences intercellular communication. (PMID:38403678)
• Altered vacuole membrane protein 1 (VMP1) expression is associated with increased NLRP3 inflammasome activation and mitochondrial dysfunction. (PMID:38411635)
• Decoding the Versatile Landscape of Autophagic Protein VMP1 in Cancer: A Comprehensive Review across Tissue Types and Regulatory Mechanisms. (PMID:38612567)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	vmp1	ENSDARG00000012450
mus_musculus	Vmp1	ENSMUSG00000018171
rattus_norvegicus	Vmp1	ENSRNOG00000003967
drosophila_melanogaster	CG32087	FBGN0052087
drosophila_melanogaster	Tango5	FBGN0052675
caenorhabditis_elegans		WBGENE00012559

Paralogs (3): PGRMC1 (ENSG00000101856), PGRMC2 (ENSG00000164040), CYB5D2 (ENSG00000167740)

Protein

Protein identifiers

Vacuole membrane protein 1 — Q96GC9 (reviewed: Q96GC9)

Alternative names: Transmembrane protein 49

All UniProt accessions (13): Q96GC9, A0AA34QVJ7, A0AA34QVW5, K7EK01, K7EL46, K7EL74, K7EL93, K7ELS2, K7EM96, K7EMI0, K7EMN6, K7ENU2, K7EPE7

UniProt curated annotations — full annotation on UniProt →

Function. Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly. Regulates ATP2A2 activity to control ER-isolation membrane contacts for autophagosome formation. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required. Modulates ER contacts with lipid droplets, mitochondria and endosomes. Plays an essential role in formation of cell junctions. Upon stress such as bacterial and viral infection, promotes formation of cytoplasmic vacuoles followed by cell death. Involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis. (Microbial infection) Host factor required for infection by all flaviviruses tested such as Zika virus and Yellow fever virus. Probably required post-entry of the virus to facilitate the ER membrane remodeling necessary to form replication organelles.

Subunit / interactions. Interacts with BECN1. Interacts with TJP1. Interacts with TP53INP2. Interacts with TMEM41B. Interacts with ATP2A2, PLN and SLN; competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with ATG2A.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment membrane. Cell membrane. Vacuole membrane. Endoplasmic reticulum membrane.

Domain organisation. The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain. (Microbial infection) VTT domain is required for flavivirus infection.

Similarity. Belongs to the VMP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GC9-1	1	yes
Q96GC9-2	2

RefSeq proteins (10): NP_001316323, NP_001316324, NP_001316325, NP_001316326, NP_001316327, NP_001316328, NP_001316329, NP_001316330, NP_001316331, NP_112200* (*=MANE)

Domains & families (InterPro)

Catalyzed reactions (Rhea), 4 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) (RHEA:38663)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)
• cholesterol(in) = cholesterol(out) (RHEA:39747)

UniProt features (25 total): topological domain 8, transmembrane region 7, region of interest 2, mutagenesis site 2, initiator methionine 1, chain 1, compositionally biased region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GC9-F1	78.64	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
197	decreases interaction with atp2a2.
279	decreases interaction with atp2a2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 329 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOZGIT_ESR1_TARGETS_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, MODULE_128, CHANDRAN_METASTASIS_DN, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_MEMBRANE_DOCKING, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (14): autophagosome assembly (GO:0000045), autophagy (GO:0006914), Golgi organization (GO:0007030), embryo implantation (GO:0007566), autophagosome membrane docking (GO:0016240), cell junction assembly (GO:0034329), lipoprotein transport (GO:0042953), cell-cell adhesion (GO:0098609), organelle localization by membrane tethering (GO:0140056), positive regulation of ATPase-coupled calcium transmembrane transporter activity (GO:1901896), obsolete mitochondrion-endoplasmic reticulum membrane tethering (GO:1990456), lipid transport (GO:0006869), cell adhesion (GO:0007155), plasma membrane phospholipid scrambling (GO:0017121)

