CD63

Summary

CD63 (CD63 molecule, HGNC:1692) is a protein-coding gene on chromosome 12q13.2, encoding CD63 antigen (P08962). Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades.

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 encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak syndrome. Also this gene has been associated with tumor progression. Alternative splicing results in multiple transcript variants encoding different protein isoforms.

Source: NCBI Gene 967 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 42 total
• GTEx eGene: eQTL in 13 tissues, sQTL in 1 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.80 (unconstrained)
• MANE Select transcript: NM_001780
• Interaction hub: 3,660 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1692
Approved symbol	CD63
Name	CD63 molecule
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	ME491, TSPAN30, HOP-26, Pltgp40, AD1
Ensembl gene	ENSG00000135404
Ensembl biotype	protein_coding
OMIM	155740
Entrez	967

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 46 protein_coding, 7 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000257857

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 6, TSL 3: 3, TSL 5: 4

ENST00000257857, ENST00000420846, ENST00000546457, ENST00000546939, ENST00000548117, ENST00000548160, ENST00000548898, ENST00000549117, ENST00000550050, ENST00000550776, ENST00000551173, ENST00000552067, ENST00000552164, ENST00000552692, ENST00000552754, ENST00000555199, ENST00000866659, ENST00000866660, ENST00000866661, ENST00000866662, ENST00000866663, ENST00000866664, ENST00000866665, ENST00000866666, ENST00000866667, ENST00000866668, ENST00000866669, ENST00000866670, ENST00000866671, ENST00000866672, ENST00000866673, ENST00000866674, ENST00000866675, ENST00000922866, ENST00000922867, ENST00000922868, ENST00000922869, ENST00000922870, ENST00000922871, ENST00000922872, ENST00000922873, ENST00000922874, ENST00000922875, ENST00000922876, ENST00000922877, ENST00000944923, ENST00000999897, ENST00000999898, ENST00001018070, ENST00001087561, ENST00001087568, ENST00001087575, ENST00001091733, ENST00001091734, ENST00001136091

RefSeq mRNA: 16 — MANE Select: NM_001780 NM_001257389, NM_001257390, NM_001257391, NM_001257392, NM_001257400, NM_001257401, NM_001267698, NM_001413281, NM_001413282, NM_001413283, NM_001413284, NM_001413285, NM_001413286, NM_001413287, NM_001413288, NM_001780

CCDS: CCDS58242, CCDS58243, CCDS8890

Canonical transcript exons

ENST00000257857 — 8 exons

Exon	Start	End
ENSE00000920077	55728276	55728352
ENSE00001517772	55728953	55729009
ENSE00002325261	55725323	55725626
ENSE00003477196	55726121	55726261
ENSE00003489755	55725813	55725896
ENSE00003567727	55727151	55727339
ENSE00003590609	55726700	55726795
ENSE00003691001	55726890	55726964

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 409.9608 / max 2987.6829, expressed in 1828 samples.

Highest expression (Bgee): stromal cell of endometrium, tendon of biceps brachii, adult organism, type B pancreatic cell, islet of Langerhans.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD63 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.2e-62	-0.28	12:55676990:G:A
Testis	eqtl	1.0e-05	-0.10	12:55727670:G:GC
Cells EBV-transformed lymphocytes	eqtl	5.6e-05	+0.51	12:55717883:G:A
Heart Atrial Appendage	eqtl	9.3e-04	-0.55	12:56461151:C:A
Skin Sun Exposed Lower leg	eqtl	7.8e-03	+0.05	12:55974294:G:A
Esophagus Mucosa	eqtl	1.1e-02	-0.08	12:55717540:A:C
Brain Cerebellum	eqtl	1.2e-02	+0.13	12:56524782:T:C
Nerve Tibial	eqtl	2.3e-02	+0.21	12:56594207:T:C
Cells EBV-transformed lymphocytes	sqtl	2.8e-02	-2.96	12:55565421:G:A
Colon Sigmoid	eqtl	2.9e-02	+0.40	12:55590912:C:T
Stomach	eqtl	3.4e-02	-0.25	12:55727791:TAGAC:T
Lung	eqtl	3.4e-02	-0.27	12:55726739:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.8e-02	+0.20	12:56072895:T:G
Adipose Subcutaneous	eqtl	3.9e-02	-0.07	12:56459447:C:A

FANTOM5 promoters

showing 10 of 13 alternative TSS:

Promoter ID	TPM avg	Samples expressed
131431	365.3902	1828
131430	29.8247	1770
131424	7.0541	1622
131427	2.8257	1088
131432	1.8826	1123
131429	0.8830	485
131428	0.5820	296
131426	0.3501	178
131415	0.3042	77
131422	0.2717	98

