TSPAN3

Summary

TSPAN3 (tetraspanin 3, HGNC:17752) is a protein-coding gene on chromosome 15q24.3, encoding Tetraspanin-3 (O60637). Regulates the proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. The use of alternate polyadenylation sites has been found for this gene. Multiple alternative transcripts encoding different isoforms have been described.

Source: NCBI Gene 10099 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_005724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17752
Approved symbol	TSPAN3
Name	tetraspanin 3
Location	15q24.3
Locus type	gene with protein product
Status	Approved
Aliases	TM4-A, TSPAN-3
Ensembl gene	ENSG00000140391
Ensembl biotype	protein_coding
OMIM	613134
Entrez	10099

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000267970, ENST00000346495, ENST00000424443, ENST00000558394, ENST00000558745, ENST00000559373, ENST00000559494, ENST00000560514, ENST00000560715, ENST00000561277

RefSeq mRNA: 3 — MANE Select: NM_005724 NM_001168412, NM_005724, NM_198902

CCDS: CCDS10292, CCDS10293, CCDS53963

Canonical transcript exons

ENST00000267970 — 7 exons

Exon	Start	End
ENSE00002551071	77041404	77046927
ENSE00003545790	77056064	77056255
ENSE00003580876	77052777	77052929
ENSE00003582030	77055789	77055863
ENSE00003597922	77052385	77052468
ENSE00003604122	77070892	77071109
ENSE00003616728	77054178	77054279

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.6546 / max 660.8922, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151033	51.7974	1817
151031	31.2680	1793
151030	4.4123	1403
151032	3.2880	1343
151028	1.5881	753
151034	0.9151	589
151035	0.3856	176

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.61	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.56	gold quality
colonic mucosa	UBERON:0000317	99.52	gold quality
epithelium of bronchus	UBERON:0002031	99.51	gold quality
bronchus	UBERON:0002185	99.47	gold quality
ventricular zone	UBERON:0003053	99.43	gold quality
rectum	UBERON:0001052	99.41	gold quality
corpus epididymis	UBERON:0004359	99.38	gold quality
type B pancreatic cell	CL:0000169	99.33	gold quality
palpebral conjunctiva	UBERON:0001812	99.30	gold quality
caput epididymis	UBERON:0004358	99.30	gold quality
eye	UBERON:0000970	99.28	gold quality
right uterine tube	UBERON:0001302	99.28	gold quality
lateral globus pallidus	UBERON:0002476	99.26	gold quality
jejunal mucosa	UBERON:0000399	99.25	gold quality
mucosa of transverse colon	UBERON:0004991	99.25	gold quality
pigmented layer of retina	UBERON:0001782	99.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.22	gold quality
retina	UBERON:0000966	99.21	gold quality
duodenum	UBERON:0002114	99.18	gold quality
ganglionic eminence	UBERON:0004023	99.18	gold quality
hypothalamus	UBERON:0001898	99.15	gold quality
gall bladder	UBERON:0002110	99.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.11	gold quality
amygdala	UBERON:0001876	99.10	gold quality
seminal vesicle	UBERON:0000998	99.08	gold quality
middle temporal gyrus	UBERON:0002771	99.08	gold quality
caudate nucleus	UBERON:0001873	99.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.07	gold quality
nucleus accumbens	UBERON:0001882	99.06	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	74.99
E-CURD-114	yes	48.14
E-HCAD-10	yes	38.10
E-GEOD-125970	yes	28.24
E-CURD-122	yes	24.97
E-MTAB-8410	yes	23.36
E-HCAD-13	yes	14.36
E-MTAB-6678	yes	4.04
E-MTAB-8498	no	1377.91
E-MTAB-9388	no	11.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting TSPAN3, 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-4673	100.00	66.64	1490
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-183-3P	99.41	69.41	1598

Literature-anchored findings (GeneRIF, showing 6)

• Tspan3 is an important regulator of aggressive leukemias. (PMID:26212080)
• Studies indicate that tetraspanin 3 has a critical role in acute myeloid leukemia. (PMID:26930362)
• Tspan3 is a central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein. (PMID:27818272)
• study concluded that miR-139-5p suppressed the leukemogenesis in acute myeloid leukemia (AML) cells by targeting Tspan3 through inactivation of the PI3K/Akt pathway, providing a better understanding of AML progression. (PMID:30367526)
• High TSPAN3 expression is associated with progression and chemoresistance in acute myeloid leukemia. (PMID:31837329)
• Tetraspanin 3 promotes NSCLC cell proliferation via regulation of beta1 integrin intracellular recycling. (PMID:39333841)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspan3a	ENSDARG00000034753
danio_rerio	tspan3b	ENSDARG00000053559
mus_musculus	Tspan3	ENSMUSG00000032324
rattus_norvegicus	Tspan3	ENSRNOG00000016474

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), PRPH2 (ENSG00000112619), UPK1B (ENSG00000114638), TSPAN1 (ENSG00000117472), TSPAN8 (ENSG00000127324), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Tetraspanin-3 — O60637 (reviewed: O60637)

Alternative names: Tetraspanin TM4-A, Transmembrane 4 superfamily member 8

All UniProt accessions (3): O60637, H0YKJ9, H0YMH8

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.

