CD9

Summary

CD9 (CD9 molecule, HGNC:1709) is a protein-coding gene on chromosome 12p13.31, encoding CD9 antigen (P21926). Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion.

This gene encodes a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Tetraspanins are cell surface glycoproteins with four transmembrane domains that form multimeric complexes with other cell surface proteins. The encoded protein functions in many cellular processes including differentiation, adhesion, and signal transduction, and expression of this gene plays a critical role in the suppression of cancer cell motility and metastasis.

Source: NCBI Gene 928 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_001769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1709
Approved symbol	CD9
Name	CD9 molecule
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	BA2, P24, TSPAN29, MRP-1
Ensembl gene	ENSG00000010278
Ensembl biotype	protein_coding
OMIM	143030
Entrez	928

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 20 protein_coding, 9 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000009180, ENST00000382515, ENST00000382518, ENST00000382519, ENST00000481267, ENST00000536586, ENST00000538418, ENST00000538834, ENST00000540891, ENST00000543916, ENST00000546073, ENST00000610354, ENST00000642746, ENST00000645368, ENST00000645565, ENST00000646407, ENST00000676638, ENST00000676764, ENST00000676788, ENST00000677318, ENST00000677572, ENST00000677585, ENST00000677718, ENST00000678719, ENST00000679331, ENST00000894339, ENST00000894340, ENST00000894341, ENST00000924981, ENST00000924982, ENST00000924983, ENST00000924984, ENST00000947407

RefSeq mRNA: 14 — MANE Select: NM_001769 NM_001330312, NM_001413241, NM_001413242, NM_001413243, NM_001413244, NM_001413245, NM_001413246, NM_001413247, NM_001413248, NM_001413249, NM_001413250, NM_001413251, NM_001413252, NM_001769

CCDS: CCDS81654, CCDS8540

Canonical transcript exons

ENST00000009180 — 8 exons

Exon	Start	End
ENSE00001832813	6200400	6200565
ENSE00003501746	6236192	6236275
ENSE00003610238	6232632	6232729
ENSE00003635630	6233412	6233486
ENSE00003646744	6235476	6235565
ENSE00003653329	6235229	6235327
ENSE00003668112	6225426	6225534
ENSE00003848695	6237763	6238266

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 223.2810 / max 2919.6321, expressed in 1728 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123626	213.6073	1724
123625	8.8651	1610
123624	0.4838	253
123627	0.2047	71
123623	0.1069	27
123628	0.0133	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pharyngeal mucosa	UBERON:0000355	99.83	gold quality
seminal vesicle	UBERON:0000998	99.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.78	gold quality
colonic mucosa	UBERON:0000317	99.74	gold quality
trigeminal ganglion	UBERON:0001675	99.73	gold quality
calcaneal tendon	UBERON:0003701	99.73	gold quality
esophagus squamous epithelium	UBERON:0006920	99.73	gold quality
urethra	UBERON:0000057	99.72	gold quality
synovial joint	UBERON:0002217	99.72	gold quality
bronchial epithelial cell	CL:0002328	99.70	gold quality
oral cavity	UBERON:0000167	99.69	gold quality
epithelium of esophagus	UBERON:0001976	99.69	gold quality
nasal cavity mucosa	UBERON:0001826	99.68	gold quality
nasal cavity epithelium	UBERON:0005384	99.64	gold quality
palpebral conjunctiva	UBERON:0001812	99.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.61	gold quality
gingiva	UBERON:0001828	99.60	gold quality
penis	UBERON:0000989	99.59	gold quality
epithelium of bronchus	UBERON:0002031	99.59	gold quality
bronchus	UBERON:0002185	99.59	gold quality
esophagus mucosa	UBERON:0002469	99.58	gold quality
trachea	UBERON:0003126	99.58	gold quality
gingival epithelium	UBERON:0001949	99.55	gold quality
upper arm skin	UBERON:0004263	99.55	gold quality
mucosa of transverse colon	UBERON:0004991	99.55	gold quality
mouth mucosa	UBERON:0003729	99.53	gold quality
mucosa of stomach	UBERON:0001199	99.52	gold quality
cartilage tissue	UBERON:0002418	99.52	gold quality
lower lobe of lung	UBERON:0008949	99.52	gold quality
minor salivary gland	UBERON:0001830	99.51	gold quality