Top tissues by expression

showing 100 of 305 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.92	gold quality
tendon of biceps brachii	UBERON:0008188	99.85	gold quality
adult organism	UBERON:0007023	99.79	gold quality
type B pancreatic cell	CL:0000169	99.78	gold quality
islet of Langerhans	UBERON:0000006	99.78	gold quality
lower lobe of lung	UBERON:0008949	99.77	gold quality
left adrenal gland	UBERON:0001234	99.74	gold quality
olfactory bulb	UBERON:0002264	99.74	gold quality
upper lobe of lung	UBERON:0008948	99.74	gold quality
thoracic aorta	UBERON:0001515	99.73	gold quality
descending thoracic aorta	UBERON:0002345	99.73	gold quality
decidua	UBERON:0002450	99.73	gold quality
upper lobe of left lung	UBERON:0008952	99.73	gold quality
smooth muscle tissue	UBERON:0001135	99.72	gold quality
ascending aorta	UBERON:0001496	99.72	gold quality
left adrenal gland cortex	UBERON:0035825	99.72	gold quality
right adrenal gland	UBERON:0001233	99.71	gold quality
adrenal cortex	UBERON:0001235	99.71	gold quality
cardiac atrium	UBERON:0002081	99.71	gold quality
corpus epididymis	UBERON:0004359	99.71	gold quality
right atrium auricular region	UBERON:0006631	99.71	gold quality
gall bladder	UBERON:0002110	99.70	gold quality
adrenal gland	UBERON:0002369	99.70	gold quality
myometrium	UBERON:0001296	99.69	gold quality
coronary artery	UBERON:0001621	99.69	gold quality
left coronary artery	UBERON:0001626	99.69	gold quality
synovial joint	UBERON:0002217	99.69	gold quality
nasal cavity epithelium	UBERON:0005384	99.69	gold quality
right adrenal gland cortex	UBERON:0035827	99.69	gold quality
endocervix	UBERON:0000458	99.68	gold quality
right lobe of thyroid gland	UBERON:0001119	99.68	gold quality
left lobe of thyroid gland	UBERON:0001120	99.68	gold quality
right coronary artery	UBERON:0001625	99.68	gold quality
placenta	UBERON:0001987	99.68	gold quality
right lung	UBERON:0002167	99.68	gold quality
peritoneum	UBERON:0002358	99.68	gold quality
vena cava	UBERON:0004087	99.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.68	gold quality
omental fat pad	UBERON:0010414	99.68	gold quality
aorta	UBERON:0000947	99.67	gold quality
metanephros cortex	UBERON:0010533	99.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.67	gold quality
urethra	UBERON:0000057	99.66	gold quality
trachea	UBERON:0003126	99.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.66	gold quality
body of uterus	UBERON:0009853	99.66	gold quality
body of stomach	UBERON:0001161	99.65	gold quality
mucosa of stomach	UBERON:0001199	99.65	gold quality
left uterine tube	UBERON:0001303	99.65	gold quality
thyroid gland	UBERON:0002046	99.65	gold quality
adenohypophysis	UBERON:0002196	99.65	gold quality
mucosa of transverse colon	UBERON:0004991	99.65	gold quality
layer of synovial tissue	UBERON:0007616	99.65	gold quality
sigmoid colon	UBERON:0001159	99.64	gold quality
superficial temporal artery	UBERON:0001614	99.64	gold quality
artery	UBERON:0001637	99.64	gold quality
lung	UBERON:0002048	99.64	gold quality
popliteal artery	UBERON:0002250	99.64	gold quality
saphenous vein	UBERON:0007318	99.64	gold quality
tibial artery	UBERON:0007610	99.64	gold quality
lower esophagus	UBERON:0013473	99.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.64	gold quality
large intestine	UBERON:0000059	99.63	gold quality
colonic epithelium	UBERON:0000397	99.63	gold quality
rectum	UBERON:0001052	99.63	gold quality
colon	UBERON:0001155	99.63	gold quality
transverse colon	UBERON:0001157	99.63	gold quality
right ovary	UBERON:0002118	99.62	gold quality
trabecular bone tissue	UBERON:0002483	99.62	gold quality
caput epididymis	UBERON:0004358	99.62	gold quality
pituitary gland	UBERON:0000007	99.61	gold quality
stomach	UBERON:0000945	99.61	gold quality
fundus of stomach	UBERON:0001160	99.61	gold quality
pylorus	UBERON:0001166	99.61	gold quality
skin of hip	UBERON:0001554	99.61	gold quality
nasal cavity mucosa	UBERON:0001826	99.61	gold quality
minor salivary gland	UBERON:0001830	99.61	gold quality
pericardium	UBERON:0002407	99.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.61	gold quality
bronchial epithelial cell	CL:0002328	99.60	gold quality
urinary bladder	UBERON:0001255	99.60	gold quality
pancreas	UBERON:0001264	99.60	gold quality
dorsal root ganglion	UBERON:0000044	99.59	gold quality
intestine	UBERON:0000160	99.59	gold quality
heart	UBERON:0000948	99.59	gold quality
cardia of stomach	UBERON:0001162	99.59	gold quality
epithelium of bronchus	UBERON:0002031	99.59	gold quality
bronchus	UBERON:0002185	99.59	gold quality
cartilage tissue	UBERON:0002418	99.59	gold quality
seminal vesicle	UBERON:0000998	99.58	gold quality
nerve	UBERON:0001021	99.58	gold quality
body of pancreas	UBERON:0001150	99.58	gold quality
tibial nerve	UBERON:0001323	99.58	gold quality
trigeminal ganglion	UBERON:0001675	99.58	gold quality
pigmented layer of retina	UBERON:0001782	99.58	gold quality
left ovary	UBERON:0002119	99.58	gold quality
colonic mucosa	UBERON:0000317	99.57	gold quality
right uterine tube	UBERON:0001302	99.57	gold quality
cardiac ventricle	UBERON:0002082	99.56	gold quality

