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
• MANE Select transcript: NM_002231

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: 56 — 52 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

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

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.

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

276 total, 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

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

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)

25 targeting CD82, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

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)

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): P27701, E9PJ45, E9PJ59, E9PJB7, E9PJC7, E9PJK9, E9PM43, E9PP61, 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.

PDB	Method	Resolution (Å)
9HT6	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

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

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): 5, 74

Glycosylation sites (3): 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 pathways

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 Biological Process (0):

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

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD82	B4E171	B4E171	986
CD82	CD63	P08962	982
CD82	CD81	P18582	979
CD82	CD9	P21926	977
CD82	ACKR1	Q16570	973
CD82	CD4	P01730	952
CD82	VANGL1	Q8TAA9	914
CD82	CD8A	P01732	912
CD82	IGSF8	Q969P0	840
CD82	TSG101	Q99816	834
CD82	CD53	P19397	823
CD82	TPMT	P51580	793
CD82	CD37	P11049	791
CD82	APBB1	O00213	764
CD82	CTNNB1	P35222	749

IntAct

52 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TIMP1	CD63	psi-mi:“MI:0914”(association)	0.690
CD82	TIMP1	psi-mi:“MI:0407”(direct interaction)	0.600
TIMP1	CD82	psi-mi:“MI:0914”(association)	0.600
TIMP1	CD82	psi-mi:“MI:0407”(direct interaction)	0.600
CD82	TIMP1	psi-mi:“MI:0403”(colocalization)	0.600
TIMP1	CD82	psi-mi:“MI:0403”(colocalization)	0.600
KLRC1	CD82	psi-mi:“MI:0915”(physical association)	0.560
CD82	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	CD82	psi-mi:“MI:0915”(physical association)	0.560
CD82	VANGL1	psi-mi:“MI:0915”(physical association)	0.540
VANGL1	CD82	psi-mi:“MI:0915”(physical association)	0.540
CD82	VANGL1	psi-mi:“MI:0403”(colocalization)	0.540
CD82	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
CD82	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
CD82	CREB3	psi-mi:“MI:0915”(physical association)	0.370
	CD82	psi-mi:“MI:0915”(physical association)	0.370
TRAF2	UMAD1	psi-mi:“MI:0914”(association)	0.350
RBCK1	UMAD1	psi-mi:“MI:0914”(association)	0.350
TNIP1	UMAD1	psi-mi:“MI:0914”(association)	0.350
TNIP2	CHUK	psi-mi:“MI:0914”(association)	0.350
TRAF2	TMEM178B	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): CD82 (Two-hybrid), CD82 (Co-localization), CD82 (Co-localization), CD151 (Affinity Capture-Western), CD9 (Affinity Capture-Western), ERBB2 (Affinity Capture-Western), ERBB3 (Affinity Capture-Western), CD82 (Affinity Capture-Western), CD82 (Affinity Capture-MS), CD82 (Affinity Capture-MS), CD82 (Affinity Capture-MS), CD82 (Affinity Capture-MS), CD82 (Affinity Capture-MS), CD82 (Affinity Capture-MS), FFAR2 (Two-hybrid)

ESM2 similar proteins: A7PHN8, A7Q6G6, A9NMM6, B8LQF9, B9GIE4, B9RH17, C6SYW3, C6SZ04, C6TG62, C6TH93, D7KBH3, F4I214, H2L006, O00322, O42282, O42583, O46101, O70352, P0DI47, P0DI48, P19397, P27701, P38572, P40237, Q11098, Q17JQ7, Q1PDI1, Q22495, Q2KIS9, Q6NWG0, Q7PRJ0, Q84WF6, Q86UG4, Q8S8Q6, Q93XY5, Q940P5, Q9C5W7, Q9C7C1, Q9D132, Q9FIQ5

