CD82

Summary

CD82 (CD82 molecule, HGNC:6210) is a protein-coding gene on chromosome 11p11.2, encoding CD82 antigen (P27701). Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

This metastasis suppressor gene product is a membrane glycoprotein that is a member of the transmembrane 4 superfamily. Expression of this gene has been shown to be downregulated in tumor progression of human cancers and can be activated by p53 through a consensus binding sequence in the promoter. Its expression and that of p53 are strongly correlated, and the loss of expression of these two proteins is associated with poor survival for prostate cancer patients. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 3732 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 63 total — 1 pathogenic
• GTEx eGene: eQTL in 26 tissues, sQTL in 21 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.22 (unconstrained)
• MANE Select transcript: NM_002231
• Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6210
Approved symbol	CD82
Name	CD82 molecule
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	R2, IA4, TSPAN27
Ensembl gene	ENSG00000085117
Ensembl biotype	protein_coding
OMIM	600623
Entrez	3732

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 53 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000227155

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

ENST00000227155, ENST00000342935, ENST00000524704, ENST00000524750, ENST00000525210, ENST00000525813, ENST00000525898, ENST00000526958, ENST00000527737, ENST00000529277, ENST00000529853, ENST00000530601, ENST00000530931, ENST00000532544, ENST00000878563, ENST00000878564, ENST00000878565, ENST00000878566, ENST00000878567, ENST00000878568, ENST00000878569, ENST00000878570, ENST00000878571, ENST00000878572, ENST00000878573, ENST00000878574, ENST00000878575, ENST00000878576, ENST00000878577, ENST00000878578, ENST00000878579, ENST00000878580, ENST00000878581, ENST00000878582, ENST00000925718, ENST00000925719, ENST00000925720, ENST00000968150, ENST00000968151, ENST00000968152, ENST00000968153, ENST00000968154, ENST00000968155, ENST00000968156, ENST00000968157, ENST00000968158, ENST00000968159, ENST00000968160, ENST00000968161, ENST00000968162, ENST00000968163, ENST00000968164, ENST00000968165, ENST00000968166, ENST00000968167, ENST00000968168, ENST00001041438, ENST00001041439, ENST00001041440, ENST00001041443, ENST00001118319, ENST00001143765

RefSeq mRNA: 2 — MANE Select: NM_002231 NM_001024844, NM_002231

CCDS: CCDS31469, CCDS7909

Canonical transcript exons

ENST00000227155 — 10 exons

Exon	Start	End
ENSE00002160477	44619049	44620358
ENSE00002175077	44565663	44565736
ENSE00003499197	44600158	44600230
ENSE00003517633	44587475	44587556
ENSE00003568382	44618162	44618365
ENSE00003572021	44605355	44605429
ENSE00003576897	44618640	44618723
ENSE00003597494	44605058	44605182
ENSE00003627135	44615272	44615373
ENSE00003688271	44594643	44594725

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.9068 / max 1362.5261, expressed in 1740 samples.