Single-cell (SCXA)

Detected in 47 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	4163.56
E-GEOD-84465	yes	3824.37
E-MTAB-8142	yes	2911.04
E-HCAD-1	yes	2568.79
E-GEOD-139324	yes	2403.00
E-MTAB-10042	yes	1695.24
E-MTAB-10432	yes	1557.93
E-CURD-88	yes	1508.06
E-HCAD-5	yes	1331.97
E-HCAD-8	yes	994.98
E-CURD-77	yes	436.86
E-HCAD-4	yes	213.11
E-MTAB-8410	yes	71.46
E-CURD-122	yes	69.33
E-MTAB-10553	yes	44.20

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Epididymis	tissue	1407.9	medium
Urinary bladder	tissue	778.9	medium
Pancreas	tissue	761.0	low
Adipose tissue	tissue	731.1	not detected
Bone marrow	tissue	705.2	medium
Smooth muscle	tissue	695.2	not detected
Rectum	tissue	690.9	medium
Heart muscle	tissue	684.9	low
Stomach 1	tissue	632.2	medium
Colon	tissue	631.5	low
Lung	tissue	599.8	medium
Cervix	tissue	577.0	medium
Gallbladder	tissue	569.2	medium
Placenta	tissue	552.2	medium
Tongue	tissue	548.4
Liver	tissue	526.9	low
Seminal vesicle	tissue	514.9	medium
Vagina	tissue	501.9	not detected
Breast	tissue	495.7	not detected
Salivary gland	tissue	492.4	not detected
Parathyroid gland	tissue	492.4	low
Adrenal gland	tissue	483.6	low
Ovary	tissue	476.6	not detected
Skeletal muscle	tissue	468.4	not detected
Kidney	tissue	462.2	medium
Thyroid gland	tissue	453.6	medium
Pituitary gland	tissue	449.1
Endometrium 1	tissue	437.7	not detected
Appendix	tissue	432.1	low
Prostate	tissue	408.9	medium
Fallopian tube	tissue	401.3	not detected
Choroid plexus	tissue	381.2
Duodenum	tissue	371.4	low
Small intestine	tissue	362.8	low
Spleen	tissue	333.0	medium
Lymph node	tissue	304.5	low
Esophagus	tissue	290.9	not detected
Tonsil	tissue	266.7	low
Retina	tissue	249.3
Locus coeruleus	tissue	208.8
Skin 1	tissue	193.2	low
Testis	tissue	186.1	medium
Spinal cord	tissue	184.3
Thymus	tissue	180.3
Superior colliculi	tissue	165.5
Substantia nigra	tissue	160.0
Hippocampus	tissue	160.0	not detected
Corpus callosum	tissue	159.7
Medulla oblongata	tissue	156.5
Pons	tissue	142.5
Midbrain	tissue	141.3
Nucleus accumbens	tissue	140.2
Thalamus	tissue	130.6
Periaqueductal gray	tissue	124.9
Hypothalamus	tissue	119.2
Postcentral gyrus	tissue	106.1
Caudate putamen	tissue	104.5
Frontal cortex	tissue	97.8
Septum	tissue	91.6
Putamen	tissue	83.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (1051.1), Anterior thalamic nucleus, ventral (336.2), Supraoptic nucleus (286.8), Nucleus raphe pallidus (286.7), Area postrema (278.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, MYC

miRNA regulators (miRDB)

Targeting CD63 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

12 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
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-4766-5P	99.75	69.23	2662
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-1468-5P	94.18	69.04	176

Functional genomics

gnomAD constraint: pLI 0.0056, LOEUF 0.8, missense Z 1.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000257857 — one region, missense o/e 0.84.

