TSPAN17

Summary

TSPAN17 (tetraspanin 17, HGNC:13594) is a protein-coding gene on chromosome 5q35.2, encoding Tetraspanin-17 (Q96FV3). Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10.

This gene encodes a member of the transmembrane 4 superfamily. It is characterized by four tetraspanin transmembrane segments. The function of this gene has not yet been determined.

Source: NCBI Gene 26262 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_130465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13594
Approved symbol	TSPAN17
Name	tetraspanin 17
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FBX23
Ensembl gene	ENSG00000048140
Ensembl biotype	protein_coding
OMIM	620446
Entrez	26262

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 24 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000298564, ENST00000310032, ENST00000503030, ENST00000503045, ENST00000504168, ENST00000507471, ENST00000508164, ENST00000514705, ENST00000515708, ENST00000860608, ENST00000860609, ENST00000860610, ENST00000860611, ENST00000860612, ENST00000860613, ENST00000860614, ENST00000917608, ENST00000917609, ENST00000917610, ENST00000917611, ENST00000917612, ENST00000917613, ENST00000917614, ENST00000917615, ENST00000956721, ENST00000956722

RefSeq mRNA: 5 — MANE Select: NM_130465 NM_001006616, NM_001366491, NM_001366492, NM_012171, NM_130465

CCDS: CCDS34298, CCDS47346, CCDS54952

Canonical transcript exons

ENST00000508164 — 9 exons

Exon	Start	End
ENSE00001219135	176654895	176655020
ENSE00001716853	176647484	176647702
ENSE00002036859	176657518	176659051
ENSE00003484462	176652743	176652913
ENSE00003494752	176651616	176651666
ENSE00003517507	176656700	176656816
ENSE00003518006	176651754	176651900
ENSE00003667839	176656078	176656125
ENSE00003785372	176656895	176656956

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 92.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2253 / max 253.2741, expressed in 1800 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60432	20.9534	1799
60431	1.2719	949

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	92.84	gold quality
right adrenal gland cortex	UBERON:0035827	92.77	gold quality
pancreatic ductal cell	CL:0002079	92.38	gold quality
left adrenal gland	UBERON:0001234	92.34	gold quality
left adrenal gland cortex	UBERON:0035825	92.24	gold quality
adrenal cortex	UBERON:0001235	92.12	gold quality
cerebellar vermis	UBERON:0004720	91.49	gold quality
adrenal gland	UBERON:0002369	91.45	gold quality
granulocyte	CL:0000094	91.24	gold quality
upper arm skin	UBERON:0004263	90.98	silver quality
ileal mucosa	UBERON:0000331	90.89	gold quality
apex of heart	UBERON:0002098	90.73	gold quality
gastrocnemius	UBERON:0001388	90.65	gold quality
stromal cell of endometrium	CL:0002255	90.64	gold quality
tibialis anterior	UBERON:0001385	90.38	silver quality
muscle of leg	UBERON:0001383	90.12	gold quality
lower esophagus mucosa	UBERON:0035834	89.93	gold quality
prefrontal cortex	UBERON:0000451	89.67	gold quality
nasal cavity epithelium	UBERON:0005384	89.62	silver quality
left ventricle myocardium	UBERON:0006566	89.49	silver quality
mucosa of transverse colon	UBERON:0004991	89.32	gold quality
adrenal tissue	UBERON:0018303	89.32	gold quality
right frontal lobe	UBERON:0002810	89.06	gold quality
heart left ventricle	UBERON:0002084	88.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.76	gold quality
cardiac ventricle	UBERON:0002082	88.60	gold quality
adenohypophysis	UBERON:0002196	88.52	gold quality
anterior cingulate cortex	UBERON:0009835	88.40	gold quality
kidney epithelium	UBERON:0004819	88.35	silver quality
metanephros cortex	UBERON:0010533	88.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting TSPAN17, 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-1184	99.99	68.19	1458
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-378A-3P	98.43	66.10	548

Literature-anchored findings (GeneRIF, showing 2)

