VSTM4

Summary

VSTM4 (V-set and transmembrane domain containing 4, HGNC:26470) is a protein-coding gene on chromosome 10q11.23, encoding V-set and transmembrane domain-containing protein 4 (Q8IW00). Peptide Lv enhances L-type voltage-gated calcium channel (L-VGCC) currents in retinal photoreceptors.

Predicted to act upstream of or within several processes, including endothelial cell proliferation; retina blood vessel maintenance; and vasculature development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in membrane.

Source: NCBI Gene 196740 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001031746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26470
Approved symbol	VSTM4
Name	V-set and transmembrane domain containing 4
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31737
Ensembl gene	ENSG00000165633
Ensembl biotype	protein_coding
Entrez	196740

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000298454, ENST00000332853, ENST00000476018, ENST00000956395

RefSeq mRNA: 2 — MANE Select: NM_001031746 NM_001031746, NM_144984

CCDS: CCDS31198, CCDS7228

Canonical transcript exons

ENST00000332853 — 8 exons

Exon	Start	End
ENSE00001094853	49107594	49107995
ENSE00001302734	49085955	49086023
ENSE00001305106	49046983	49047044
ENSE00001306265	49064703	49064736
ENSE00001325756	49014236	49019775
ENSE00001326947	49048478	49048584
ENSE00001326984	49077219	49077326
ENSE00003844774	49115431	49115522

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 91.45.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7425 / max 67.1952, expressed in 683 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109322	1.7425	683

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	91.45	gold quality
adrenal cortex	UBERON:0001235	91.17	gold quality
right adrenal gland cortex	UBERON:0035827	91.07	gold quality
left adrenal gland	UBERON:0001234	90.97	gold quality
right adrenal gland	UBERON:0001233	90.86	gold quality
adrenal gland	UBERON:0002369	90.38	gold quality
right lobe of thyroid gland	UBERON:0001119	88.49	gold quality
vena cava	UBERON:0004087	88.19	gold quality
tendon of biceps brachii	UBERON:0008188	88.18	gold quality
left ovary	UBERON:0002119	87.63	gold quality
descending thoracic aorta	UBERON:0002345	87.61	gold quality
left lobe of thyroid gland	UBERON:0001120	87.16	gold quality
thoracic aorta	UBERON:0001515	86.78	gold quality
thyroid gland	UBERON:0002046	86.72	gold quality
right ovary	UBERON:0002118	86.69	gold quality
ascending aorta	UBERON:0001496	86.66	gold quality
aorta	UBERON:0000947	86.40	gold quality
popliteal artery	UBERON:0002250	86.15	gold quality
tibial artery	UBERON:0007610	86.13	gold quality
adrenal tissue	UBERON:0018303	86.12	gold quality
left coronary artery	UBERON:0001626	85.76	gold quality
right coronary artery	UBERON:0001625	85.65	gold quality
coronary artery	UBERON:0001621	85.56	gold quality
ovary	UBERON:0000992	84.79	gold quality
apex of heart	UBERON:0002098	84.47	gold quality
right lung	UBERON:0002167	83.38	gold quality
endocervix	UBERON:0000458	83.15	gold quality
medial globus pallidus	UBERON:0002477	82.76	gold quality
globus pallidus	UBERON:0001875	82.63	gold quality
subthalamic nucleus	UBERON:0001906	82.63	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.22
E-MTAB-5061	yes	11.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting VSTM4, 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-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-1206	99.30	69.32	1016

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vstm4a	ENSDARG00000010154
danio_rerio	vstm4b	ENSDARG00000053186
mus_musculus	Vstm4	ENSMUSG00000050666
rattus_norvegicus	Vstm4	ENSRNOG00000020078

Paralogs (5): PTGFRN (ENSG00000134247), CD101 (ENSG00000134256), IGSF3 (ENSG00000143061), IGSF8 (ENSG00000162729), VSTM2A (ENSG00000170419)

Protein

Protein identifiers

V-set and transmembrane domain-containing protein 4 — Q8IW00 (reviewed: Q8IW00)

All UniProt accessions (1): Q8IW00

UniProt curated annotations — full annotation on UniProt →

Function. Peptide Lv enhances L-type voltage-gated calcium channel (L-VGCC) currents in retinal photoreceptors.

Subcellular location. Secreted Cell membrane.