Literature-anchored findings (GeneRIF, showing 40)

• Results show that AP-3 is absolutely required for the delivery of CD63 to lysosomes via the trans-Golgi network. (PMID:11907283)
• 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)
• downregulation of CD63 antigen is associated with breast tumor progression (PMID:12579280)
• possible role in HIV-1 infections specific for macrophages (PMID:12610138)
• Post-translational modification of CD63 may be involved in the functional and morphological changes of MHC class II compartments that occur during dendritic cell maturation (PMID:12755696)
• relationships between the expression levels of CD61, CD63, and PAC-1 on the platelet surface and the incidences of acute rejection and tubular necrosis as well as the recovery of graft function after renal transplantation (PMID:12826159)
• Upon platelet interaction with fibrinogen, cholesterol accumulated at the tips of filopodia and at the leading edge of spreading cells; cholesterol-rich raft aggregation was accompanied by concentration of c-Src and CD63 in these cell domains (PMID:12871315)
• The study on CD63 included its chemistry eg. if it had and O-linked carbohydrate that was digested with O-glycanase. (PMID:12974720)
• CD63 serves as an adaptor protein that links its interaction partners to the endocytic machinery of the cell. (PMID:14660791)
• results suggest that CD9, CD63, CD81, and CD82 could play a role in modulating the interactions between immature DCs and their environment, slowing their migratory ability. However, only CD63 would intervene in the internalization of complex antigens (PMID:15130945)
• Constitutive expression of CD63 may indicate that this factor does not play a direct role in thyroid carcinogenesis (PMID:15375577)
• CD63 represents an activation-induced reinforcing element, whose triggering promotes sustained and efficient T cell activation and expansion. (PMID:15528334)
• The linkage of CD63 with PI 4-kinase may result in the recruitment of this signaling enzyme to specific membrane locations in the platelet where it influences phosphoinositide-dependent signaling and platelet spreading. (PMID:15711748)
• This study identifies a trafficking pathway from CD63-positive multivesicular bodies to the bacterial inclusion, a novel interaction that provides essential lipids necessary for maintenance of a productive intracellular infection. (PMID:16410552)
• CD63 is recruited to already-budded Weibel-Palade bodies by an AP-3-dependent route (PMID:16683915)
• CD63-syntenin-1 complex is abundant on the plasma membrane (PMID:16908530)
• CD63 is a cell surface binding partner for TIMP-1, regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex. (PMID:16917503)
• Chronic urticaria serum-induced CD63 expression assay performed on atopic whole blood by means of tricolor flow cytometry could be the most useful tool for identification of a subset of patients with autoimmune chronic urticaria. (PMID:16918509)
• In conclusion, using well-defined experimental conditions, the measurement of CD203c up-regulation on basophils in response to specific allergens is as reliable as CD63-BAT for the in vitro diagnosis of patients with IgE-mediated allergy. (PMID:17275019)
• positive correlation between CD63 and erythrocyte sedimentation rate in rheumatoid arthritis (PMID:17279322)
• Results suggest that CD63 can be a biomarker for predicting the prognosis in early stages of lung adenocarcinoma. (PMID:17350713)
• These results suggest that chronic obstructive pulmonary disease patients have different patterns of CD63 expression and polymorphonuclear neutrophils mediator release than healthy individuals. (PMID:17390088)
• 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)
• There is low expression of the proteins and mRNA of ME491/CD63 and integrin alpha5 in ovarian cancer. The lower the pathological differentiation is, the more significant the loss of expression is and the more likely metastasis is. (PMID:17624082)
• PrP(c) at the cell surface of cultured human erythroblasts is rapidly internalized through the endosomal pathway, where it colocalizes with the tetraspanin CD63. (PMID:17827389)
• Data show that an N-terminal deletion mutant of CD63 blocks entry of CXCR4-using, T-cell tropic human immunodeficiency virus type 1 (X4 HIV-1) by suppressing CXCR4 surface expression. (PMID:18182005)
• CD63 plays a role in the regulation of ROMK channels through its association with RPTPalpha, which in turn interacts with and activates Src family PTK, thus reducing ROMK activity. (PMID:18211905)
• Together, our results indicate that at least in tissue culture, CD63 expression is not required for either the production or the infectivity of HIV-1. (PMID:18321974)
• These studies confirm CD63 as a constituent in multivesicular body-to-chlamydial inclusion transport but it is not required for this association. (PMID:18426873)
• Induction of hypercortisolism in healthy volunteers was associated with a trend toward higher expression of glycoprotein 53 on the platelet surface. (PMID:18600034)
• CD63 is involved in granule targeting of neutrophil elastase (PMID:18669870)
• Antigen-induced p38 MAPK phosphorylation in human basophils essentially contributes to CD63 upregulation (PMID:18727065)
• the activation-induced degranulation of Fas ligand has distinct requirements and involves different mechanisms than those of the granule markers CD63 and CD107a/Lamp-1 (PMID:19079288)
• Exotest for CD63+ plasma exosomes had limited sensitivity but the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity. Caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in patients group (PMID:19381331)
• CD9, CD81 and CD63 are negative regulators of HIV-1-induced cell-cell fusion. (PMID:19458002)
• Serum sCD163 is a homogenous protein covering more than 94% of the CD163 ectodomain including the haptoglobin-hemoglobin -binding region. (PMID:19581020)
• Surface expression of the novel CD63 variant is a distinguishing feature of mast cells, which are are stable, multiple-use cells capable of surviving and delivering several consecutive hits (PMID:20337613)
• CD63 expression results from only the anaphylactic degranulation form of histamine release. (PMID:20633031)
• this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells (PMID:20693981)
• ameloblastin is expressed in osteoblasts and functions as a promoting factor for osteogenic differentiation via a novel pathway through the interaction between CD63 and integrin beta1 (PMID:21149578)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd63	ENSDARG00000025147
mus_musculus	Cd63	ENSMUSG00000025351
rattus_norvegicus	Cd63	ENSRNOG00000007650
drosophila_melanogaster	Tsp47F	FBGN0033629
caenorhabditis_elegans	tsp-7	WBGENE00006633