Subunit / interactions. Interacts with claudin-11/CLDN11 and integrins.

Subcellular location. Membrane.

Similarity. Belongs to the tetraspanin (TM4SF) family.

Isoforms (3)

UniProt ID	Names	Canonical?
O60637-1	1	yes
O60637-2	2
O60637-3	3

RefSeq proteins (3): NP_001161884, NP_005715, NP_944492 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000301	Tetraspanin_animals	Family
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018499	Tetraspanin/Peripherin	Family
IPR018503	Tetraspanin_CS	Conserved_site

Pfam: PF00335

UniProt features (18 total): topological domain 5, glycosylation site 4, transmembrane region 4, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60637-F1	86.66	0.57

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 (4): 127, 152, 167, 183

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 224 (showing top): MODULE_52, ZHAN_LATE_DIFFERENTIATION_GENES_UP, BECKER_TAMOXIFEN_RESISTANCE_UP, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, WOO_LIVER_CANCER_RECURRENCE_UP, MARTINEZ_RB1_TARGETS_DN, MODULE_206, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, ZHOU_TNF_SIGNALING_4HR, MODULE_6, MODULE_18, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, MARTINEZ_RB1_AND_TP53_TARGETS_UP, MODULE_223, OSMAN_BLADDER_CANCER_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN3	ITGB1	P05556	739
TSPAN3	CD82	P27701	607
TSPAN3	TPM3	P06753	591
TSPAN3	CLDN11	O75508	532
TSPAN3	RCN2	Q14257	506
TSPAN3	CD81	P18582	481
TSPAN3	TSPAN33	Q86UF1	459
TSPAN3	SCAPER	Q9BY12	432
TSPAN3	TSPAN32	Q96QS1	428
TSPAN3	TSPAN7	P41732	421
TSPAN3	PTGFRN	Q9P2B2	405
TSPAN3	G2E3	Q7L622	391
TSPAN3	DIP2C	Q9Y2E4	391
TSPAN3	GHITM	Q9H3K2	383
TSPAN3	TJP2	Q9UDY2	378

IntAct

74 interactions, top by confidence:

A	B	Type	Score
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
GPR141	STXBP3	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
TRHDE	MAN1A2	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
TSPAN3	DRD2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN3	RXFP4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (174): TSPAN3 (Affinity Capture-MS), NDFIP2 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NOTCH3 (Affinity Capture-MS), CDC6 (Affinity Capture-MS), GABARAP (Affinity Capture-MS), STX6 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), SDCBP (Affinity Capture-MS), CD320 (Affinity Capture-MS), KDSR (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), EPHA4 (Affinity Capture-MS), MAP1LC3B2 (Affinity Capture-MS), RNF149 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2B5N2, A0A8V0ZLT4, A1L157, O00322, O60637, O75841, P11049, P19075, P21926, P30409, P30413, P30932, P31053, P38572, P38573, P40239, P40240, P40241, Q0D289, Q2KHY8, Q2MJQ7, Q3SZR9, Q4R4Z3, Q4R7W6, Q566D0, Q568Y5, Q58CY8, Q5RDV7, Q5RE11, Q5RH71, Q61470, Q6AYR9, Q6GQF5, Q6P0C6, Q6ZUX7, Q80WR1, Q8WMQ3, Q91Y55, Q925N4, Q96FX8

Diamond homologs: O35566, O43657, O60637, O70401, O97703, P35762, P41732, P48509, P60033, P60034, P61170, P61171, Q32KU6, Q3SZR9, Q3ZCD0, Q5RAS5, Q5RE11, Q62283, Q62745, Q7YQK9, Q7YQL0, Q9N0J9, Q9QY33, Q9QZA6, Q9XSK2, O95859, P08962, P11049, P28648, P30932, P40239, P40240, P40241, P41731, Q28709, Q29RH7, Q3SYV5, Q569A2, Q58DM3, Q5R8B5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	6	11.4×	3e-03
GPCR ligand binding	6	9.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
phospholipase C-activating G protein-coupled receptor signaling pathway	6	12.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