Single-cell (SCXA)

Detected in 44 experiment(s), a significant marker in 39.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	12004.01
E-HCAD-11	yes	5163.27
E-MTAB-8410	yes	4889.04
E-CURD-46	yes	4450.07
E-MTAB-8322	yes	3494.48
E-CURD-114	yes	2142.87
E-MTAB-9067	yes	2026.19
E-HCAD-1	yes	1826.33
E-HCAD-6	yes	1495.79
E-MTAB-8221	yes	1286.21
E-HCAD-9	yes	1197.66
E-GEOD-137537	yes	985.93
E-MTAB-11121	yes	823.48
E-HCAD-4	yes	77.46
E-CURD-122	yes	67.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EGR1, FOSB, JUN, PITX2, SP1, STAT3

Literature-anchored findings (GeneRIF, showing 40)

• peripheral blood monocytes treated for 5–8 days with GM-CSF (i.e. mature Mphi) acquired the capacity to assemble CD9 with alpha3-beta1 integrin, tyrosine phosphatase SHP-1 and with CD46. (PMID:11858824)
• CD9 protein expression was inversely associated with lymph node metastasis. (PMID:11920609)
• By site-directed mutagenesis, CD9 was found to be palmitoylated at any of the four internal juxtamembrane regions. (PMID:11959120)
• C-kit is physically associated with transmembrane 4 superfamily proteins CD9, CD63, and CD81, that may negatively modulate c-kit and thus regulate c-kit receptor sensitivity to SLF in hematopoietic progenitors. (PMID:12036870)
• Infertility of CD9-deficient mouse eggs is reversed by human CD9 (PMID:12086470)
• Data show that the expression of the PAINS-13 epitope depends on CD9 association with alpha(6)beta(1) integrin. (PMID:12411441)
• The second extracellular loop sequence (173)LETFTVKSCPDAIKEVFDNK(192) is largely responsible for trasnfected human CD9-mediated CHO cell adhesion to fibronectin and fibronectin pericellular matrix assembly. (PMID:12453879)
• low expression of CD9 may contribute to the highly invasive and metastatic phenotype of small cell lung cancer (PMID:12569360)
• downregulation of CD9 antigen is associated with breast tumor progression (PMID:12579280)
• CD9 expression was rather intensified in gastric cancer tissue in comparison with normal tissues. CD9 expression was more prominent in advanced gastric cancer. (PMID:15047125)
• CD9 does not have a role in progression of human osteosarcoma or predict its prognosis (PMID:15145525)
• CD9 activates the p46 Shc isoform in tumor cells and leads to apoptosis (PMID:15226408)
• cell-surface expression of CD9, a beta1 integrin-associated transmembrane protein that is involved in cell adhesion and cell motility events, was enhanced in the ra-a47 anti-sense oligonucleotide-treated cells. (PMID:15389525)
• The MRP-1/CD9 gene expression was down-regulated in gastric cancer, its expression was probably related to the carcinogenesis and histology types of gastric cancer. (PMID:15476162)
• endothelial CD9 tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (PMID:15591117)
• leukocyte antigen-DR, CD38, and CD9 share a common pathway of tyrosine kinase activation in human monocytes (PMID:15941914)
• tetraspanin intra- and intermolecular interactions are mediated by conserved residues in adjacent, but distinct regions of TM1 and TM2 (PMID:15985154)
• phenotypic conversion and reversion of bladder cancer cells is controlled by a glycosynapse 3 microdomain through GM3-mediated interaction of alpha3beta1 integrin with CD9 (PMID:16103120)
• results have shown that CD-9 is present in prostate tumour epithelial cells and that it is regulated by androgens in LNCaP-FGC cells (PMID:16128989)
• CD9 is essential for the IL-16-mediated chemotaxis and activation, acting as an IL-16 receptor in HMC-1, a mast cell line that lacks CD4 (PMID:16144798)
• A role of CD9 in melanocyte motility was shown. (PMID:16297202)
• results suggest that the restored expression of CD9 in SCLC cells may reduce the metastatic spread of SCLC cells via the inhibition of cell proliferation and motility (PMID:16491954)
• EWI proteins EWI-2 and EWI-F, alpha3beta1 and alpha6beta4 integrins, and protein palmitoylation have contrasting effects on cell surface CD9 organization (PMID:16537545)
• MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway. (PMID:16682943)
• CD9 expression by multiple myeloma cells is upregulated in vivo by close interaction of the cells with endothelial cells and CD9 is involved in transendothelial invasion (PMID:16900214)
• CD9 molecules on endothelial cells participate in the mitogenic effect of platelets; results suggest that the tetraspanin CD9 plays an important role in endothelial regeneration (PMID:16951553)
• role of CD81 and CD9 on the cell-to-cell fusion process mediated by HIV-1, syncytia formation induced by HIV-1 envelope proteins and viral entry in human T lymphoblasts (PMID:17015697)
• Ectopic CD9 expression suppressed neurite-like process outgrowth & promoted apoptotic death of some SCLC cells. Its absence in SLCL may contribute to postadhesive morphologic differentiation, survival, & MMP-2 production via PI3K/Akt pathway. (PMID:17018612)
• results clearly point to an involvement of CD9 in the attachment, uptake or processing of adeno-associated virus-2 by target cells (PMID:17203208)
• Expression of CD9 in transitional cell carcinoma bladder is reported. (PMID:17393117)
• CD9 gene inactivation may play an important role in prostate cancer progression. (PMID:17406028)
• transferrin receptor and CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells (PMID:17407154)
• Data show that HIV-1 envelope glycoprotein (Env) and core protein (Gag) colocalize strongly with CD63 and CD81 and less strongly with CD9, and suggest that HIV-1 promotes virus assembly and cell-cell transfer by targeting these plasma membrane proteins. (PMID:17522207)
• establish for the first time a role for CD9 in the tumorigenic process (PMID:17582603)
• Nine potential tetraspanin CD9 partners, including claudin-1, were identified. (PMID:17644758)
• CD9 plays roles in cell proliferation and attachment in vitro as well as in in vivo engraftment and that it can be considered as a useful marker to predict the in vivo efficacy of human adipose-derived mesenchymal stem cells. (PMID:17668233)
• CD10 and CD9 expression correlates with the invasiveness and metastatic potential of malignant melanoma. (PMID:17845760)
• The absence or down-regulation of CD9 expression and point mutation may play a considerable role in the pathway of the malignant transformation in the BEAS-2B cells induced by mineral powder. (PMID:17997888)
• examined whether CD63-PI4K55 and CD9-PI4K55 complexes were resident in platelet-lipid rafts, or formed distinct microdomains (PMID:18000614)
• Results demonstrate the physical and functional association of CD9 with epidermal growth factor receptor on MKN-28 cells. (PMID:18247373)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd9	ENSMUSG00000030342
rattus_norvegicus	Cd9	ENSRNOG00000019556

Paralogs (32): TSPAN6 (ENSG00000000003), 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), 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

CD9 antigen — P21926 (reviewed: P21926)

Alternative names: 5H9 antigen, Cell growth-inhibiting gene 2 protein, Leukocyte antigen MIC3, Motility-related protein, Tetraspanin-29, p24

All UniProt accessions (8): P21926, A0A087WU13, A0A2R8Y478, A0A7I2V3T0, A0A7I2V3T7, A6NNI4, F5GXT1, G8JLH6

UniProt curated annotations — full annotation on UniProt →

Function. Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion. Present at the cell surface of oocytes and plays a key role in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion. In myoblasts, associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration. In macrophages, associates with CD81 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption. Acts as a receptor for PSG17. Involved in platelet activation and aggregation. Regulates paranodal junction formation. Involved in cell adhesion, cell motility and tumor metastasis.

