VSTM2L

Summary

VSTM2L (V-set and transmembrane domain containing 2 like, HGNC:16096) is a protein-coding gene on chromosome 20q11.23, encoding V-set and transmembrane domain-containing protein 2-like protein (Q96N03).

Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region.

Source: NCBI Gene 128434 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_080607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16096
Approved symbol	VSTM2L
Name	V-set and transmembrane domain containing 2 like
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	dJ1118M15.2
Ensembl gene	ENSG00000132821
Ensembl biotype	protein_coding
OMIM	616537
Entrez	128434

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000373459, ENST00000373461, ENST00000448944, ENST00000869290, ENST00000954389

RefSeq mRNA: 1 — MANE Select: NM_080607 NM_080607

CCDS: CCDS13299

Canonical transcript exons

ENST00000373461 — 4 exons

Exon	Start	End
ENSE00000906849	37931635	37931804
ENSE00000991797	37933539	37933589
ENSE00001802378	37943981	37945350
ENSE00001936006	37903127	37903471

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 95.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9403 / max 1285.5841, expressed in 1002 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184530	11.6536	972
184532	0.6678	209
184531	0.3103	134
184529	0.3087	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	95.53	gold quality
right frontal lobe	UBERON:0002810	95.51	gold quality
prefrontal cortex	UBERON:0000451	95.13	gold quality
cardiac atrium	UBERON:0002081	94.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.62	gold quality
cortical plate	UBERON:0005343	94.54	gold quality
frontal cortex	UBERON:0001870	94.52	gold quality
anterior cingulate cortex	UBERON:0009835	94.45	gold quality
neocortex	UBERON:0001950	93.81	gold quality
cerebral cortex	UBERON:0000956	93.25	gold quality
amygdala	UBERON:0001876	93.15	gold quality
Ammon’s horn	UBERON:0001954	92.45	gold quality
superior frontal gyrus	UBERON:0002661	92.14	gold quality
hypothalamus	UBERON:0001898	91.32	gold quality
temporal lobe	UBERON:0001871	90.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.93	silver quality
forebrain	UBERON:0001890	89.76	gold quality
postcentral gyrus	UBERON:0002581	89.46	gold quality
parietal lobe	UBERON:0001872	88.93	gold quality
primary visual cortex	UBERON:0002436	88.22	gold quality
brain	UBERON:0000955	88.14	gold quality
entorhinal cortex	UBERON:0002728	88.04	gold quality
middle temporal gyrus	UBERON:0002771	87.48	gold quality
bronchial epithelial cell	CL:0002328	87.38	gold quality
putamen	UBERON:0001874	87.15	gold quality
right uterine tube	UBERON:0001302	86.97	gold quality
bronchus	UBERON:0002185	86.85	gold quality
nucleus accumbens	UBERON:0001882	86.67	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	264.79
E-ANND-3	yes	4.61
E-MTAB-5061	no	3.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting VSTM2L, 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-6798-5P	100.00	65.77	699
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-548Q	98.71	65.35	563

Literature-anchored findings (GeneRIF, showing 3)

• VSTM2L is the first example of a secreted antagonist of humanin (HN) and may play a role in the modulation of HN biological function. (PMID:21393573)
• High Expression of VSTM2L Induced Resistance to Chemoradiotherapy in Rectal Cancer through Downstream IL-4 Signaling. (PMID:33506057)
• VSTM2L contributes to anoikis resistance and acts as a novel biomarker for metastasis and clinical outcome in ovarian cancer. (PMID:37030064)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vstm2l	ENSDARG00000098289
mus_musculus	Vstm2l	ENSMUSG00000037843
rattus_norvegicus		ENSRNOG00000085194
drosophila_melanogaster	Bsg	FBGN0261822
caenorhabditis_elegans		WBGENE00021305

Paralogs (3): NPTN (ENSG00000156642), EMB (ENSG00000170571), BSG (ENSG00000172270)

Protein

Protein identifiers

V-set and transmembrane domain-containing protein 2-like protein — Q96N03 (reviewed: Q96N03)

All UniProt accessions (1): Q96N03

Isoforms (3)