976 predictions. Top by Δscore:

Variant	Effect	Δscore
15:77052382:TA:T	donor_gain	1.0000
15:77052383:ACCTG:A	donor_loss	1.0000
15:77052384:CCTG:C	donor_loss	1.0000
15:77052464:CACCC:C	acceptor_gain	1.0000
15:77052466:CCC:C	acceptor_gain	1.0000
15:77052467:CC:C	acceptor_gain	1.0000
15:77052467:CCC:C	acceptor_gain	1.0000
15:77052467:CCCTG:C	acceptor_loss	1.0000
15:77052468:CC:C	acceptor_gain	1.0000
15:77052469:C:CA	acceptor_loss	1.0000
15:77052469:C:CC	acceptor_gain	1.0000
15:77052470:T:C	acceptor_loss	1.0000
15:77052773:TCACC:T	donor_loss	1.0000
15:77052774:CACCT:C	donor_loss	1.0000
15:77052775:A:AC	donor_gain	1.0000
15:77052775:AC:A	donor_gain	1.0000
15:77052775:ACCT:A	donor_gain	1.0000
15:77052776:C:CA	donor_gain	1.0000
15:77052776:C:G	donor_loss	1.0000
15:77052776:CC:C	donor_gain	1.0000
15:77052776:CCT:C	donor_gain	1.0000
15:77052776:CCTC:C	donor_gain	1.0000
15:77052925:TGCAG:T	acceptor_gain	1.0000
15:77052926:GCAG:G	acceptor_gain	1.0000
15:77052927:CAG:C	acceptor_gain	1.0000
15:77052927:CAGC:C	acceptor_gain	1.0000
15:77052928:AG:A	acceptor_gain	1.0000
15:77052930:C:CC	acceptor_gain	1.0000
15:77052930:CTAA:C	acceptor_loss	1.0000
15:77054172:GCTCA:G	donor_loss	1.0000

AlphaMissense

1650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:77052894:C:A	W156C	1.000
15:77052894:C:G	W156C	1.000
15:77052879:C:A	W161C	0.999
15:77052879:C:G	W161C	0.999
15:77052896:A:G	W156R	0.999
15:77052896:A:T	W156R	0.999
15:77052916:C:A	G149V	0.999
15:77052916:C:T	G149E	0.999
15:77052921:A:C	C147W	0.999
15:77052922:C:G	C147S	0.999
15:77052923:A:T	C147S	0.999
15:77052464:C:G	C197S	0.998
15:77052464:C:T	C197Y	0.998
15:77052465:A:T	C197S	0.998
15:77052468:C:A	G196W	0.998
15:77052841:C:G	C174S	0.998
15:77052841:C:T	C174Y	0.998
15:77052842:A:G	C174R	0.998
15:77052842:A:T	C174S	0.998
15:77052895:C:G	W156S	0.998
15:77052919:C:G	C148S	0.998
15:77052919:C:T	C148Y	0.998
15:77052920:A:T	C148S	0.998
15:77052922:C:T	C147Y	0.998
15:77052923:A:G	C147R	0.998
15:77056117:C:G	G68R	0.998
15:77056117:C:T	G68R	0.998
15:77056138:C:G	G61R	0.998
15:77056138:C:T	G61R	0.998
15:77056228:C:G	G31R	0.998

dbSNP variants (sampled 300 via entrez): RS1000077993 (15:77047527 T>G), RS1000132806 (15:77069634 C>T), RS1000152616 (15:77047754 T>C), RS1000237240 (15:77063478 G>A), RS1000391140 (15:77059715 T>C), RS1000423588 (15:77041810 C>T), RS1000441629 (15:77046238 G>A,T), RS1000615574 (15:77057939 T>C,G), RS1000694385 (15:77070584 G>GGA,GGC,GGT), RS1000701385 (15:77069421 T>C), RS1000726512 (15:77070614 G>A), RS1000799547 (15:77063758 T>C), RS1000955334 (15:77055233 A>G), RS1000995163 (15:77044739 C>T), RS1001023949 (15:77042790 A>G)

Disease associations

OMIM: gene MIM:613134 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012227_520	Hip circumference adjusted for BMI	4.000000e-11
GCST90020028_1750	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Clozapine	decreases expression, increases expression	2
Quercetin	decreases expression, increases phosphorylation	2
Rotenone	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
fenpyroximate	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	decreases expression	1
Antimycin A	decreases expression	1
Aspirin	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Benztropine	affects cotreatment, increases expression	1
Cisplatin	increases expression	1
Cuprizone	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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