Post-translational modifications. Proteolytically cleaved to generate a bioactive peptide.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IW00-1	1	yes
Q8IW00-2	2

RefSeq proteins (2): NP_001026916, NP_659421 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051102	IgSF_V-set/TM_domain	Family

Pfam: PF07686

UniProt features (18 total): glycosylation site 4, sequence variant 3, splice variant 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1, peptide 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IW00-F1	75.17	0.43

Functional residue map

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

Disulfide bonds (1): 46–127

Glycosylation sites (4): 144, 25, 41, 89

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MORF_ITGA2, GOBP_CIRCULATORY_SYSTEM_PROCESS, MORF_RAD51L3, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_SPROUTING_ANGIOGENESIS, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_VASODILATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, DOUGLAS_BMI1_TARGETS_UP, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_RETINA_VASCULATURE_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOBP_RETINA_HOMEOSTASIS, CUI_TCF21_TARGETS_2_DN

GO Biological Process (6): endothelial cell proliferation (GO:0001935), sprouting angiogenesis (GO:0002040), vasodilation (GO:0042311), endothelial cell migration (GO:0043542), retina vasculature development in camera-type eye (GO:0061298), retina blood vessel maintenance (GO:0097601)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
epithelial cell proliferation	1
angiogenesis	1
blood vessel diameter maintenance	1
cell migration	1
vasculature development	1
retina development in camera-type eye	1
retina homeostasis	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSTM4	LSAMP	Q13449	497
VSTM4	TMEM273	Q5T292	479
VSTM4	LGALS12	Q96DT0	477
VSTM4	AGAP6	Q5VW22	430
VSTM4	MSANTD4	Q8NCY6	401
VSTM4	KIAA1328	Q86T90	387
VSTM4	ANTXRL	A6NF34	382
VSTM4	ANKRD13C	Q8N6S4	379
VSTM4	LYRM4	Q9HD34	379
VSTM4	C2orf69	Q8N8R5	377
VSTM4	C10orf71	Q711Q0	374
VSTM4	DRGX	A6NNA5	373
VSTM4	PUS10	Q3MIT2	370
VSTM4	FAM25A	B3EWG3	370
VSTM4	G3V325	G3V325	370

IntAct

30 interactions, top by confidence:

A	B	Type	Score
KRTAP1-1	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
VSTM4	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
TGM1	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
STX1A	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
VSTM4	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	VSTM4	psi-mi:“MI:0915”(physical association)	0.560
VSTM4	LBR	psi-mi:“MI:0915”(physical association)	0.400
VSTM4	PPP1CC	psi-mi:“MI:0915”(physical association)	0.370
VSTM4	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	MDFI	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	TGM1	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	STX1A	psi-mi:“MI:0915”(physical association)	0.000
VSTM4	FKBP7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): VSTM4 (Two-hybrid), VSTM4 (Two-hybrid), VSTM4 (Two-hybrid), VSTM4 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP6-3 (Two-hybrid), KRTAP1-3 (Two-hybrid), VSTM4 (Proximity Label-MS), VSTM4 (Affinity Capture-RNA), VSTM4 (Affinity Capture-RNA), VSTM4 (Two-hybrid)

ESM2 similar proteins: A0JM41, A2VD98, A6QQC6, A8MVW5, B0CLX4, B6ZK76, B6ZK77, O60487, O70255, O88324, O88775, O95976, P01832, P03228, P06907, P08920, P08921, P09619, P0C6B7, P0C6N0, P0CW72, P10522, P20938, P21995, P25189, P27573, P37301, P37998, P59823, P59824, P86176, Q01151, Q4VAH7, Q5EAB0, Q5R804, Q640U3, Q6PCB8, Q6WEB5, Q80UL9, Q86XK7

Diamond homologs: Q8IW00, T1NXB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1666 predictions. Top by Δscore:

Variant	Effect	Δscore
10:49019650:C:CT	donor_gain	1.0000
10:49019651:T:TT	donor_gain	1.0000
10:49048472:CCTTA:C	donor_loss	1.0000
10:49048473:CTTA:C	donor_loss	1.0000
10:49048475:TA:T	donor_loss	1.0000
10:49048476:A:C	donor_loss	1.0000
10:49048580:CTGAG:C	acceptor_gain	1.0000
10:49048581:TGAG:T	acceptor_gain	1.0000
10:49048585:C:CC	acceptor_gain	1.0000
10:49077213:TCTTA:T	donor_loss	1.0000
10:49077214:CTTAC:C	donor_loss	1.0000
10:49077215:TTA:T	donor_loss	1.0000
10:49077216:TACC:T	donor_loss	1.0000
10:49077218:C:G	donor_loss	1.0000
10:49077218:CCT:C	donor_gain	1.0000
10:49077322:GAGAT:G	acceptor_gain	1.0000
10:49077324:GAT:G	acceptor_gain	1.0000
10:49077325:AT:A	acceptor_gain	1.0000
10:49077326:TC:T	acceptor_loss	1.0000
10:49077327:C:CA	acceptor_loss	1.0000
10:49077327:C:CC	acceptor_gain	1.0000
10:49077328:T:G	acceptor_loss	1.0000
10:49085479:T:C	donor_gain	1.0000
10:49085949:CTTTA:C	donor_loss	1.0000
10:49085950:TTTA:T	donor_loss	1.0000
10:49085951:TTA:T	donor_loss	1.0000
10:49085952:TACCT:T	donor_loss	1.0000
10:49085953:A:AG	donor_loss	1.0000
10:49085954:C:CT	donor_loss	1.0000
10:49086019:AATGA:A	acceptor_gain	1.0000