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), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99529) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
polydipsia	1
polyuria	1
abnormal fluid regulation	1
decreased urine osmolality	1
abnormal urine homeostasis	1
abnormal kidney collecting duct principal cell morphology	1
increased feces water content	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Chlorocebus aethiops	P61170	100.0%	Diamond
Macaca mulatta	P61171	100.0%	Diamond
Pongo abelii	Q5RE11	100.0%	Diamond
Pan troglodytes	Q7YQL0	100.0%	Diamond
Bos taurus	Q58DN3	99.3%	Diamond
Pongo pygmaeus	Q7YQK9	98.4%	Diamond
Sus scrofa	Q06AA5	97.1%	Diamond
Schistosoma mansoni	P19331	93.1%	Diamond
Schistosoma haematobium	Q26499	93.1%	Diamond
Felis catus	Q76B49	89.9%	Diamond
Oryctolagus cuniculus	Q28709	87.8%	Diamond
Schistosoma japonicum	P27591	83.9%	Diamond
Xenopus laevis	Q6GQF5	83.7%	Diamond
Salmo salar	B5X3I6	78.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GDF11	protein-coding	10220
CD63-AS1	ncRNA	105369779
TMT1B	protein-coding	196410
BLOC1S1	protein-coding	2647
ITGA7	protein-coding	3679
RDH5	protein-coding	5959
SARNP	protein-coding	84324
BLOC1S1-RDH5	ncRNA	100528022
ORMDL2	protein-coding	29095
MMP19	protein-coding	4327
DNAJC14	protein-coding	85406

Protein

Protein identifiers

CD63 antigen — P08962 (reviewed: P08962)

Alternative names: Granulophysin, Lysosomal-associated membrane protein 3, Lysosome integral membrane protein 1, Melanoma-associated antigen ME491, OMA81H, Ocular melanoma-associated antigen, Tetraspanin-30

All UniProt accessions (6): P08962, F8VNT9, F8VV56, F8VWK8, F8VX62, F8W022

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.

Subunit / interactions. Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1. Interacts with CD9. Identified in a complex with CD9 and ITGB3. Interacts with PMEL. Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes. Interacts with SYT7.

Subcellular location. Cell membrane. Lysosome membrane. Late endosome membrane. Endosome. Multivesicular body. Melanosome. Secreted. Extracellular exosome. Cell surface.

Tissue specificity. Detected in platelets (at protein level). Dysplastic nevi, radial growth phase primary melanomas, hematopoietic cells, tissue macrophages.

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).

Miscellaneous. Lack of expression of CD63 in platelets has been observed in a patient with Hermansky-Pudlak syndrome (HPS). Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. This antigen is associated with early stages of melanoma tumor progression.