Highest expression (Bgee): olfactory bulb, type B pancreatic cell, esophagus mucosa, upper lobe of left lung, lymph node.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD82 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Visceral Omentum	eqtl	1.6e-36	+0.57	11:44570719:TTTA:T
Lung	sqtl	5.4e-32	+0.67	11:44618718:A:G
Esophagus Mucosa	sqtl	7.3e-31	+0.65	11:44618718:A:G
Whole Blood	sqtl	1.1e-27	+0.41	11:44618718:A:G
Esophagus Mucosa	eqtl	8.3e-23	+0.24	11:44564383:T:C
Adipose Subcutaneous	eqtl	7.8e-20	+0.42	11:44570719:TTTA:T
Cells Cultured fibroblasts	sqtl	1.4e-14	+0.47	11:44618718:A:G
Brain Hippocampus	eqtl	5.7e-14	+0.60	11:44614997:G:A
Nerve Tibial	sqtl	2.6e-13	-0.50	11:44618718:A:G
Adipose Visceral Omentum	sqtl	1.2e-12	+0.49	11:44618718:A:G
Artery Tibial	sqtl	1.7e-11	-0.48	11:44618718:A:G
Brain Putamen basal ganglia	eqtl	1.8e-11	+0.56	11:44614997:G:A
Skin Sun Exposed Lower leg	eqtl	3.5e-11	+0.16	11:44569179:G:A
Breast Mammary Tissue	eqtl	5.9e-11	+0.35	11:44570719:TTTA:T
Pancreas	eqtl	7.9e-10	-0.33	11:44569179:G:A
Brain Frontal Cortex BA9	eqtl	4.8e-09	+0.41	11:44596199:G:A
Brain Caudate basal ganglia	eqtl	5.5e-09	+0.46	11:44614997:G:A
Breast Mammary Tissue	sqtl	3.9e-08	+0.42	11:44618718:A:G
Skin Not Sun Exposed Suprapubic	eqtl	3.9e-07	+0.16	11:44569179:G:A
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-06	+0.34	11:44611404:T:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
113999	37.6345	1658
113998	16.3761	1547
206263	1.9106	1014
206264	0.4297	224
206262	0.3498	154
114005	0.2061	27

