VSTM5

Summary

VSTM5 (V-set and transmembrane domain containing 5, HGNC:34443) is a protein-coding gene on chromosome 11q21, encoding V-set and transmembrane domain-containing protein 5 (A8MXK1). Cell adhesion-like membrane protein of the central nervous system (CNS) which modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics.

Predicted to be involved in several processes, including filopodium assembly; positive regulation of excitatory synapse assembly; and protein homooligomerization. Predicted to be located in membrane. Predicted to be active in axon; dendrite; and plasma membrane.

Source: NCBI Gene 387804 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001144871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34443
Approved symbol	VSTM5
Name	V-set and transmembrane domain containing 5
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	LOC387804
Ensembl gene	ENSG00000214376
Ensembl biotype	protein_coding
OMIM	621118
Entrez	387804

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000398221, ENST00000409977, ENST00000414919, ENST00000960694

RefSeq mRNA: 1 — MANE Select: NM_001144871 NM_001144871

CCDS: CCDS44709

Canonical transcript exons

ENST00000409977 — 4 exons

Exon	Start	End
ENSE00001532182	93820743	93820883
ENSE00001532183	93820997	93821323
ENSE00001577951	93850412	93850618
ENSE00001582531	93818232	93820612

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 90.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2069 / max 21.0693, expressed in 93 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121839	0.2069	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	90.14	gold quality
quadriceps femoris	UBERON:0001377	85.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.48	gold quality
thymus	UBERON:0002370	80.01	silver quality
placenta	UBERON:0001987	76.53	gold quality
prefrontal cortex	UBERON:0000451	73.54	gold quality
superior frontal gyrus	UBERON:0002661	73.42	gold quality
primary visual cortex	UBERON:0002436	72.51	gold quality
hypothalamus	UBERON:0001898	72.02	gold quality
frontal cortex	UBERON:0001870	71.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.54	gold quality
cerebral cortex	UBERON:0000956	69.24	gold quality
right frontal lobe	UBERON:0002810	69.16	gold quality
anterior cingulate cortex	UBERON:0009835	66.61	gold quality
rectum	UBERON:0001052	65.79	gold quality
stromal cell of endometrium	CL:0002255	63.83	gold quality
Ammon’s horn	UBERON:0001954	62.77	gold quality
substantia nigra	UBERON:0002038	62.68	gold quality
smooth muscle tissue	UBERON:0001135	62.57	gold quality
brain	UBERON:0000955	62.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.19	gold quality
temporal lobe	UBERON:0001871	62.00	gold quality
amygdala	UBERON:0001876	61.84	gold quality
transverse colon	UBERON:0001157	60.80	gold quality
cortical plate	UBERON:0005343	60.69	gold quality
colon	UBERON:0001155	60.43	gold quality
body of stomach	UBERON:0001161	59.87	gold quality
colonic epithelium	UBERON:0000397	59.67	gold quality
intestine	UBERON:0000160	59.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.93

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkeyp-97a10.3	ENSDARG00000104656
mus_musculus	Vstm5	ENSMUSG00000031937
rattus_norvegicus	Vstm5	ENSRNOG00000010480

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM6 (ENSG00000086548), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), PSG5 (ENSG00000204941), CEACAM18 (ENSG00000213822), CEACAM16 (ENSG00000213892), PSG3 (ENSG00000221826), PSG7 (ENSG00000221878), PSG1 (ENSG00000231924), PSG2 (ENSG00000242221), PSG11 (ENSG00000243130), PSG4 (ENSG00000243137), CEACAM20 (ENSG00000273777)

Protein

Protein identifiers

V-set and transmembrane domain-containing protein 5 — A8MXK1 (reviewed: A8MXK1)

All UniProt accessions (2): A8MXK1, H0Y3Q1

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion-like membrane protein of the central nervous system (CNS) which modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Involved in the formation of neuronal dendrites and protrusions including dendritic filopodia. In synaptogenesis, regulates synapse formation by altering dendritic spine morphology and actin distribution. Promotes formation of unstable neuronal spines such as thin and branched types. Regulates neuronal morphogenesis and migration during cortical development in the brain.

Subunit / interactions. Can homooligomerize through cis interactions within the same cell membrane.

Subcellular location. Cell membrane. Cell projection. Dendrite. Axon.

Post-translational modifications. N-glycosylated.

RefSeq proteins (1): NP_001138343* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015631	CD2/SLAM_rcpt	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

UniProt features (8 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MXK1-F1	88.18	0.64

Functional residue map

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

Glycosylation sites (1): 102

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_CELL_JUNCTION_ASSEMBLY

GO Biological Process (5): immune response (GO:0006955), ventral spinal cord development (GO:0021517), filopodium assembly (GO:0046847), protein homooligomerization (GO:0051260), positive regulation of excitatory synapse assembly (GO:1904891)

GO Molecular Function (0):

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
neuron projection	2
immune system process	1
response to stimulus	1
spinal cord development	1
anatomical structure development	1
plasma membrane bounded cell projection assembly	1
protein complex oligomerization	1
positive regulation of synapse assembly	1
excitatory synapse assembly	1
regulation of excitatory synapse assembly	1
membrane	1
cell periphery	1
dendritic tree	1