Subunit / interactions. Forms both disulfide-linked homodimers and higher homooligomers as well as heterooligomers with other members of the tetraspanin family. Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3. Interacts with integrin ITGA6:ITGB1; interaction takes place in oocytes and is involved in sperm-egg fusion. Part of integrin-tetraspanin complexes composed of CD81, beta-1 and beta-2 integrins in the membrane of monocyte/macrophages. Interacts with CD63; identified in a complex with CD63 and ITGB3. Associates with CR2/CD21 and with PTGFRN/CD9P1. Part of a complex composed of CD9, CD81, PTGFRN and IGSF8. Interacts directly with IGSF8. Interacts with PDPN; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Interacts (on T cell side) with CD81 at immunological synapses between antigen-presenting cells and T cells.

Subcellular location. Cell membrane. Membrane. Secreted. Extracellular exosome.

Tissue specificity. Detected in platelets (at protein level). Expressed by a variety of hematopoietic and epithelial cells.

Post-translational modifications. Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro). The protein exists in three forms with molecular masses between 22 and 27 kDa, and is known to carry covalently linked fatty acids. Palmitoylation by ZDHHC2 regulates CD9 expression, association with other tetraspanin family proteins and function in cell adhesion.

Similarity. Belongs to the tetraspanin (TM4SF) family.

RefSeq proteins (14): NP_001317241, NP_001400170, NP_001400171, NP_001400172, NP_001400173, NP_001400174, NP_001400175, NP_001400176, NP_001400177, NP_001400178, NP_001400179, NP_001400180, NP_001400181, NP_001760* (*=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
IPR042055	CD9_LEL	Domain

Pfam: PF00335

UniProt features (41 total): helix 11, lipid moiety-binding region 6, mutagenesis site 6, topological domain 5, transmembrane region 4, glycosylation site 2, disulfide bond 2, turn 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6Z1V	X-RAY DIFFRACTION	1.33
6RLR	X-RAY DIFFRACTION	2
6RLO	X-RAY DIFFRACTION	2.2
6Z20	X-RAY DIFFRACTION	2.68
6K4J	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21926-F1	88.38	0.61

Antibody-complex structures (SAbDab): 3 — 6RLO, 6Z1V, 6Z20

Functional residue map

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

Post-translational modifications (6): 9, 78, 79, 87, 218, 219

Disulfide bonds (2): 152–181, 153–167

Glycosylation sites (2): 52, 53

Mutagenesis-validated functional residues (6):

Position	Phenotype
9	loss of palmitoylation; when associated with a-78; a-79; a-87; a-218 and a-219.
78	loss of palmitoylation; when associated with a-9; a-79; a-87; a-218 and a-219.
79	loss of palmitoylation; when associated with a-9; a-78; a-87; a-218 and a-219.
87	loss of palmitoylation; when associated with a-9; a-78; a-79; a-218 and a-219.
218	loss of palmitoylation; when associated with a-9; a-78; a-79; a-87 and a-219.
219	loss of palmitoylation; when associated with a-9; a-78; a-79; a-87 and a-218.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1300645	Acrosome Reaction and Sperm:Oocyte Membrane Binding
R-HSA-5336415	Uptake and function of diphtheria toxin
R-HSA-109582	Hemostasis
R-HSA-1187000	Fertilization
R-HSA-1474165	Reproduction
R-HSA-1643685	Disease
R-HSA-5339562	Uptake and actions of bacterial toxins
R-HSA-5663205	Infectious disease
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-9824439	Bacterial Infection Pathways