Top tissues by expression

showing 100 of 276 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	98.05	silver quality
type B pancreatic cell	CL:0000169	97.81	gold quality
esophagus mucosa	UBERON:0002469	97.27	gold quality
upper lobe of left lung	UBERON:0008952	97.19	gold quality
lymph node	UBERON:0000029	96.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.69	gold quality
right lung	UBERON:0002167	96.52	gold quality
skin of abdomen	UBERON:0001416	96.27	gold quality
upper lobe of lung	UBERON:0008948	96.27	gold quality
gall bladder	UBERON:0002110	96.26	gold quality
tongue squamous epithelium	UBERON:0006919	96.18	silver quality
diaphragm	UBERON:0001103	96.13	silver quality
skin of leg	UBERON:0001511	96.08	gold quality
minor salivary gland	UBERON:0001830	95.85	gold quality
saliva-secreting gland	UBERON:0001044	95.74	gold quality
trachea	UBERON:0003126	95.64	gold quality
cervix squamous epithelium	UBERON:0006922	95.63	gold quality
pharyngeal mucosa	UBERON:0000355	95.46	gold quality
mouth mucosa	UBERON:0003729	95.43	gold quality
vermiform appendix	UBERON:0001154	95.41	gold quality
caecum	UBERON:0001153	95.36	gold quality
nipple	UBERON:0002030	95.16	gold quality
superior surface of tongue	UBERON:0007371	95.13	gold quality
tonsil	UBERON:0002372	95.10	gold quality
decidua	UBERON:0002450	95.08	gold quality
blood	UBERON:0000178	95.04	gold quality
nasal cavity epithelium	UBERON:0005384	94.93	gold quality
tongue	UBERON:0001723	94.86	gold quality
cartilage tissue	UBERON:0002418	94.86	gold quality
right uterine tube	UBERON:0001302	94.64	gold quality
popliteal artery	UBERON:0002250	94.45	gold quality
tibial artery	UBERON:0007610	94.44	gold quality
zone of skin	UBERON:0000014	94.42	gold quality
body of tongue	UBERON:0011876	94.42	gold quality
stromal cell of endometrium	CL:0002255	94.31	gold quality
nasal cavity mucosa	UBERON:0001826	94.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.21	silver quality
vena cava	UBERON:0004087	94.14	gold quality
bone marrow cell	CL:0002092	93.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.86	gold quality
cervix epithelium	UBERON:0004801	93.80	gold quality
pylorus	UBERON:0001166	93.75	gold quality
small intestine	UBERON:0002108	93.66	gold quality
subthalamic nucleus	UBERON:0001906	93.54	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.51	gold quality
inferior vagus X ganglion	UBERON:0005363	93.51	gold quality
cardia of stomach	UBERON:0001162	93.48	gold quality
duodenum	UBERON:0002114	93.48	gold quality
ventral tegmental area	UBERON:0002691	93.43	gold quality
parotid gland	UBERON:0001831	93.14	gold quality
esophagus	UBERON:0001043	93.13	gold quality
lateral globus pallidus	UBERON:0002476	93.12	gold quality
apex of heart	UBERON:0002098	93.08	gold quality
spleen	UBERON:0002106	93.03	gold quality
body of stomach	UBERON:0001161	92.90	gold quality
granulocyte	CL:0000094	92.87	gold quality
vagina	UBERON:0000996	92.78	gold quality
bone marrow	UBERON:0002371	92.72	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.67	gold quality
thymus	UBERON:0002370	92.61	gold quality
descending thoracic aorta	UBERON:0002345	92.51	gold quality
aorta	UBERON:0000947	92.47	gold quality
monocyte	CL:0000576	92.44	gold quality
renal medulla	UBERON:0000362	92.26	gold quality
leukocyte	CL:0000738	92.24	gold quality
lower esophagus mucosa	UBERON:0035834	92.24	gold quality
islet of Langerhans	UBERON:0000006	92.13	gold quality
substantia nigra pars compacta	UBERON:0001965	92.13	gold quality
mononuclear cell	CL:0000842	92.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.10	gold quality
amygdala	UBERON:0001876	92.08	gold quality