GO Molecular Function (2): phospholipid scramblase activity (GO:0017128), protein binding (GO:0005515)

GO Cellular Component (11): phagophore assembly site (GO:0000407), autophagosome membrane (GO:0000421), nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), vacuole (GO:0005773), vacuolar membrane (GO:0005774)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
vacuole	2
bounding membrane of organelle	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
endomembrane system organization	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
autophagosome maturation	1
organelle localization by membrane tethering	1
cellular component assembly	1
cell junction organization	1
protein transport	1
lipoprotein localization	1
cell adhesion	1
membrane docking	1
organelle localization	1
P-type calcium transporter activity	1
positive regulation of ion transmembrane transporter activity	1
positive regulation of ATP-dependent activity	1
regulation of ATPase-coupled calcium transmembrane transporter activity	1
transport	1
lipid localization	1
cellular process	1
plasma membrane organization	1
phospholipid translocation	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VMP1	BECN1	Q14457	993
VMP1	PIK3C3	Q8NEB9	890
VMP1	TMEM41B	Q5BJD5	817
VMP1	WIPI1	Q5MNZ9	799
VMP1	ATG101	Q9BSB4	758
VMP1	ATG13	O75143	750
VMP1	PIK3R4	Q99570	737
VMP1	RB1CC1	Q8TDY2	709
VMP1	ATG14	Q6ZNE5	701
VMP1	AMBRA1	Q9C0C7	693
VMP1	ATG12	O94817	690
VMP1	ATG5	Q9H1Y0	676
VMP1	EI24	O14681	666
VMP1	ATG7	O95352	666
VMP1	EPG5	Q9HCE0	665

IntAct

81 interactions, top by confidence:

A	B	Type	Score
BECN1	PIK3C3	psi-mi:“MI:0914”(association)	0.970
MTOR	RICTOR	psi-mi:“MI:0914”(association)	0.970
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
VMP1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.670
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
MEOX2	VMP1	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	VMP1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	VMP1	psi-mi:“MI:0915”(physical association)	0.560
VMP1	SLC39A9	psi-mi:“MI:0915”(physical association)	0.560
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
CDH13	INSIG1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
VMP1	BECN1	psi-mi:“MI:0915”(physical association)	0.500
VMP1	BECN1	psi-mi:“MI:0914”(association)	0.500
TJP1	VMP1	psi-mi:“MI:0915”(physical association)	0.490
	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DPEP1	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (238): VMP1 (Affinity Capture-Western), VMP1 (Co-localization), VMP1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), VMP1 (Synthetic Lethality), VMP1 (Proximity Label-MS), VMP1 (Proximity Label-MS), VMP1 (Proximity Label-MS), VMP1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), VMP1 (Affinity Capture-MS), VMP1 (Two-hybrid), VMP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3S9V6, A0M8U1, A6NH52, E1BWM5, O35089, P13666, P86050, Q00765, Q0VCK9, Q0X0A5, Q1RLU8, Q29S14, Q2PG42, Q3KNM2, Q3ZC24, Q5BJU5, Q5M7T4, Q5R9I4, Q5R9K4, Q5RE33, Q5T4T1, Q5ZJ41, Q5ZJD7, Q6DD32, Q6GM44, Q6NYF1, Q6P360, Q6PI25, Q7TQ48, Q86TD4, Q8C407, Q8L5Y9, Q8MK44, Q8R1Z9, Q91ZQ0, Q940S0, Q96GC9, Q99K70, Q99KU0, Q9BSR8

Diamond homologs: F4I8Q7, Q0VCK9, Q54NL4, Q5R9K4, Q5XF36, Q68EQ9, Q6INE8, Q6NYY9, Q91ZQ0, Q96GC9, Q99KU0, Q9XWU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

44 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2514 predictions. Top by Δscore:

Variant	Effect	Δscore
17:59707381:T:TA	donor_gain	1.0000
17:59707402:C:A	donor_gain	1.0000
17:59731413:T:A	acceptor_gain	1.0000
17:59731419:A:AG	acceptor_gain	1.0000
17:59731420:G:GG	acceptor_gain	1.0000
17:59731518:CACAG:C	donor_loss	1.0000
17:59731519:ACAG:A	donor_loss	1.0000
17:59731520:CAGG:C	donor_loss	1.0000
17:59731521:AG:A	donor_loss	1.0000
17:59731522:G:GC	donor_loss	1.0000
17:59731524:T:G	donor_loss	1.0000
17:59735336:A:AG	acceptor_gain	1.0000
17:59735337:G:GA	acceptor_gain	1.0000
17:59735426:G:GG	donor_gain	1.0000
17:59735460:G:GT	donor_gain	1.0000
17:59735461:A:T	donor_gain	1.0000
17:59735474:G:GG	donor_gain	1.0000
17:59737451:A:G	acceptor_gain	1.0000
17:59738836:G:GA	acceptor_gain	1.0000
17:59738836:GT:G	acceptor_gain	1.0000
17:59738836:GTAT:G	acceptor_gain	1.0000
17:59764965:TTATA:T	acceptor_loss	1.0000
17:59764966:TATA:T	acceptor_loss	1.0000
17:59764968:TAGG:T	acceptor_loss	1.0000
17:59764969:AG:A	acceptor_gain	1.0000
17:59764970:G:A	acceptor_loss	1.0000
17:59764970:GG:G	acceptor_gain	1.0000
17:59765135:GTGG:G	donor_gain	1.0000
17:59773748:A:AG	acceptor_gain	1.0000
17:59773751:TA:T	acceptor_loss	1.0000

AlphaMissense

2657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59738879:T:A	W116R	1.000
17:59738879:T:C	W116R	1.000
17:59738891:G:A	G120R	1.000
17:59738891:G:C	G120R	1.000
17:59738892:G:A	G120E	1.000
17:59738892:G:T	G120V	1.000
17:59738901:C:T	S123F	1.000
17:59738909:G:A	G126R	1.000
17:59738909:G:C	G126R	1.000
17:59738910:G:A	G126E	1.000
17:59738915:G:A	G128R	1.000
17:59738915:G:C	G128R	1.000
17:59738916:G:A	G128E	1.000
17:59738916:G:T	G128V	1.000
17:59738921:G:A	G130R	1.000
17:59738921:G:C	G130R	1.000
17:59738921:G:T	G130W	1.000
17:59738922:G:A	G130E	1.000
17:59738922:G:T	G130V	1.000
17:59738925:T:C	L131P	1.000
17:59738931:C:T	T133I	1.000
17:59738933:T:C	F134L	1.000
17:59738935:T:A	F134L	1.000
17:59738935:T:G	F134L	1.000
17:59738940:T:A	L136H	1.000
17:59738940:T:C	L136P	1.000
17:59738946:T:C	L138P	1.000
17:59764971:G:C	G139R	1.000
17:59764972:G:A	G139D	1.000
17:59764984:C:A	A143D	1.000

dbSNP variants (sampled 300 via entrez): RS1000046922 (17:59761639 T>C), RS1000082737 (17:59765758 G>A), RS1000098222 (17:59718321 C>CA), RS1000132367 (17:59832746 A>C), RS1000137427 (17:59775909 G>C,T), RS1000143054 (17:59762143 G>A,T), RS1000169339 (17:59791701 T>A,C), RS1000188689 (17:59745137 A>G), RS1000220885 (17:59840566 T>C), RS1000223761 (17:59828074 A>G), RS1000278595 (17:59722136 A>T), RS1000288773 (17:59768709 G>A), RS1000302536 (17:59806287 A>C,G), RS1000314759 (17:59817632 T>A,G), RS1000340524 (17:59832177 A>T)