Similarity. Belongs to the tetraspanin (TM4SF) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P08962-1	1	yes
P08962-2	2
P08962-3	3

RefSeq proteins (16): NP_001244318, NP_001244319, NP_001244320, NP_001244321, NP_001244329, NP_001244330, NP_001254627, NP_001400210, NP_001400211, NP_001400212, NP_001400213, NP_001400214, NP_001400215, NP_001400216, NP_001400217, NP_001771* (*=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
IPR042028	CD63_LEL	Domain

Pfam: PF00335

UniProt features (18 total): topological domain 5, transmembrane region 4, glycosylation site 3, splice variant 2, initiator methionine 1, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
9HUR	Crystal structure of Tetraspanin CD63mutant Large Extracellular Loop (LEL) in complex …	X-RAY DIFFRACTION	1.65
9HQ5	Crystal structure of Tetraspanin CD63mutant Large Extracellular Loop (LEL) in complex …	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08962-F1	90.82	0.80

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 9HQ5, 9HUR

Human Protein Atlas

Protein class: CD markers, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF supported

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 (3)

Type	Positions
N-linked (glcnac…) asparagine	130, 150, 172

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-114608	Platelet degranulation	curated
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	—

MSigDB gene sets: 313 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOCC_CELL_SURFACE, MODULE_128

GO Biological Process (16): positive regulation of receptor internalization (GO:0002092), cell-matrix adhesion (GO:0007160), negative regulation of epithelial cell migration (GO:0010633), protein transport (GO:0015031), cell migration (GO:0016477), epithelial cell differentiation (GO:0030855), endosome to melanosome transport (GO:0035646), positive regulation of cell adhesion (GO:0045785), pigment granule maturation (GO:0048757), regulation of vascular endothelial growth factor signaling pathway (GO:1900746), regulation of potassium ion transmembrane transport (GO:1901379), positive regulation of integrin-mediated signaling pathway (GO:2001046), cell differentiation (GO:0030154), pigmentation (GO:0043473), positive regulation of endocytosis (GO:0045807), pigment cell differentiation (GO:0050931)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (19): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), platelet dense granule membrane (GO:0031088), late endosome membrane (GO:0031902), endosome lumen (GO:0031904), multivesicular body membrane (GO:0032585), protein-containing complex (GO:0032991), azurophil granule membrane (GO:0035577), melanosome (GO:0042470), extracellular exosome (GO:0070062), multivesicular body, internal vesicle (GO:0097487), extracellular region (GO:0005576), lysosome (GO:0005764), late endosome (GO:0005770), multivesicular body (GO:0005771), membrane (GO:0016020), vesicle (GO:0031982)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Innate Immune System	1
Immune System	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
cellular anatomical structure	3
endosome	3
cell differentiation	2
binding	2
secretory granule membrane	2
late endosome	2
multivesicular body	2
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
cell-substrate adhesion	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
negative regulation of multicellular organismal process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell motility	1
epithelium development	1
endosome to pigment granule transport	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
developmental maturation	1
cellular pigment accumulation	1
pigment cell differentiation	1
regulation of signal transduction	1
vascular endothelial growth factor signaling pathway	1
regulation of cellular response to vascular endothelial growth factor stimulus	1
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
integrin-mediated signaling pathway	1
positive regulation of signal transduction	1
regulation of integrin-mediated signaling pathway	1
cellular developmental process	1
biological_process	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
developmental pigmentation	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
platelet dense granule	1
endosome membrane	1
intracellular organelle lumen	1
late endosome membrane	1
cellular_component	1
lysosomal membrane	1
azurophil granule	1
pigment granule	1
extracellular vesicle	1
endosomal intralumenal vesicle	1
lytic vacuole	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	mutant phenotype
cell-matrix adhesion	BP	mutant phenotype
endosome to melanosome transport	BP	mutant phenotype
pigment granule maturation	BP	mutant phenotype
positive regulation of integrin-mediated signaling pathway	BP	mutant phenotype
positive regulation of receptor internalization	BP	mutant phenotype
regulation of potassium ion transmembrane transport	BP	direct assay
regulation of vascular endothelial growth factor signaling pathway	BP	mutant phenotype
cell surface	CC	direct assay
endosome lumen	CC	direct assay
endosome membrane	CC	direct assay
extracellular exosome	CC	direct assay
late endosome membrane	CC	direct assay
lysosomal membrane	CC	direct assay
multivesicular body membrane	CC	direct assay
multivesicular body, internal vesicle	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 3,660 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD63	TSG101	Q99816	942
CD63	LAMP1	P11279	902
CD63	LAMP2	P13473	894
CD63	CANX	P27824	844
CD63	SDCBP2	Q9H190	803
CD63	FLOT1	O75955	784
CD63	SDCBP	O00560	776
CD63	HSPA4	P34932	759
CD63	CD81	P18582	745
CD63	RAB27A	P51159	735
CD63	PDCD6IP	Q8WUM4	734
CD63	ENPP3	O14638	720
CD63	SELP	P16109	718
CD63	EEA1	Q15075	716
CD63	LAPTM5	Q13571	715