superior vestibular nucleus	UBERON:0007227	92.08	gold quality
oocyte	CL:0000023	92.01	gold quality
stomach	UBERON:0000945	91.87	gold quality
squamous epithelium	UBERON:0006914	91.83	gold quality
right coronary artery	UBERON:0001625	91.79	gold quality
hair follicle	UBERON:0002073	91.67	silver quality
mucosa of urinary bladder	UBERON:0001259	91.62	gold quality
dorsal root ganglion	UBERON:0000044	91.54	gold quality
pericardium	UBERON:0002407	91.40	silver quality
putamen	UBERON:0001874	91.38	gold quality
mammalian vulva	UBERON:0000997	91.37	gold quality
midbrain	UBERON:0001891	91.36	gold quality
penis	UBERON:0000989	91.35	gold quality
lung	UBERON:0002048	91.28	gold quality
gingiva	UBERON:0001828	91.27	gold quality
uterine cervix	UBERON:0000002	91.25	gold quality
epithelium of esophagus	UBERON:0001976	91.24	gold quality
substantia nigra	UBERON:0002038	91.17	gold quality
trigeminal ganglion	UBERON:0001675	91.13	gold quality
fallopian tube	UBERON:0003889	91.11	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.09	silver quality
coronary artery	UBERON:0001621	91.08	gold quality
triceps brachii	UBERON:0001509	91.03	silver quality
left coronary artery	UBERON:0001626	91.02	gold quality
pons	UBERON:0000988	91.00	silver quality
gingival epithelium	UBERON:0001949	90.85	gold quality
palpebral conjunctiva	UBERON:0001812	90.82	gold quality
fundus of stomach	UBERON:0001160	90.78	gold quality
gluteal muscle	UBERON:0002000	90.55	silver quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	404.64
E-HCAD-6	yes	43.73
E-CURD-122	yes	20.65
E-GEOD-93593	yes	15.25
E-MTAB-10042	yes	14.25
E-MTAB-9067	yes	11.80
E-MTAB-6701	yes	11.79
E-CURD-112	yes	10.74
E-MTAB-9801	yes	7.14
E-GEOD-130148	yes	6.96
E-HCAD-23	no	1189.90
E-MTAB-7606	no	624.77
E-MTAB-6911	no	272.75
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	132.2	not detected
Esophagus	tissue	120.1	medium
Choroid plexus	tissue	87.0
Locus coeruleus	tissue	79.4
Tonsil	tissue	77.0	medium
Small intestine	tissue	76.6	not detected
Salivary gland	tissue	76.0	low
Duodenum	tissue	69.5	not detected
Nucleus accumbens	tissue	68.5
Vagina	tissue	68.4	not detected
Seminal vesicle	tissue	67.9	not detected
Hippocampus	tissue	64.2	not detected
Lymph node	tissue	63.8	medium
Skin 1	tissue	62.6	medium
Stomach 1	tissue	59.1	not detected
Appendix	tissue	53.9	medium
Fallopian tube	tissue	50.7	low
Lung	tissue	50.6	not detected
Caudate putamen	tissue	44.5
Urinary bladder	tissue	44.4	not detected
Spleen	tissue	44.4	not detected
Thymus	tissue	41.8
Placenta	tissue	38.4	high
Gallbladder	tissue	37.0	not detected
Adipose tissue	tissue	36.8	not detected
Liver	tissue	34.4	not detected
Breast	tissue	34.1	low
Spinal cord	tissue	33.8
Corpus callosum	tissue	33.4
Cervix	tissue	33.0	low
Superior colliculi	tissue	30.8
Postcentral gyrus	tissue	30.5
Epididymis	tissue	29.9	not detected
Pancreas	tissue	29.3	medium
Substantia nigra	tissue	26.4
Prostate	tissue	25.8	not detected
Medulla oblongata	tissue	25.6
Colon	tissue	23.1	not detected
Midbrain	tissue	22.5
Thalamus	tissue	21.9
Thyroid gland	tissue	20.9	not detected
Pons	tissue	20.4
Periaqueductal gray	tissue	19.3
Tongue	tissue	18.5
Frontal cortex	tissue	17.8
Ovary	tissue	17.2	not detected
Heart muscle	tissue	16.7	not detected
Skeletal muscle	tissue	16.6	not detected
Hypothalamus	tissue	16.5
Kidney	tissue	16.3	medium
Rectum	tissue	16.1	not detected
Putamen	tissue	16.0
Ventral forebrain	tissue	16.0
Smooth muscle	tissue	15.4	not detected
Hippocampal formation	tissue	14.4
Septum	tissue	13.5
Cerebral cortex	tissue	12.0	low
Motor cortex	tissue	12.0
Somatosensory cortex	tissue	11.7
Retrosplenial cortex	tissue	11.7

