TSPAN16

Summary

TSPAN16 (tetraspanin 16, HGNC:30725) is a protein-coding gene on chromosome 19p13.2, encoding Tetraspanin-16 (Q9UKR8).

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. This encoded protein might couple to signal transduction pathways and possibly modulate cellular activation and adhesion in haemopoietic and neural tissue. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26526 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001282509

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30725
Approved symbol	TSPAN16
Name	tetraspanin 16
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TM4-B, TM-8
Ensembl gene	ENSG00000130167
Ensembl biotype	protein_coding
OMIM	617580
Entrez	26526

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

ENST00000316737, ENST00000337994, ENST00000589928, ENST00000590327, ENST00000592955, ENST00000621731

RefSeq mRNA: 3 — MANE Select: NM_001282509 NM_001282509, NM_001282510, NM_012466

CCDS: CCDS12256, CCDS62549, CCDS62550

Canonical transcript exons

ENST00000590327 — 7 exons

Exon	Start	End
ENSE00000894023	11298142	11298339
ENSE00000894024	11298872	11298946
ENSE00000894025	11301201	11301308
ENSE00001256032	11306604	11306756
ENSE00002961116	11296160	11296366
ENSE00003681996	11312139	11312222
ENSE00003690624	11315791	11315967

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 99.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1109 / max 66.7606, expressed in 11 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173906	0.0707	3
173907	0.0375	8
173905	0.0026	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.36	gold quality
left testis	UBERON:0004533	96.56	gold quality
right testis	UBERON:0004534	96.53	gold quality
testis	UBERON:0000473	93.65	gold quality
buccal mucosa cell	CL:0002336	90.96	silver quality
adult organism	UBERON:0007023	83.81	gold quality
pancreatic ductal cell	CL:0002079	83.47	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.64	gold quality
blood	UBERON:0000178	72.48	gold quality
monocyte	CL:0000576	72.13	gold quality
leukocyte	CL:0000738	71.92	gold quality
granulocyte	CL:0000094	70.57	gold quality
tendon of biceps brachii	UBERON:0008188	70.40	gold quality
myocardium	UBERON:0002349	68.53	gold quality
upper arm skin	UBERON:0004263	67.14	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.29	gold quality
left ventricle myocardium	UBERON:0006566	66.03	gold quality
quadriceps femoris	UBERON:0001377	59.84	gold quality
bone marrow	UBERON:0002371	59.71	gold quality
parotid gland	UBERON:0001831	59.66	gold quality
deltoid	UBERON:0001476	59.36	gold quality
vastus lateralis	UBERON:0001379	58.89	gold quality
nasal cavity epithelium	UBERON:0005384	58.46	gold quality
tibialis anterior	UBERON:0001385	58.41	silver quality
medial globus pallidus	UBERON:0002477	57.94	gold quality
epithelial cell of pancreas	CL:0000083	57.50	gold quality
bone marrow cell	CL:0002092	57.11	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	56.94	gold quality
cartilage tissue	UBERON:0002418	56.62	gold quality
decidua	UBERON:0002450	56.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.60
E-ANND-3	yes	3.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

6 targeting TSPAN16, 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-185-3P	99.95	67.01	1743
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-3914	94.91	65.77	643

Literature-anchored findings (GeneRIF, showing 1)

• To probe the structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57 amino acid residues was mutated to cysteine. (PMID:29654220)

Cross-species orthologs

0 orthologs

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), 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-16 — Q9UKR8 (reviewed: Q9UKR8)

Alternative names: Tetraspanin TM4-B, Transmembrane 4 superfamily member 16

All UniProt accessions (2): Q9UKR8, K7EMI8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Broadly expressed in most human tissues and cell lines including neural and bone marrow derived tissues.