MSigDB gene sets: 544 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SINGLE_FERTILIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LEE_NEURAL_CREST_STEM_CELL_DN, CHIBA_RESPONSE_TO_TSA_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MACLACHLAN_BRCA1_TARGETS_DN, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION

GO Biological Process (17): cell adhesion (GO:0007155), fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), glial cell migration (GO:0008347), oligodendrocyte development (GO:0014003), myoblast fusion involved in skeletal muscle regeneration (GO:0014905), platelet activation (GO:0030168), paranodal junction assembly (GO:0030913), receptor internalization (GO:0031623), sperm-egg recognition (GO:0035036), cellular response to low-density lipoprotein particle stimulus (GO:0071404), negative regulation of platelet aggregation (GO:0090331), regulation of macrophage migration (GO:1905521), single fertilization (GO:0007338), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (2): integrin binding (GO:0005178), protein binding (GO:0005515)

GO Cellular Component (14): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), membrane (GO:0016020), apical plasma membrane (GO:0016324), endocytic vesicle membrane (GO:0030666), clathrin-coated endocytic vesicle membrane (GO:0030669), platelet alpha granule membrane (GO:0031092), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561), extracellular region (GO:0005576), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Fertilization	1
Uptake and actions of bacterial toxins	1
Reproduction	1
Bacterial Infection Pathways	1
Disease	1
Hemostasis	1
Platelet activation, signaling and aggregation	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
single fertilization	2
cellular process involved in reproduction in multicellular organism	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell migration	1
gliogenesis	1
glial cell development	1
oligodendrocyte differentiation	1
myoblast fusion	1
myotube differentiation involved in skeletal muscle regeneration	1
skeletal muscle tissue regeneration	1
cell activation	1
blood coagulation	1
cell-cell junction assembly	1
cellular component assembly involved in morphogenesis	1
myelin assembly	1
receptor-mediated endocytosis	1
cell-cell recognition	1
response to lipoprotein particle	1
cellular response to lipoprotein particle stimulus	1
negative regulation of platelet activation	1
negative regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
regulation of mononuclear cell migration	1
macrophage migration	1
fertilization	1
system development	1
cellular developmental process	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
binding	1
membrane	1
cell periphery	1
cell-substrate junction	1
plasma membrane	1

Protein interactions and networks

STRING

3214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD9	PTGFRN	Q9P2B2	998
CD9	IGSF8	Q969P0	997
CD9	TSG101	Q99816	996
CD9	CD81	P18582	988
CD9	CD63	P08962	988
CD9	HBEGF	Q99075	980
CD9	CD82	P27701	977
CD9	CD44	P16070	968
CD9	ITGB1	P05556	953
CD9	HSPA4	P34932	947
CD9	EPCAM	P16422	941
CD9	ITGA3	P26006	918
CD9	ICAM1	P05362	912
CD9	SDCBP	O00560	896
CD9	FKBP11	Q9NYL4	895

IntAct

85 interactions, top by confidence:

A	B	Type	Score
CD9	PTGFRN	psi-mi:“MI:0915”(physical association)	0.860
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	IGSF8	psi-mi:“MI:0914”(association)	0.760
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
ADAM10	CD9	psi-mi:“MI:0914”(association)	0.750
CD9	ADAM10	psi-mi:“MI:0915”(physical association)	0.750
CD9	ADAM10	psi-mi:“MI:0403”(colocalization)	0.750
TSPAN14	ADAM10	psi-mi:“MI:0914”(association)	0.740
CD81	ADAM10	psi-mi:“MI:0914”(association)	0.740
CD9	ITGB1	psi-mi:“MI:0914”(association)	0.690
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
CD9	ODF4	psi-mi:“MI:0915”(physical association)	0.560
CD151	ADAM10	psi-mi:“MI:0914”(association)	0.530
PTGFRN	ADAM10	psi-mi:“MI:0914”(association)	0.530