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Anterior thalamic nucleus, ventral (157.4), Globus pallidus, externus (151.7), Red nucleus (140.3), Globus pallidus, internus (128.4), Temporal white matter (123.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF3, EGR1, FOXC1, GLI3, HDAC1, HNF4A, JUN, JUNB, KAT5, NFKB, PITX2, SP1, SPRY4, TFAP2A, TP53

miRNA regulators (miRDB)

Targeting CD82 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-1343-5P	96.48	66.06	1506

Functional genomics

gnomAD constraint: pLI 1.26e-09, LOEUF 1.22, missense Z 0.146 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000227155 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 40)

• An amplification loop, via Vav and SLP76 phosphorylation and Rho-GTPase activation, is initiated by CD82 association with the cytoskeleton, thus permitting cytoskeletal rearrangement and costimulatory activity in T cells. (PMID:11839793)
• Loss of KAII is associated with primary tumos with lymph node metastasis (PMID:11895916)
• Evidence for distinctive signaling of CD82- and beta1 integrin-mediated costimulation at the transcriptional level of IL-2 gene. (PMID:11981820)
• relationship between expression, mrna levels and p53 in human bladder and prostate cancer cell lines. (PMID:12474542)
• downregulation of CD82 antigen is associated with breast tumor progression (PMID:12579280)
• KAI1 induces homotypic aggregation of human prostatic neoplasm cells through Src-dependent pathway. (PMID:12642901)
• KAI1 expression is down-regulated in advanced endometrial cancer (PMID:12684410)
• Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration in a metastatic prostate cancer cell line. (PMID:12738793)
• KAI1 down-regulation is significantly related to the progression of papillary carcinoma, including lymph node metastasis, and its anaplastic transformation. (PMID:12747469)
• EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. (PMID:12750295)
• The abnormal expression of KAI1 participates in malignant progression of colorectal cancer. (PMID:12753720)
• KAI1 is a tumor metastasis suppressor gene in digestive tract carcinomas and cancer cells. (PMID:12955496)
• CD82 regulates compartmentalisation of the EGF receptor (PMID:14576349)
• Decreased expression of KAI1 was associated with the degree of invasiveness and progression of the cancer and was an independent prognostic factor of recurrence in primary pTa and pT1 urothelial bladder carcinoma. (PMID:14706010)
• Sense and antisense genes had no significant effects on cell growth and cell cycles. Sense KAI1 gene decreased invasive ability and decreased mitochondria. Clone formation and invasive ability increased after transfection with antisense KAI1 gene. (PMID:15237426)
• KAI1 is highly related to the metastasis of colonic carcinoma and may be a useful indicator of metastasis in colonic carcinoma. (PMID:15259074)
• CD82 may serve as a prognostic marker of metastasis in thyroid cancer (PMID:15375577)
• CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes (PMID:15454569)
• CD82 attenuates integrin alpha6 signaling during a cellular morphogenic process (PMID:15557282)
• Our investigations revealed significantly reduced mRNA expression of metastases suppressor gene KAI1 in breast cancer brain metastasis. (PMID:15592684)
• urokinase receptor proteolytic function is regulated by the tetraspanin CD82 (PMID:15677461)
• The decrease of KAI1 mRNA expression may be related to lymph node metastasis and lew differentiation of larynjeal squamous cell carcinoma. (PMID:15996322)
• findings have shown that HTLV-1 Gag associates with CD82-enriched plasma membrane microdomains in Jurkat T cells (PMID:16325219)
• KAI1/CD82 over-expression in non-small cell lung carcinoma cells suppresses tumor invasiveness and metastatic potential by inducing matrix metalloproteinase-9 inactivation via up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1). (PMID:16488391)
• The expression of CD82 was closely correlated with lymph node metastasis in laryngeal carcinoma. (PMID:16494006)
• REVIEW. The SUMOylation status of the reptin chromatin-remodeling complex modulates the KAI1 metastasis suppressor gene and the invasive activity of cancer cells with metastatic potential. (PMID:16861889)
• Association of HTLV-1 Gag protein with tetraspanin-enriched microdomains is mediated by the inner loops of CD82 and CD81. (PMID:17166843)
• the expression of KAI1 in decidual cells at the human maternal-fetal interface, where the metastasis suppressor might participate in intercellular communication with trophoblast cells and the control of trophoblast invasion (PMID:17200188)
• glycosphingolipids, particularly GM2, form a complex with CD82, and this complex interacts with Met and thereby inhibits HGF-induced Met tyrosine kinase activity, as well as integrin to Met cross-talk (PMID:17215249)
• The expressions of KAI1, nm23, ETS-1 and VEGF proteins were highly related to microvascular density, cervical lymph node metastasis, and prognosis of nasopharyngeal carcinoma. (PMID:17283532)
• Expression of KAI1 in transitional cell carcinoma bladder is reported. (PMID:17393117)
• Expressions of Kiss-1 and KAI-1 mRNA in gastric cancer tissue were significantly lower than those in pericancerous tissue. (PMID:17520389)
• support a model in which KAI1/CD82 attenuates the maturation of the beta1 integrin precursor and thereby suppresses cell migration (PMID:17560548)
• CD82-c-Met complex inhibits hepatocyte growth factor-induced cancer cell migration by the inactivation of small GTP-binding proteins of the Rho family via c-Met adapter proteins (PMID:17621632)
• KAI1 gene could affect the growth pattern and proliferation of MHCC97-H cells, suppress sICAM-1 secretion and E-cadherin production, and inhibit adhesion of MHCC97-H cells. (PMID:17672940)
• Low levels of an alternatively spliced form of KAI1 mRNA are present in most bladder cancer tumours and tumour cell lines, but are not associated with invasive behaviour. (PMID:17982617)
• KAI1 gene functioned as a metastasis inhibitor by regulating the HCC cell biophysical behaviours including aggregation, adhesion, motility and visco-elastic properties. (PMID:18028322)
• gp78 promotes sarcoma metastasis by targeting KAI1 for degradation (PMID:18037895)
• a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway (PMID:18272501)
• Decreased KAI1/CD82 expression is associated with tumour progression, development of metastases and disease-specific death in penile squamous cell carcinomas. (PMID:18305955)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd82a	ENSDARG00000019098
danio_rerio	cd82b	ENSDARG00000026070
mus_musculus	Cd82	ENSMUSG00000027215
rattus_norvegicus	Cd82	ENSRNOG00000000047