Disease associations

OMIM: gene MIM:611753 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST001727_1	Lipoprotein-associated phospholipase A2 activity and mass	3.000000e-09
GCST004132_90	Crohn’s disease	1.000000e-06
GCST004604_32	Hematocrit	1.000000e-09
GCST004608_126	Granulocyte percentage of myeloid white cells	5.000000e-15
GCST004609_84	Monocyte percentage of white cells	4.000000e-19
GCST004610_83	White blood cell count	2.000000e-23
GCST004613_58	Sum neutrophil eosinophil counts	5.000000e-18
GCST004614_65	Granulocyte count	3.000000e-18
GCST004615_114	Hemoglobin concentration	1.000000e-09
GCST004618_43	White blood cell count (basophil)	9.000000e-10
GCST004620_100	Sum basophil neutrophil counts	9.000000e-18
GCST004625_246	Monocyte count	2.000000e-30
GCST004626_148	Myeloid white cell count	4.000000e-21
GCST004627_175	Lymphocyte count	5.000000e-09
GCST004629_34	Neutrophil count	1.000000e-17
GCST005531_64	Multiple sclerosis	2.000000e-23
GCST005588_10	Idiopathic dilated cardiomyopathy	4.000000e-06
GCST005995_16	Hemoglobin	3.000000e-08
GCST007096_112	Pulse pressure	3.000000e-08
GCST007097_71	Pulse pressure	3.000000e-06
GCST007576_359	Chronotype	1.000000e-09
GCST008721_5	Chronic lymphocytic leukemia or multiple sclerosis	3.000000e-08
GCST008723_4	Marginal zone lymphoma or multiple sclerosis	2.000000e-08
GCST008972_14	Urate levels	8.000000e-09
GCST009597_320	Multiple sclerosis	4.000000e-31
GCST010083_86	Hemoglobin levels	5.000000e-22
GCST010173_106	Triglyceride levels	2.000000e-09
GCST010244_402	Triglyceride levels	3.000000e-10
GCST012226_802	Waist circumference adjusted for body mass index	4.000000e-08
GCST90000025_602	Appendicular lean mass	1.000000e-11

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004348	hematocrit
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement
EFO:0004530	triglyceride measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066488 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.71	Kd	1931	nM	CHEMBL5653589
5.71	ED50	1931	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149768: Binding affinity to human VMP1 incubated for 45 mins by Kinobead based pull down assay	kd	1.9314	uM

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	5
Benzo(a)pyrene	affects expression, increases expression, affects cotreatment	4
Aflatoxin B1	decreases methylation, increases expression, increases methylation	3
benzo(b)fluoranthene	affects cotreatment, affects expression, increases expression	2
bisphenol A	affects expression, decreases expression	2
trichostatin A	affects expression, increases expression	2
Dactinomycin	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
fluoranthene	increases expression	1
methylparaben	decreases expression	1
nickel chloride	increases expression	1
sulindac sulfide	increases expression	1
1,2,5,6-dibenzanthracene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
fludioxonil	affects cotreatment, decreases expression	1
methyl-beta-cyclodextrin	decreases reaction, increases expression	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
AG 1879	decreases reaction, increases expression	1
N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide	increases expression, decreases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652810	Binding	Binding affinity to human VMP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

19 cell lines: 19 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1092	BT-549	Cancer cell line	Female
CVCL_1259	HCC1954	Cancer cell line	Female
CVCL_4W93	HCC1954-Luc	Cancer cell line	Female
CVCL_5948	11-9-1-4	Cancer cell line	Female
CVCL_B3MM	HCC1954/TDR	Cancer cell line	Female
CVCL_F1N2	HyCyte BT-549 KO-hARTN	Cancer cell line	Female
CVCL_F1N3	HyCyte BT-549 KO-hBAD	Cancer cell line	Female
CVCL_F1N4	HyCyte BT-549 KO-hCD70	Cancer cell line	Female
CVCL_F1N5	HyCyte BT-549 KO-hEOMES	Cancer cell line	Female
CVCL_J245	BT-549-Luc	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.