IntAct

Human interaction partners of CD63 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
TIMP1	physical association	0.690	8
TMEM80	physical association	0.560	3
LGALS8	association	0.530	1
SLC5A9	association	0.530	1
WLS	physical association	0.490	3
LMP1	colocalization	0.460	3
ITGB1	physical association	0.460	2
SRC	physical association	0.400	1
E6	physical association	0.370	1
F2RL1	physical association	0.370	1
PROM1	physical association	0.370	1
TSC1	physical association	0.370	1
ABCC4	association	0.350	1
CYP2A13	association	0.350	1
MBLAC2	association	0.350	1
SLC5A1	association	0.350	1
TM4SF18	association	0.350	1
TMEM208	association	0.350	1

BioGRID (142 interactions; top human partners by supporting records): LGALS8 (Affinity Capture-MS; 4 records), TIMP1 (Affinity Capture-Western; 4 records), FAM134C (Affinity Capture-MS; 3 records), ITGB1 (Affinity Capture-Western; 3 records), LGALS3 (Affinity Capture-MS; 3 records), LGALS9 (Affinity Capture-MS; 3 records), RNF13 (Affinity Capture-MS; 3 records), CD82 (Affinity Capture-Western; 2 records), CD9 (Affinity Capture-Western; 2 records), KIT (Affinity Capture-Western; 2 records), PSMD12 (Co-localization; 2 records), SDCBP (Reconstituted Complex; 2 records), SLC5A9 (Affinity Capture-MS; 2 records), TSPAN2 (Affinity Capture-MS; 2 records), ABCC4 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
TFE3	“up-regulates quantity by expression”	CD63	“transcriptional regulation”

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ ITGAM-ITGB2-CD11 complex	3	CD63, ITGAM, ITGB2
★ ITGA3-ITGB1-CD63 complex	3	CD63, ITGA3, ITGB1
★ ITGA4-ITGB1-CD63 complex	3	CD63, ITGA4, ITGB1
CD63-PDCD6IP-SDCBP complex	3	SDCBP, CD63, PDCD6IP
CD63-syntenin-1 complex	2	CD63, SDCBP

Disease & clinical

Genetic variants

Variant evidence for CD63: 42 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	4
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 343):

Position(s)	Effect	Δscore	Sites
12:55725627	acceptor_loss	1.0000
12:55725639	acceptor_gain	1.0000
12:55725811–55725812	donor_loss	1.0000	4
12:55725897	acceptor_gain	1.0000
12:55725897–55725898	acceptor_loss	1.0000	5
12:55725903	acceptor_gain	1.0000
12:55725908	acceptor_gain	1.0000
12:55725914	acceptor_gain	1.0000
12:55726119–55726120	donor_loss	1.0000	4
12:55726262–55726263	acceptor_loss	1.0000	6

AlphaMissense

454 missense substitutions predicted likely pathogenic (of 1,565 scored), across 153 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D153	8	0.837	0.937
W154	7	0.984	0.999
C169	7	0.983	0.991
C146	7	0.978	0.990
C170	7	0.977	0.993
C145	7	0.969	0.987
C177	7	0.963	0.983
C191	7	0.963	0.982
F86	7	0.896	0.980
D137	7	0.885	0.932
F143	7	0.855	0.907
F107	7	0.781	0.861
D167	7	0.769	0.858
G147	6	0.972	0.989
P166	6	0.921	0.970
Q140	6	0.907	0.969
G178	6	0.881	0.967
G190	6	0.862	0.977
E217	6	0.810	0.941
F223	6	0.713	0.816

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.81e-06
Rectum Adenocarcinoma (TCGA)	unfavorable	0.000136
Glioblastoma Multiforme (validation)	unfavorable	0.000736

Disease associations

OMIM: gene MIM:155740 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST010002_69	Refractive error	6e-174
GCST003219_32	Advanced age-related macular degeneration	4e-9
GCST008310_10	Cardiac Troponin-T levels	3e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0005043	cardiac troponin T measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713303 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 418 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL5083772	BIIB-091	2	92
CHEMBL3986824	LANRAPLENIB	2	326