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104651) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased neutrophil cell number	1
abnormal response to cardiac infarction	1
increased susceptibility to bacterial infection	1
abnormal neutrophil physiology	1
abnormal vascular endothelial cell migration	1
increased macrophage cell number	1
increased angiogenesis	1
abnormal macrophage differentiation	1
abnormal induced retina neovascularization	1
abnormal cellular extravasation	1
abnormal tumor vascularization	1
increased susceptilbility to retina ischemic injury	1
impaired leukocyte tethering or rolling	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
Pan troglodytes	P60034	100.0%	Diamond
Bos taurus	Q17QJ5	99.6%	Diamond
Pongo abelii	Q5RAP3	99.2%	Diamond
Chlorocebus aethiops	P30409	99.1%	Diamond
Saguinus oedipus	Q9N0J9	97.9%	Diamond
Sus scrofa	Q06AA5	97.1%	Diamond
Felis catus	P40239	91.2%	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
LINC02704	ncRNA	105376647
TSPAN18-AS1	ncRNA	115253419
CD82-AS1	ncRNA	126568847
TSPAN18	protein-coding	90139
ALX4	protein-coding	60529

Protein

Protein identifiers

CD82 antigen — P27701 (reviewed: P27701)

Alternative names: C33 antigen, IA4, Inducible membrane protein R2, Metastasis suppressor Kangai-1, Suppressor of tumorigenicity 6 protein, Tetraspanin-27

All UniProt accessions (9): E9PJ45, E9PJ59, E9PJB7, E9PJC7, E9PJK9, E9PM43, E9PP61, P27701, H0YD57

UniProt curated annotations — full annotation on UniProt →

Function. Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Participates thereby in diverse biological functions such as cell signal transduction, adhesion, migration and protein trafficking. Acts as a attenuator of EGF signaling, facilitating ligand-induced endocytosis of the receptor and its subsequent desensitization. Mechanistically, modulates ligand-induced ubiquitination and trafficking of EGFR via E3 ligase CBL phosphorylation by PKC. Increases cell-matrix adhesion by regulating the membrane organization of integrin alpha4/ITA4. Modulates adhesion and suppresses cell migration through other integrins such as the alpha6/ITGA6 and beta1/ITGB1. Decreases cell-associated plasminogen activation by interfering with the interaction between urokinase-type plasminogen activator/PLAU and its receptor PLAUR. Associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway. Plays a role in TLR9 trafficking to acidified CpG-containing compartments by controlling interaction between TLR9 and VAMP3 and subsequent myddosome assembly. Inhibits LPS-induced inflammatory response by preventing binding of LPS to TLR4 on the cell surface. Plays a role in the activation of macrophages into anti-inflammatory phenotypes. Independently of Toll-like receptor (TLR) signaling, is recruited to pathogen-containing phagosomes prior to fusion with lysosomes and thereby participates in antigen presentation. Also acts to control angiogenesis and switch angiogenic milieu to quiescent state by binding and sequestering VEGFA and PDGFB to inhibit the signaling they trigger via their respective cell surface receptor.

Subunit / interactions. Forms homooligomers. Interacts directly with IGSF8. Interacts with EGFR. Interacts with VEGFA and PDGFB. Interacts with ITGA4. Interacts with ITGA6; this interaction reduces ITGA6 cell surface expression. Interacts with ITGB1. Interacts with TLR4; this interaction inhibits TLR4-mediated signaling pathway. Interacts with TLR9. Interacts with PLAUR.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Phagosome.