• Endothelial Tspan5- and Tspan17-ADAM10 complexes may regulate inflammation by maintaining normal VE-cadherin expression and promoting T lymphocyte transmigration. (PMID:28600292)
• Data suggested that increased miR378a3p and decreased TSPAN17 levels were associated with improved survival in glioblastoma multiforme (GBM). Additionally, high levels of TSPAN17 were linked to the poor prognosis of patients with GBM aged 5060, larger tumor sizes and an advanced World Health Organization stage. TSPAN17 was identified and confirmed as a direct target of miR378a. (PMID:31432186)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspan17	ENSDARG00000114067
mus_musculus	Tspan17	ENSMUSG00000025875
rattus_norvegicus	Tspan17	ENSRNOG00000018122

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), 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), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Tetraspanin-17 — Q96FV3 (reviewed: Q96FV3)

Alternative names: F-box only protein 23, Tetraspan protein SB134, Transmembrane 4 superfamily member 17

All UniProt accessions (6): Q96FV3, D6RBW9, D6RDX8, D6RI03, H0Y9A5, J3KNG2

UniProt curated annotations — full annotation on UniProt →

Function. Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10. This interaction is required for ADAM10 exit from the endoplasmic reticulum and for enzymatic maturation and trafficking to the cell surface as well as substrate specificity. Different TspanC8/ADAM10 complexes have distinct substrates. Seems to regulate VE-cadherin expression in endothelial cells probably through interaction with ADAM10, promoting leukocyte transmigration.

Subunit / interactions. Interacts with ADAM10; the interaction influences ADAM10 substrate specificity, endocytosis and turnover.

Subcellular location. Cell membrane.

Similarity. Belongs to the tetraspanin (TM4SF) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96FV3-1	1	yes
Q96FV3-3	2
Q96FV3-2	3
Q96FV3-4	4

RefSeq proteins (5): NP_001006617, NP_001353420, NP_001353421, NP_036303, NP_569732* (*=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 (23 total): topological domain 5, splice variant 5, disulfide bond 4, transmembrane region 4, glycosylation site 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FV3-F1	88.48	0.72

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 (4): 155–223, 156–188, 172–182, 189–202

Glycosylation sites (2): 51, 171

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GGGTGGRR_PAX4_03, CATRRAGC_UNKNOWN, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, AML_Q6, HFH8_01, TCF11_01, FOXJ2_01, HFH4_01, GOBP_REGULATION_OF_MEMBRANE_PROTEIN_ECTODOMAIN_PROTEOLYSIS, HFH3_01, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (3): intracellular protein localization (GO:0008104), regulation of membrane protein ectodomain proteolysis (GO:0051043), establishment of protein localization to organelle (GO:0072594)

GO Molecular Function (1): enzyme binding (GO:0019899)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
membrane protein ectodomain proteolysis	1
regulation of proteolysis	1
regulation of protein catabolic process	1
establishment of protein localization	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN17	ADAM10	O14672	759
TSPAN17	TSPAN31	Q12999	666
TSPAN17	TSPAN13	O95857	578
TSPAN17	TSPAN12	O95859	493
TSPAN17	CSNK1A1	P48729	491
TSPAN17	TSPAN16	Q9UKR8	392
TSPAN17	ZNF727	A8MUV8	380
TSPAN17	CFAP68	Q9H5F2	370
TSPAN17	SCG5	P01164	363
TSPAN17	TSPAN32	Q96QS1	349
TSPAN17	TSPAN1	O60635	338
TSPAN17	ADAM17	P78536	338
TSPAN17	CDH17	Q12864	321
TSPAN17	FBXO34	Q9NWN3	318
TSPAN17	FAM43B	Q6ZT52	317

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ADAM10	TSPAN17	psi-mi:“MI:0915”(physical association)	0.400
TSPAN17	MGST3	psi-mi:“MI:0914”(association)	0.350
TSPAN17	HACD3	psi-mi:“MI:0915”(physical association)	0.000
TSPAN17	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (119): TSPAN17 (Affinity Capture-RNA), ADAM10 (Affinity Capture-Western), ATP2A3 (Affinity Capture-MS), PNPLA6 (Affinity Capture-MS), DGKE (Affinity Capture-MS), TBL2 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), DHRS7 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), GHDC (Affinity Capture-MS), AGPAT4 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS)