AlphaMissense

2061 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:49107867:A:G	W62R	0.999
10:49107867:A:T	W62R	0.999
10:49019675:A:G	I313T	0.998
10:49107634:C:A	W139C	0.998
10:49107634:C:G	W139C	0.998
10:49107670:G:C	C127W	0.998
10:49107671:C:G	C127S	0.998
10:49107671:C:T	C127Y	0.998
10:49107672:A:G	C127R	0.998
10:49107672:A:T	C127S	0.998
10:49107914:C:G	C46S	0.998
10:49107915:A:G	C46R	0.998
10:49107915:A:T	C46S	0.998
10:49077280:G:C	S191R	0.997
10:49077280:G:T	S191R	0.997
10:49077282:T:G	S191R	0.997
10:49107636:A:G	W139R	0.997
10:49107636:A:T	W139R	0.997
10:49107865:C:A	W62C	0.997
10:49107865:C:G	W62C	0.997
10:49107913:G:C	C46W	0.997
10:49107914:C:T	C46Y	0.997
10:49107665:A:T	V129D	0.996
10:49107678:A:C	Y125D	0.996
10:49019675:A:C	I313S	0.995
10:49107920:A:G	L44P	0.995
10:49019738:A:G	L292P	0.993
10:49107662:T:G	Q130P	0.993
10:49107716:A:G	L112P	0.993
10:49019681:G:T	A311D	0.992

dbSNP variants (sampled 300 via entrez): RS1000003490 (10:49092112 G>A), RS1000007301 (10:49051058 C>G,T), RS1000018260 (10:49038485 G>C), RS1000025315 (10:49079114 G>A), RS1000094744 (10:49036813 T>A,C), RS1000137988 (10:49078873 C>T), RS1000168678 (10:49037883 C>G), RS1000208522 (10:49021130 C>G,T), RS1000226375 (10:49085924 G>A), RS1000238088 (10:49014319 T>A,G), RS1000274352 (10:49061489 A>G,T), RS1000282278 (10:49044487 A>G), RS1000299191 (10:49026458 T>C), RS1000322277 (10:49020788 G>C), RS1000352860 (10:49032046 C>A,G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004603_51	Platelet count	4.000000e-16
GCST004607_116	Plateletcrit	3.000000e-19
GCST004610_111	White blood cell count	2.000000e-10
GCST004627_10	Lymphocyte count	2.000000e-18
GCST009196_4	Pericalcarine cortex volume	3.000000e-06
GCST010703_114	Brain morphology (MOSTest)	8.000000e-19
GCST90002385_479	High light scatter reticulocyte count	8.000000e-09
GCST90002386_400	High light scatter reticulocyte percentage of red cells	7.000000e-09
GCST90002388_556	Lymphocyte count	1.000000e-40
GCST90002389_442	Lymphocyte percentage of white cells	4.000000e-11
GCST90002391_250	Mean corpuscular hemoglobin concentration	8.000000e-21
GCST90002393_351	Monocyte count	3.000000e-19
GCST90002397_710	Mean spheric corpuscular volume	4.000000e-29
GCST90002399_94	Neutrophil percentage of white cells	5.000000e-11
GCST90002400_704	Plateletcrit	6.000000e-48
GCST90002402_116	Platelet count	5.000000e-36
GCST90002404_489	Red cell distribution width	3.000000e-11
GCST90002405_259	Reticulocyte count	5.000000e-14
GCST90002406_298	Reticulocyte fraction of red cells	5.000000e-14
GCST90002407_94	White blood cell count	5.000000e-20
GCST90016667_25	Spleen volume	7.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004587	lymphocyte count
EFO:0004346	neuroimaging measurement
EFO:0007986	reticulocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
afimoxifene	affects response to substance	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	1
pentabromodiphenyl ether	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Calcitriol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methotrexate	decreases expression	1
Parathion	increases methylation	1
Progesterone	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Vanadates	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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