Tissue specificity. Lymphoid specific.

Post-translational modifications. Palmitoylated. Palmitoylation contributes to oligomerization and surface expression.

Similarity. Belongs to the tetraspanin (TM4SF) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P27701-1	1	yes
P27701-2	2

RefSeq proteins (2): NP_001020015, NP_002222* (*=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 (21 total): topological domain 5, transmembrane region 4, glycosylation site 3, lipid moiety-binding region 2, mutagenesis site 2, sequence conflict 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
9HT6	Crystal structure of Tetraspanin CD82 Large Extracellular Loop (LEL)	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27701-F1	88.31	0.65

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF uncertain

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 (2)

Type	Positions
S-palmitoyl cysteine	5, 74

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	129, 157, 198

Mutagenesis-validated functional residues (2)

Position	Phenotype
5	strong decrease in the expressions of cd82 and egfr on the cell membrane; when associated with s-74.
74	strong decrease in the expressions of cd82 and egfr on the cell membrane; when associated with s-5.

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 251 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, LEE_NEURAL_CREST_STEM_CELL_DN, MODULE_64, NF1_Q6_01, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, SANSOM_APC_TARGETS_DN, PID_P53_DOWNSTREAM_PATHWAY, LANDIS_ERBB2_BREAST_PRENEOPLASTIC_UP, ONDER_CDH1_SIGNALING_VIA_CTNNB1, MOREIRA_RESPONSE_TO_TSA_UP, DELASERNA_MYOD_TARGETS_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, RODRIGUES_DCC_TARGETS_DN, JOSEPH_RESPONSE_TO_SODIUM_BUTYRATE_UP, SHEN_SMARCA2_TARGETS_DN

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

GO Cellular Component (5): plasma membrane (GO:0005886), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

8 GO namespaces:

Category	Terms
binding	1
membrane	1
cell periphery	1
endocytic vesicle	1
extracellular vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 6 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,382 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD82	TPMT	P51580	797
CD82	TSG101	Q99816	775
CD82	APBB1	O00213	753
CD82	KAT5	Q92993	676
CD82	SERF1A	O75920	652
CD82	DENND2B	P78523	646
CD82	B4E171	B4E171	623
CD82	AMFR	P26442	618
CD82	TAB2	Q9NYJ8	617
CD82	ACKR1	Q16570	615
CD82	CTNNB1	P35222	612
CD82	TMSB15A	P0CG34	601
CD82	SDCBP	O00560	595
CD82	BACE1	P56817	592
CD82	APP	P05067	588

IntAct

Human interaction partners of CD82 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
TIMP1	direct interaction	0.600	9
FFAR2	physical association	0.560	3
KLRC1	physical association	0.560	3
SMIM3	physical association	0.560	3
VANGL1	physical association	0.540	6
BDKRB2	physical association	0.370	1
CHRM5	physical association	0.370	1
CREB3	physical association	0.370	1
CD19	proximity	0.270	1
NFKB1	proximity	0.270	1
NUP88	physical association	0.000	1

BioGRID (56 interactions; top human partners by supporting records): CD19 (Co-localization; 3 records), NLRP3 (Affinity Capture-MS; 3 records), AMFR (Affinity Capture-Western; 2 records), BRCC3 (Affinity Capture-MS; 2 records), CD63 (Affinity Capture-Western; 2 records), CD81 (Affinity Capture-Western; 2 records), CDCP1 (Affinity Capture-Western; 2 records), B3GALTL (Co-fractionation), BDKRB2 (Two-hybrid), BIRC2 (Affinity Capture-MS), CD151 (Affinity Capture-Western), CD4 (Affinity Capture-Western), CD46 (Affinity Capture-Western), CD53 (Affinity Capture-Western), CD9 (Affinity Capture-Western)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
SPRY4	“up-regulates quantity by expression”	CD82	“transcriptional regulation”
CD82	down-regulates	Cell_invasion