UniProt ID	Names	Canonical?
Q96N03-1	1	yes
Q96N03-2	2
Q96N03-3	3

RefSeq proteins (1): NP_542174* (*=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 (12 total): splice variant 4, compositionally biased region 2, signal peptide 1, chain 1, sequence conflict 1, domain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N03-F1	73.98	0.42

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): 62–142

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): RRAGTTGT_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, CACCAGC_MIR138, CCANNAGRKGGC_UNKNOWN, CAGCAGG_MIR370, GOBP_NEURON_APOPTOTIC_PROCESS, TATA_C, AACTTT_UNKNOWN, chr20q11, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MMEF2_Q6, MEISSNER_NPC_HCP_WITH_H3K27ME3, CDC5_01

GO Biological Process (1): negative regulation of neuron apoptotic process (GO:0043524)

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

GO Cellular Component (3): extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSTM2L	ATXN1	P54253	532
VSTM2L	FPR3	P25089	489
VSTM2L	CPNE8	Q86YQ8	476
VSTM2L	ZNF385B	Q569K4	475
VSTM2L	ARHGAP40	Q5TG30	468
VSTM2L	TRIM11	Q96F44	454
VSTM2L	CBLN2	Q8IUK8	447
VSTM2L	RCAN2	Q14206	445
VSTM2L	IGFBP3	P17936	445
VSTM2L	SOWAHA	Q2M3V2	445
VSTM2L	PIERCE1	Q5BN46	443
VSTM2L	GNG4	P50150	437
VSTM2L	KIAA1755	Q5JYT7	431
VSTM2L	CNTN4	Q8IWV2	418
VSTM2L	NR4A2	P43354	409

IntAct

14 interactions, top by confidence:

A	B	Type	Score
ATXN1	VSTM2L	psi-mi:“MI:0915”(physical association)	0.670
VSTM2L	CCM2	psi-mi:“MI:0915”(physical association)	0.570
VSTM2L	KIR2DL5A	psi-mi:“MI:0915”(physical association)	0.400
ATXN1	VSTM2L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): VSTM2L (Two-hybrid), CCM2 (Affinity Capture-Luminescence), VSTM2L (Biochemical Activity), VSTM2L (Affinity Capture-RNA), VSTM2L (Proximity Label-MS), VSTM2L (Two-hybrid)

ESM2 similar proteins: A1XQX1, A4FUY1, A6NFA1, A6NLU5, B1ATG9, C0HL12, D0PRN2, E1BBQ2, E9PUN2, O09112, O14514, O54693, O54951, O60347, O70141, P01346, P07456, P09535, P0DI97, P10764, P16611, P58400, P58401, P97260, Q0IJ12, Q13202, Q14CZ8, Q20FD0, Q28142, Q28143, Q3TZ87, Q3UHD1, Q63373, Q63376, Q640R3, Q6A039, Q6PDS0, Q6ZRP7, Q80UW0, Q86YJ5

Diamond homologs: A6NLU5, Q0IJ12, Q6PDS0, Q8R0A6, Q8TAG5, Q96N03, Q9JME9, A2A8L5, A7MBJ4, O02827, O75962, P10586, P17790, P18572, P23468, P26453, P29294, P35613, P56276, P97300, P97546, Q01974, Q15746, Q23551, Q28740, Q28824, Q61006, Q64487, Q6PDN3, Q865R3, Q8AXY6, Q99PA3, Q9Y639, Q9Z138, O42414, P11799, Q6UXM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

827 predictions. Top by Δscore:

Variant	Effect	Δscore
20:37931632:C:G	acceptor_gain	1.0000
20:37931633:A:AG	acceptor_gain	1.0000
20:37931634:G:GA	acceptor_gain	1.0000
20:37931634:GC:G	acceptor_gain	1.0000
20:37931634:GCC:G	acceptor_gain	1.0000
20:37931634:GCCC:G	acceptor_gain	1.0000
20:37931634:GCCCT:G	acceptor_gain	1.0000
20:37931802:CAGGT:C	donor_loss	1.0000
20:37931805:GTAAT:G	donor_loss	1.0000
20:37931806:T:A	donor_loss	1.0000
20:37903471:GGT:G	donor_loss	0.9900
20:37903472:G:A	donor_loss	0.9900
20:37903472:G:GG	donor_gain	0.9900
20:37903473:T:G	donor_loss	0.9900
20:37931631:A:AG	acceptor_gain	0.9900
20:37933527:C:CA	acceptor_gain	0.9900
20:37933584:A:AG	donor_gain	0.9900
20:37933584:A:G	donor_gain	0.9900
20:37933588:GT:G	donor_gain	0.9900
20:37943976:CCCA:C	acceptor_loss	0.9900
20:37943978:CAGGT:C	acceptor_loss	0.9900
20:37943979:A:AG	acceptor_gain	0.9900
20:37943979:AG:A	acceptor_gain	0.9900
20:37943979:AGGT:A	acceptor_gain	0.9900
20:37943980:G:GA	acceptor_loss	0.9900
20:37943980:G:GG	acceptor_gain	0.9900
20:37943980:GG:G	acceptor_gain	0.9900
20:37943980:GGTG:G	acceptor_gain	0.9900
20:37903474:GAGT:G	donor_loss	0.9800
20:37927480:TGGAG:T	donor_gain	0.9800

AlphaMissense

1316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:37931640:T:C	F43L	1.000
20:37931641:T:C	F43S	1.000
20:37931641:T:G	F43C	1.000
20:37931642:C:A	F43L	1.000
20:37931642:C:G	F43L	1.000
20:37931653:C:A	P47H	1.000
20:37931692:T:C	M60T	1.000
20:37931692:T:G	M60R	1.000
20:37931697:T:A	C62S	1.000
20:37931697:T:C	C62R	1.000
20:37931698:G:A	C62Y	1.000
20:37931698:G:C	C62S	1.000
20:37931698:G:T	C62F	1.000
20:37931699:C:G	C62W	1.000
20:37931703:T:C	F64L	1.000
20:37931704:T:C	F64S	1.000
20:37931704:T:G	F64C	1.000
20:37931705:C:A	F64L	1.000
20:37931705:C:G	F64L	1.000
20:37931734:T:C	L74P	1.000
20:37931740:T:A	I76N	1.000
20:37931740:T:C	I76T	1.000
20:37931740:T:G	I76S	1.000
20:37931743:A:C	Q77P	1.000
20:37931745:T:A	W78R	1.000
20:37931745:T:C	W78R	1.000
20:37931746:G:C	W78S	1.000
20:37931747:G:C	W78C	1.000
20:37931747:G:T	W78C	1.000
20:37931748:T:A	W79R	1.000

dbSNP variants (sampled 300 via entrez): RS1000021314 (20:37930179 T>A,G), RS1000069252 (20:37925238 C>T), RS1000069386 (20:37924918 G>A), RS1000113197 (20:37902669 C>G,T), RS1000166926 (20:37902313 A>G), RS1000255649 (20:37924849 G>A), RS1000340705 (20:37912742 C>T), RS1000364468 (20:37918877 C>A,G), RS1000449186 (20:37918447 G>A), RS1000497583 (20:37929884 G>T), RS1000539998 (20:37940204 C>T), RS1000558319 (20:37919663 C>G,T), RS1000580808 (20:37925892 A>G), RS1000605131 (20:37939121 T>A), RS1000632853 (20:37918193 C>T)

Disease associations

OMIM: gene MIM:616537 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010322_4	Levodopa wearing off effect (time symptoms uncontrolled) in Parkinson’s disease (response to zonisamide)	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010747	response to levodopa
EFO:0010749	motor function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	3
Air Pollutants	decreases expression, increases abundance	2
Estradiol	increases expression, affects cotreatment	2
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
lead acetate	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	decreases expression	1
tobacco tar	decreases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	increases expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Cadmium	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cannabinoids	affects methylation, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression, increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, increases abundance	1
Testosterone	affects cotreatment, increases expression	1
Triclosan	decreases expression	1
Tunicamycin	decreases expression	1

Clinical trials (associated diseases)

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