Similarity. Belongs to the tetraspanin (TM4SF) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UKR8-1	1	yes
Q9UKR8-2	2
Q9UKR8-3	3
Q9UKR8-4	4

RefSeq proteins (3): NP_001269438, NP_001269439, NP_036598 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00335

UniProt features (17 total): topological domain 5, splice variant 4, transmembrane region 4, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKR8-F1	85.17	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 19 (showing top): WGTTNNNNNAAA_UNKNOWN, chr19p13, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ZNF768_TARGET_GENES, MIR548AR_3P, MIR548F_3P, MIR548BC, MIR548AZ_3P, MIR548A_3P, MIR548E_3P, MIR3919, MIR6887_3P, MIR1909_5P, DESCARTES_MAIN_FETAL_PDE1C_ACSM3_POSITIVE_CELLS, HARALAMBIEVA_PBMC_FLUARIX_AGE_50_74YO_CORR_WITH_28D_MEM_B_CELL_RESPONSE_AT_0DY_NEGATIVE

GO Biological Process (0):

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN16	TPM3	P06753	997
TSPAN16	TRPC4	Q9UBN4	720
TSPAN16	SLC6A4	P31645	693
TSPAN16	TRPC5	Q9UL62	669
TSPAN16	FBLN7	Q53RD9	644
TSPAN16	EPB41	P11171	599
TSPAN16	SPTB	P11277	582
TSPAN16	APH1A	Q96BI3	553
TSPAN16	CFTR	P13569	546
TSPAN16	MCHR1	Q99705	544
TSPAN16	SLC1A3	P43003	506
TSPAN16	ANK1	P16157	497
TSPAN16	ANK3	Q12955	495
TSPAN16	ANK2	Q01484	491
TSPAN16	SLC1A1	P43005	479

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TSPAN16	CADM4	psi-mi:“MI:0915”(physical association)	0.500
TSPAN16	ENDOD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): IGHM (Affinity Capture-MS), CADM4 (Affinity Capture-MS), TMEM179B (Affinity Capture-MS), EIF2AK3 (Affinity Capture-MS), BSCL2 (Affinity Capture-MS), ATP7B (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), TMEM159 (Affinity Capture-MS), GLRB (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), ABCA7 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), UGT8 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8RY99, A0PK11, A2RVU1, A6NGA9, A9UL59, B2RVW2, E9Q9H8, O14894, O95473, P0DP42, P30408, P48230, P49111, P56749, Q0IIL2, Q0P4G7, Q11098, Q2KIG8, Q2YDD6, Q32KQ5, Q3T0Z4, Q3T110, Q3UUA0, Q53R12, Q5R6Z4, Q5R9K1, Q5REK8, Q60771, Q64302, Q6AYR5, Q6CUG3, Q6CXZ7, Q6DDK3, Q6GV27, Q6ICI0, Q8BHH8, Q8CJ58, Q8NCR9, Q8VHW1, Q8WXS4