ESM2 similar proteins: O43657, O46101, O60635, O70352, O70401, O97703, P08962, P19075, P19331, P19397, P24485, P27591, P27701, P28648, P35762, P40237, P41731, P41732, P60033, P60034, P62079, P62080, Q17QJ5, Q26499, Q28709, Q2KIS9, Q32KU6, Q3T0S3, Q3ZCD0, Q4R7W6, Q4V8E0, Q58DM3, Q58DN3, Q5R9S6, Q5RAS5, Q5RC27, Q61451, Q62283, Q62745, Q68VK5

Diamond homologs: A1L157, B5X3I6, O14817, O35566, O60636, O70352, P19075, P24485, P27701, P40241, P48509, P60033, P60034, P61170, P61171, Q0VC33, Q3ZBH3, Q4V8E0, Q568Y5, Q58CY8, Q58DN3, Q5R9S6, Q5RAP3, Q61451, Q80WR1, Q8WMQ3, Q96FV3, Q96SJ8, Q9D1D1, Q9D7W4, Q9DCK3, Q9JJW1, Q9QZA6, F7BWT7, O95858, P62079, P62080, Q17QJ5, Q1JQA4, Q3SYV5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1549 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176647700:TGGG:T	donor_loss	1.0000
5:176647701:GG:G	donor_gain	1.0000
5:176647702:GG:G	donor_gain	1.0000
5:176647702:GGT:G	donor_loss	1.0000
5:176647703:G:GG	donor_gain	1.0000
5:176647704:T:A	donor_loss	1.0000
5:176651897:GTTT:G	donor_gain	1.0000
5:176651901:G:GG	donor_gain	1.0000
5:176652757:C:A	acceptor_gain	1.0000
5:176652908:GAA:G	donor_gain	1.0000
5:176652914:G:GG	donor_gain	1.0000
5:176654891:ACAGT:A	acceptor_gain	1.0000
5:176654892:CAG:C	acceptor_loss	1.0000
5:176654893:A:AG	acceptor_gain	1.0000
5:176654893:A:AT	acceptor_loss	1.0000
5:176654893:AGT:A	acceptor_gain	1.0000
5:176654893:AGTG:A	acceptor_gain	1.0000
5:176654894:G:GT	acceptor_gain	1.0000
5:176654894:GT:G	acceptor_gain	1.0000
5:176654894:GTG:G	acceptor_gain	1.0000
5:176654894:GTGG:G	acceptor_gain	1.0000
5:176654894:GTGGT:G	acceptor_gain	1.0000
5:176656076:AGGAG:A	acceptor_gain	1.0000
5:176656077:GGAGG:G	acceptor_gain	1.0000
5:176656122:ACTGG:A	donor_loss	1.0000
5:176656126:G:GG	donor_gain	1.0000
5:176656127:T:G	donor_loss	1.0000
5:176656132:GGG:G	donor_gain	1.0000
5:176656133:GGG:G	donor_gain	1.0000
5:176656697:CAG:C	acceptor_loss	1.0000

AlphaMissense

2168 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000153661 (5:176648525 C>T), RS1000214522 (5:176653799 T>C), RS1000275022 (5:176651335 A>G), RS1000401913 (5:176646544 C>T), RS1000486767 (5:176659273 C>T), RS1000756279 (5:176659089 C>T), RS1000770271 (5:176656982 C>T), RS1001076636 (5:176657152 T>C), RS1001402098 (5:176654677 G>A), RS1001686584 (5:176647466 G>A,C), RS1001947858 (5:176649899 A>C,G), RS1002176958 (5:176651377 G>A), RS1002207935 (5:176651105 G>A), RS1002303937 (5:176650170 G>A), RS1002592874 (5:176647773 G>A)

Disease associations

OMIM: gene MIM:620446 | 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
GCST009921_4	Carotid intima media thickness (mean)	3.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
bufotalin	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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