BioGRID (131): PTGFRN (Affinity Capture-Western), CD9 (Affinity Capture-Western), CD9 (Affinity Capture-MS), CD9 (Affinity Capture-MS), CD9 (Affinity Capture-Western), CD9 (Affinity Capture-MS), CD9 (Affinity Capture-Western), CD9 (Affinity Capture-MS), CD9 (Affinity Capture-MS), FLYWCH2 (Affinity Capture-MS), IGSF8 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), PTGFRN (Affinity Capture-MS), CD9 (Affinity Capture-MS), ODF4 (Two-hybrid)

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: A1L157, B0BM39, B5X3I6, O14817, O35566, O43657, O60636, O70401, O75954, P08962, P19397, P21926, P24485, P27701, P30409, P30932, P40239, P40240, P40241, P41731, P41732, P48509, P61170, P61171, Q06AA5, Q0VC33, Q28709, Q2KIS9, Q32KU6, Q3ZBH3, Q568Y5, Q58CY8, Q58DM3, Q5RAP3, Q5RAS5, Q61451, Q62283, Q6DCQ3, Q7YQK9, Q7YQL0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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
Extracellular matrix organization	6	8.4×	9e-03
Axon guidance	8	8.0×	1e-03
Nervous system development	8	7.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell migration	8	7.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1578 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6225424:A:AG	acceptor_gain	1.0000
12:6225425:G:GG	acceptor_gain	1.0000
12:6225425:GCTT:G	acceptor_gain	1.0000
12:6225530:CACAG:C	donor_loss	1.0000
12:6225531:ACAGG:A	donor_loss	1.0000
12:6225532:CAG:C	donor_loss	1.0000
12:6225533:AGGTG:A	donor_loss	1.0000
12:6225534:GG:G	donor_loss	1.0000
12:6225535:G:A	donor_loss	1.0000
12:6225536:T:A	donor_loss	1.0000
12:6232628:GCA:G	acceptor_loss	1.0000
12:6232629:CAG:C	acceptor_loss	1.0000
12:6232630:A:AG	acceptor_gain	1.0000
12:6232630:A:AT	acceptor_loss	1.0000
12:6232630:AG:A	acceptor_gain	1.0000
12:6232631:G:GA	acceptor_gain	1.0000
12:6232631:G:T	acceptor_loss	1.0000
12:6232631:GG:G	acceptor_gain	1.0000
12:6232631:GGA:G	acceptor_gain	1.0000
12:6232631:GGAGT:G	acceptor_gain	1.0000
12:6232725:GACTG:G	donor_gain	1.0000
12:6232726:ACTGG:A	donor_loss	1.0000
12:6232730:G:GA	donor_loss	1.0000
12:6232730:G:GG	donor_gain	1.0000
12:6232731:TGAG:T	donor_loss	1.0000
12:6232732:GAGTA:G	donor_loss	1.0000
12:6233408:CCAG:C	acceptor_loss	1.0000
12:6233409:CAGT:C	acceptor_loss	1.0000
12:6233410:A:AG	acceptor_gain	1.0000
12:6233410:AGT:A	acceptor_loss	1.0000