Diamond homologs: A0A8M2B5N2, A0A8V0ZLT4, A1L157, B3VSC2, B5X3I6, O14817, O35566, O60636, O97703, P11049, P19397, P24485, P27591, P30932, P35762, P48509, P60033, P60034, Q06AA5, Q0VC33, Q11098, Q2KIS9, Q3T0S3, Q3ZCD0, Q4V8E0, Q568Y5, Q58CY8, Q58DM3, Q58DN3, Q5RAP3, Q61451, Q62745, Q6AYR9, Q6GMK6, Q80WR1, Q8NG11, Q8QZY6, Q8WMQ3, Q922J6, Q96FV3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1014 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11298125:T:TA	acceptor_gain	1.0000
19:11298336:GTTT:G	donor_gain	1.0000
19:11298340:G:GG	donor_gain	1.0000
19:11301197:T:TA	acceptor_gain	1.0000
19:11306602:A:AG	acceptor_gain	1.0000
19:11306603:G:GG	acceptor_gain	1.0000
19:11312133:CCTCA:C	acceptor_loss	1.0000
19:11312134:CTCA:C	acceptor_loss	1.0000
19:11312135:TCA:T	acceptor_loss	1.0000
19:11312136:CAG:C	acceptor_loss	1.0000
19:11312137:AG:A	acceptor_gain	1.0000
19:11312137:AGGG:A	acceptor_loss	1.0000
19:11312138:GG:G	acceptor_gain	1.0000
19:11312138:GGGCT:G	acceptor_gain	1.0000
19:11312218:TACAG:T	donor_loss	1.0000
19:11312219:ACAG:A	donor_loss	1.0000
19:11312220:CAGGT:C	donor_loss	1.0000
19:11312221:AGGTA:A	donor_loss	1.0000
19:11312222:GGT:G	donor_loss	1.0000
19:11312224:T:A	donor_loss	1.0000
19:11296572:A:G	donor_gain	0.9900
19:11298140:AGGTG:A	acceptor_loss	0.9900
19:11298141:G:A	acceptor_loss	0.9900
19:11298299:G:GA	donor_gain	0.9900
19:11298327:C:T	donor_gain	0.9900
19:11298337:TTT:T	donor_gain	0.9900
19:11298338:TTGTA:T	donor_loss	0.9900
19:11298339:TGTAA:T	donor_loss	0.9900
19:11298341:T:TC	donor_loss	0.9900
19:11300973:A:G	donor_gain	0.9900

AlphaMissense

1572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11306637:T:C	F162L	0.993
19:11306639:T:A	F162L	0.993
19:11306639:T:G	F162L	0.993
19:11306638:T:G	F162C	0.988
19:11306652:T:C	F167L	0.987
19:11306654:C:A	F167L	0.987
19:11306654:C:G	F167L	0.987
19:11306638:T:C	F162S	0.980
19:11306653:T:G	F167C	0.979
19:11301290:G:C	W144C	0.971
19:11301290:G:T	W144C	0.971
19:11301288:T:A	W144R	0.969
19:11301288:T:C	W144R	0.969
19:11306613:T:A	C154S	0.950
19:11306614:G:C	C154S	0.950
19:11306610:T:A	C153S	0.945
19:11306611:G:C	C153S	0.945
19:11301280:C:T	S141F	0.943
19:11301302:G:A	M148I	0.943
19:11301302:G:C	M148I	0.943
19:11301302:G:T	M148I	0.943
19:11306617:G:A	G155E	0.940
19:11306676:T:G	Y175D	0.939
19:11306688:T:A	C179S	0.938
19:11306689:G:C	C179S	0.938
19:11298268:T:C	C66R	0.936
19:11306691:T:A	C180S	0.936
19:11306692:G:C	C180S	0.936
19:11306715:T:A	C188S	0.935
19:11306716:G:C	C188S	0.935

dbSNP variants (sampled 300 via entrez): RS1000046177 (19:11299151 C>A,G,T), RS1000077410 (19:11299338 A>T), RS1000192517 (19:11324606 C>T), RS1000239102 (19:11320008 C>CG), RS1000323193 (19:11305705 T>C), RS1000387068 (19:11318051 G>C), RS1000486236 (19:11311623 A>C,G), RS1000581120 (19:11304404 G>A), RS1000652466 (19:11305453 C>T), RS1000669160 (19:11316454 T>C,G), RS1000796031 (19:11321224 A>C), RS1000823381 (19:11310375 C>T), RS1000853154 (19:11321411 C>T), RS1000878478 (19:11324403 C>T), RS1000930258 (19:11323385 G>A)

Disease associations

OMIM: gene MIM:617580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001904_5	HDL cholesterol	3.000000e-09
GCST005077_6	Breast cancer	7.000000e-09
GCST006611_133	HDL cholesterol	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs322144	TSPAN16		0.00	0

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	4
CGP 52608	increases reaction, affects binding	1
Arsenic	affects methylation	1
Cadmium	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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