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ CD82-MET complex	2	CD82, MET

Disease & clinical

Genetic variants

Variant evidence for CD82: 63 ClinVar records (1 pathogenic / likely pathogenic); 20 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1340048	GRCh37/hg19 11p12-11.2(chr11:40117145-46920718)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CD82’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 900):

Position(s)	Effect	Δscore	Sites
11:44587557–44587558	donor_loss	1.0000	5
11:44600156–44600157	acceptor_loss	1.0000	6
11:44605056–44605057	acceptor_loss	1.0000	5
11:44615140	donor_gain	1.0000
11:44615267	acceptor_gain	1.0000
11:44615270–44615271	acceptor_loss	1.0000	5
11:44615374–44615375	donor_loss	1.0000	5
11:44618638–44618639	acceptor_loss	1.0000	4
11:44565737–44565738	donor_loss	0.9900	5
11:44587472–44587474	acceptor_loss	0.9900	7

AlphaMissense

592 missense substitutions predicted likely pathogenic (of 1,768 scored), across 169 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
D141	8	0.924	0.978
F41	8	0.849	0.981
D37	8	0.807	0.913
F14	8	0.793	0.957
F16	8	0.761	0.935
W158	7	0.989	0.999
C150	7	0.988	0.994
C176	7	0.984	0.993
C216	7	0.980	0.990
C149	7	0.978	0.992
C174	7	0.960	0.976
C193	7	0.951	0.971
W152	7	0.907	0.992
F192	7	0.892	0.959
N17	7	0.887	0.991
W209	7	0.887	0.987
W33	7	0.881	0.986
W223	7	0.848	0.970
F89	7	0.805	0.960
W140	6	0.977	0.993

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	1.22e-06

Disease associations

OMIM: gene MIM:600623 | disease phenotypes:

GWAS associations

20 associations:

Study	Trait	p-value
GCST004621_48	Red cell distribution width	1e-21
GCST90002386_201	High light scatter reticulocyte percentage of red cells	2e-20
GCST90002385_513	High light scatter reticulocyte count	3e-19
GCST006804_162	Red cell distribution width	6e-17
GCST90002406_349	Reticulocyte fraction of red cells	3e-15
GCST90002405_552	Reticulocyte count	5e-14
GCST90002404_534	Red cell distribution width	3e-13
GCST90002396_539	Mean reticulocyte volume	1e-12
GCST006988_125	Blond vs. brown/black hair color	3e-11
GCST004612_133	High light scatter reticulocyte percentage of red cells	7e-11
GCST004611_207	High light scatter reticulocyte count	3e-10
GCST90002404_535	Red cell distribution width	3e-10
GCST003983_28	Male-pattern baldness	6e-10
GCST90002388_176	Lymphocyte count	1e-9
GCST012436_2	TNF-alpha gene expression levels in non-alcoholic fatty liver disease x mastiha supplementation interaction	2e-8
GCST002936_20	Cadmium levels	2e-7
GCST005411_2	Thrombin-activatable fibrinolysis inhibitor activation peptide	3e-7
GCST001875_8	Pubertal anthropometrics	2e-6
GCST006431_20	Plasma parathyroid hormone levels	3e-6
GCST001378_8	Hemostatic factors and hematological phenotypes	7e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0004503	hematological measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0003924	hair color
EFO:0600067	mastiha supplement exposure measurement
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	4
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases reaction	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects localization, affects cotreatment	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
mercuric bromide	decreases expression	1
pentanal	increases expression	1
11,12-epoxy-5,8,14-eicosatrienoic acid	decreases reaction, increases expression	1
phenethyl isothiocyanate	increases expression	1
U 0126	affects expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
scriptaid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_8650	HB2/CD82	Transformed cell line	Female
CVCL_D1RV	Abcam U-87MG CD82 KO	Cancer cell line	Male
CVCL_T421	Psi-CRIP-RxhCD82	Transformed cell line	Male

Clinical trials (associated diseases)

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