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

13 measured of 13 human assays (13 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-(6-amino-5-methylpyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	6.2 nM	US-9504684: Syk inhibitors
2-(5-((6-(6-amino-5-methylpyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-(4-(oxetan-3-yl)piperazin-1-yl)phenoxy)ethanol	IC50	8.7 nM	US-9504684: Syk inhibitors
2-(5-((6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)amino)-2-(4-(oxetan-3-yl)piperazin-1-yl)phenoxy)ethanol	IC50	12.2 nM	US-9504684: Syk inhibitors
6-(6-aminopyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	13.5 nM	US-9504684: Syk inhibitors
2-((4-(4-((6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)amino)phenyl)piperazin-1-yl)methyl)propane-1,3-diol	IC50	14.5 nM	US-9504684: Syk inhibitors
6-(5-amino-6-methyl-3-pyridinyl)-N-(4-morpholin-4-ylphenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	16 nM	US-9504684: Syk inhibitors
6-(5-amino-3-pyridinyl)-N-(4-morpholin-4-ylphenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	31 nM	US-9504684: Syk inhibitors
[(2R)-4-[4-[[6-(6-aminopyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl]amino]phenyl]morpholin-2-yl]methanol	IC50	33 nM	US-9290505: Substituted imidazo[1,2-a]pyrazines as Syk inhibitors
6-(6-aminopyrazin-2-yl)-5-methyl-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	44 nM	US-9504684: Syk inhibitors
6-(6-amino-3-pyridinyl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	53 nM	US-9504684: Syk inhibitors
6-(3-aminophenyl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine	IC50	188 nM	US-9504684: Syk inhibitors
(R)-1-(tert-butyl)-N-(8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-(oxetan-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1H-1,2,3-triazole-4-carboxamide	KD	660 nM
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

12 potent at pChembl≥5 of 14 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	IC50	33	nM	CHEMBL3953841
7.29	IC50	51	nM	CHEMBL3917084
7.10	IC50	80	nM	LANRAPLENIB
7.09	IC50	82	nM	BIIB-091
7.00	IC50	101	nM	CHEMBL3978560
6.92	IC50	120	nM	CHEMBL3902654
6.89	IC50	128	nM	CHEMBL3973635
6.80	IC50	157	nM	CHEMBL3929647
6.78	IC50	167	nM	CHEMBL3911668
6.60	IC50	250	nM	CHEMBL3952825
6.13	IC50	734	nM	CHEMBL3962740
6.09	IC50	809	nM	CHEMBL3981576

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820597: Inhibition of CD63 (unknown origin) assessed as FcepsilonR induced basophil activation	ic50	0.0820	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression, affects expression	4
bisphenol A	increases expression, affects expression, decreases expression	3
Tetrachlorodibenzodioxin	decreases reaction, increases expression	3
sodium arsenite	affects expression, increases expression	2
N-Formylmethionine Leucyl-Phenylalanine	increases expression, increases reaction, affects reaction, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	affects reaction, increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
bisphenol F	increases expression	1
fenebrutinib	decreases expression	1
TAK-243	increases sumoylation	1
evobrutinib	decreases expression	1
remibrutinib	decreases expression	1
orelabrutinib	decreases expression	1
rilzabrutinib	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
beta-lapachone	increases expression	1
cupric chloride	decreases expression	1
ceric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
yessotoxin	increases expression	1
SB 203580	decreases reaction, increases expression, increases reaction	1
chloropicrin	decreases expression	1
K 7174	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3887150	Binding	High Throughput Syk Biochemical Assay: Syk activity was measured using KinEASE (Cisbio), a time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay. In this assay, Syk-catalyzes the phosphorylation of a XL665-labeled pepti	Substituted imidazo[1,2-a]pyrazines as Syk inhibitors

Cellosaurus cell lines

11 cell lines: 6 transformed cell line, 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8RY	CAP-CD63-tGFP	Transformed cell line
CVCL_A8SA	CAP-CD63-tGFP-Null	Transformed cell line
CVCL_A8SC	CAP-CD63-tGFP-miRNA-493	Transformed cell line
CVCL_A8SD	CAP-CD63-tGFP-miRNA-744	Transformed cell line
CVCL_B0ZK	Abcam Hep-G2 CD63 KO	Cancer cell line	Male
CVCL_D7M7	Ubigene A-549 CD63 KO	Cancer cell line	Male
CVCL_D9BI	Ubigene HEK293 CD63 KO	Transformed cell line	Female
CVCL_D9ZQ	Ubigene HeLa CD63 KO	Cancer cell line	Female
CVCL_F6J1	EDITGENE CD63 Knockout THP-1 Cell Line	Cancer cell line	Male
CVCL_SH90	HAP1 CD63 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CD63 across ~30M SureChEMBL compounds — explore on Sugi Predict.