AlphaMissense

1519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6225432:G:A	G25R	1.000
12:6225432:G:C	G25R	1.000
12:6225432:G:T	G25W	1.000
12:6225433:G:A	G25E	1.000
12:6232655:G:C	G67R	1.000
12:6232656:G:A	G67D	1.000
12:6232676:G:C	G74R	1.000
12:6200553:C:A	N18K	0.999
12:6200553:C:G	N18K	0.999
12:6225433:G:T	G25V	0.999
12:6225453:G:A	G32R	0.999
12:6225453:G:C	G32R	0.999
12:6225454:G:A	G32E	0.999
12:6225457:T:C	L33P	0.999
12:6225463:T:C	L35P	0.999
12:6232644:T:C	L63P	0.999
12:6232655:G:T	G67C	0.999
12:6232677:G:A	G74D	0.999
12:6232685:G:C	G77R	0.999
12:6232686:G:A	G77D	0.999
12:6232694:G:A	G80R	0.999
12:6232694:G:C	G80R	0.999
12:6232694:G:T	G80W	0.999
12:6232695:G:A	G80E	0.999
12:6233412:T:C	F92L	0.999
12:6233414:C:A	F92L	0.999
12:6233414:C:G	F92L	0.999
12:6233425:T:C	L96P	0.999
12:6233434:T:A	I99K	0.999
12:6233455:C:A	A106E	0.999

dbSNP variants (sampled 300 via entrez): RS1000194472 (12:6229866 C>A), RS1000202979 (12:6200937 A>T), RS1000208242 (12:6226876 C>T), RS1000231455 (12:6237024 G>C), RS1000285382 (12:6230828 A>C), RS1000353660 (12:6230961 C>T), RS1000498347 (12:6201920 C>A,T), RS1000508553 (12:6238374 G>A), RS1000559734 (12:6220925 G>A), RS1000667528 (12:6232152 G>A,T), RS1000684804 (12:6225653 C>T), RS1000691264 (12:6232548 C>A,G), RS1000859560 (12:6237129 G>A), RS1000885174 (12:6232787 G>A,C), RS1000922583 (12:6222092 G>A)

Disease associations

OMIM: gene MIM:143030 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001335_20	Mean platelet volume	2.000000e-21
GCST001337_34	Platelet count	4.000000e-11
GCST002074_7	Paclitaxel-induced neuropathy	4.000000e-06
GCST002454_10	Colorectal cancer	6.000000e-10
GCST003383_12	Platelet count	2.000000e-07
GCST004599_182	Mean platelet volume	2.000000e-25
GCST007856_2	Colorectal cancer or advanced adenoma	1.000000e-08
GCST007856_26	Colorectal cancer or advanced adenoma	3.000000e-10
GCST90002395_115	Mean platelet volume	1.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	9
Benzo(a)pyrene	affects methylation, increases expression	7
Tretinoin	decreases expression, increases expression	5
trichostatin A	affects cotreatment, increases expression	4
sodium arsenite	increases expression, decreases expression, increases abundance	4
Tetrachlorodibenzodioxin	affects expression, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
Vorinostat	affects cotreatment, affects expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
bisphenol A	increases expression, affects cotreatment, decreases expression	2
cobaltous chloride	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, decreases expression	2
Arsenic	increases abundance, affects methylation, decreases expression	2
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance, increases expression	2
Doxorubicin	increases expression	2
Lead	affects expression, decreases expression	2
Rotenone	decreases expression, increases expression	2
Smoke	increases expression, decreases expression	2
Tetradecanoylphorbol Acetate	increases expression, affects cotreatment, affects expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Zinc	affects cotreatment, affects expression, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
tert-Butylhydroperoxide	decreases expression, affects expression	2
Vitamin K 3	affects expression	2
bisphenol F	decreases expression, affects cotreatment	1

Cellosaurus cell lines

8 cell lines: 8 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1JB	OS3-R5-GFP-CD9	Cancer cell line	Sex unspecified
CVCL_B1ES	Abcam A-549 CD9 KO	Cancer cell line	Male
CVCL_B1MU	Abcam HeLa CD9 KO	Cancer cell line	Female
CVCL_D7M9	Ubigene A-549 CD9 KO	Cancer cell line	Male
CVCL_E1EB	Ubigene U-87 MG CD9 KO	Cancer cell line	Male
CVCL_E3FA	OS3-R5-pZCD9	Cancer cell line	Sex unspecified
CVCL_SI00	HAP1 CD9 (-) 1	Cancer cell line	Male
CVCL_XM62	HAP1 CD9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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