Protein interactions and networks

STRING

172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VSTM5	BKGD	Q9H0W9	585
VSTM5	SMCO4	Q9NRQ5	564
VSTM5	GPR176	Q14439	546
VSTM5	VWA5B1	Q5TIE3	542
VSTM5	GPR75	O95800	530
VSTM5	MED17	Q9NVC6	527
VSTM5	GALR1	P47211	458
VSTM5	HEPHL1	Q6MZM0	450
VSTM5	MTMR12	Q9C0I1	421
VSTM5	DHRS7C	A6NNS2	420
VSTM5	ANKRD55	Q3KP44	408
VSTM5	KCNIP4	Q6PIL6	386
VSTM5	LRRN2	O75325	380
VSTM5	LARGE2	Q8N3Y3	366
VSTM5	TM4SF5	O14894	348

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2AIG8, A5D7H1, A6H7A0, A6NFX1, A6NJW4, A8MUP2, A8MXK1, B0BMW8, O35393, O54804, O73884, P01135, P35790, P52875, P57791, Q00961, Q01098, Q01134, Q06922, Q08DW9, Q0P5M9, Q0VDI3, Q14728, Q14957, Q15768, Q2M1K6, Q3UGX3, Q4R7M4, Q4V899, Q5E9H2, Q5M7U7, Q5R6I6, Q5RCI5, Q5ZI20, Q7TPB4, Q8BZH0, Q8IVW8, Q8N431, Q8NBA8, Q8R2R5

Diamond homologs: A8MXK1, Q5M7U7, Q9D806, Q29RR6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

510 predictions. Top by Δscore:

Variant	Effect	Δscore
11:93850408:TTACT:T	donor_loss	1.0000
11:93850410:A:AC	donor_gain	1.0000
11:93850411:C:CC	donor_gain	1.0000
11:93850411:CT:C	donor_gain	1.0000
11:93850411:CTCTG:C	donor_gain	1.0000
11:93820613:C:CC	acceptor_gain	0.9900
11:93820991:TCTTA:T	donor_loss	0.9900
11:93820992:CTTA:C	donor_loss	0.9900
11:93820993:TTA:T	donor_loss	0.9900
11:93820994:TA:T	donor_loss	0.9900
11:93820995:A:AC	donor_gain	0.9900
11:93820995:ACC:A	donor_loss	0.9900
11:93820996:C:CC	donor_gain	0.9900
11:93820996:C:CT	donor_loss	0.9900
11:93850410:ACT:A	donor_gain	0.9900
11:93850411:CTC:C	donor_gain	0.9900
11:93850411:CTCT:C	donor_gain	0.9900
11:93820609:CTTT:C	acceptor_gain	0.9800
11:93820610:TTT:T	acceptor_gain	0.9800
11:93820611:TTC:T	acceptor_loss	0.9800
11:93820612:TC:T	acceptor_loss	0.9800
11:93820613:CT:C	acceptor_loss	0.9800
11:93820614:T:A	acceptor_loss	0.9800
11:93820882:CT:C	acceptor_gain	0.9800
11:93820884:C:CC	acceptor_gain	0.9800
11:93820897:G:C	acceptor_gain	0.9800
11:93820990:GTCTT:G	donor_loss	0.9800
11:93820883:TC:T	acceptor_loss	0.9700
11:93820884:CT:C	acceptor_loss	0.9700
11:93820885:T:C	acceptor_loss	0.9700

AlphaMissense

1300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:93821216:A:G	W67R	0.997
11:93821216:A:T	W67R	0.997
11:93821105:A:G	S104P	0.994
11:93821214:C:A	W67C	0.992
11:93821214:C:G	W67C	0.992
11:93821174:A:G	W81R	0.990
11:93821174:A:T	W81R	0.990
11:93821107:C:T	G103D	0.988
11:93821172:C:A	W81C	0.988
11:93821172:C:G	W81C	0.988
11:93821215:C:G	W67S	0.985
11:93820807:G:C	S165R	0.983
11:93820807:G:T	S165R	0.983
11:93820809:T:G	S165R	0.983
11:93821107:C:A	G103V	0.983
11:93821108:C:G	G103R	0.979
11:93821063:A:C	Y118D	0.978
11:93821101:A:T	I105N	0.977
11:93821251:A:T	V55D	0.975
11:93821095:A:G	L107P	0.973
11:93821109:G:C	N102K	0.972
11:93821109:G:T	N102K	0.972
11:93821074:T:A	D114V	0.971
11:93821002:A:T	V138D	0.970
11:93821074:T:G	D114A	0.969
11:93821104:G:A	S104F	0.969
11:93821115:A:C	F100L	0.969
11:93821115:A:T	F100L	0.969
11:93821117:A:G	F100L	0.969
11:93821075:C:G	D114H	0.968

dbSNP variants (sampled 300 via entrez): RS1000120295 (11:93850833 A>T), RS1000187537 (11:93849362 G>A), RS1000270798 (11:93826406 CT>C,CTT), RS1000316950 (11:93838794 T>C), RS1000319998 (11:93843134 C>G,T), RS1000361346 (11:93820394 C>A,T), RS1000417555 (11:93848680 T>C,G), RS1000423650 (11:93850560 C>G,T), RS1000424132 (11:93832939 G>C), RS1000704146 (11:93843354 G>A,T), RS1000781902 (11:93837921 A>G), RS1000910053 (11:93818762 C>T), RS1001025652 (11:93849275 G>A), RS1001122621 (11:93826612 G>A), RS1001126391 (11:93825374 T>C,G)

Disease associations

OMIM: gene MIM:621118 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
Benzo(a)pyrene	affects methylation	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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