Diamond homologs: A1L157, B5X3I6, O14817, O35566, O60636, O70352, P19075, P24485, P27701, P40241, P48509, P60033, P60034, P61170, P61171, Q0VC33, Q3ZBH3, Q4V8E0, Q568Y5, Q58CY8, Q58DN3, Q5R9S6, Q5RAP3, Q61451, Q80WR1, Q8WMQ3, Q96FV3, Q96SJ8, Q9D1D1, Q9D7W4, Q9DCK3, Q9JJW1, Q9QZA6, A0A8M2B5N2, A0A8V0ZLT4, B0BM39, B3VSC2, H2L006, O75954, O97703

SIGNOR signaling

2 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
TNFR1-induced NF-kappa-B signaling pathway	5	62.2×	4e-06
Regulation of TNFR1 signaling	5	41.5×	2e-05
Innate Immune System	7	6.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	6	70.9×	7e-08
negative regulation of canonical NF-kappaB signal transduction	6	33.3×	4e-06
positive regulation of canonical NF-kappaB signal transduction	6	14.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

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)

Variant ID	HGVS	Classification
1340048	GRCh37/hg19 11p12-11.2(chr11:40117145-46920718)x1	Pathogenic

SpliceAI

1686 predictions. Top by Δscore:

Variant	Effect	Δscore
11:44587552:GGAAG:G	donor_gain	1.0000
11:44587553:GAAGG:G	donor_gain	1.0000
11:44587554:AAGGT:A	donor_loss	1.0000
11:44587555:AGG:A	donor_loss	1.0000
11:44587556:GGT:G	donor_loss	1.0000
11:44587557:G:GG	donor_gain	1.0000
11:44587557:GTA:G	donor_loss	1.0000
11:44587558:T:G	donor_loss	1.0000
11:44600152:TTCCA:T	acceptor_loss	1.0000
11:44600154:CCAG:C	acceptor_loss	1.0000
11:44600155:CA:C	acceptor_loss	1.0000
11:44600156:A:AG	acceptor_gain	1.0000
11:44600156:A:C	acceptor_loss	1.0000
11:44600157:G:GG	acceptor_gain	1.0000
11:44600229:GC:G	donor_gain	1.0000
11:44600231:G:GG	donor_gain	1.0000
11:44605053:CCTA:C	acceptor_loss	1.0000
11:44605055:TA:T	acceptor_loss	1.0000
11:44605056:A:AG	acceptor_gain	1.0000
11:44605056:A:AT	acceptor_loss	1.0000
11:44605057:G:GT	acceptor_gain	1.0000
11:44605057:GA:G	acceptor_gain	1.0000
11:44605057:GAA:G	acceptor_gain	1.0000
11:44605057:GAAA:G	acceptor_gain	1.0000
11:44605057:GAAAC:G	acceptor_gain	1.0000
11:44605353:A:AG	acceptor_gain	1.0000
11:44605354:G:GG	acceptor_gain	1.0000
11:44615140:A:T	donor_gain	1.0000
11:44615267:T:TA	acceptor_gain	1.0000
11:44615267:TGCA:T	acceptor_loss	1.0000

AlphaMissense

1768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:44618197:G:C	W158C	0.999
11:44618197:G:T	W158C	0.999
11:44618195:T:A	W158R	0.996
11:44618195:T:C	W158R	0.996
11:44618174:G:T	G151C	0.995
11:44600164:G:C	G24R	0.994
11:44618171:T:A	C150S	0.994
11:44618172:G:C	C150S	0.994
11:44615353:T:A	W140R	0.993
11:44615353:T:C	W140R	0.993
11:44618172:G:A	C150Y	0.993
11:44618175:G:T	G151V	0.993
11:44618250:G:A	C176Y	0.993
11:44605129:G:C	G70R	0.992
11:44618168:T:C	C149R	0.992
11:44618179:G:C	W152C	0.992
11:44618179:G:T	W152C	0.992
11:44594713:C:A	N17K	0.991
11:44594713:C:G	N17K	0.991
11:44600179:G:C	G29R	0.991
11:44605108:G:A	G63R	0.991
11:44605108:G:C	G63R	0.991
11:44605109:G:A	G63E	0.991
11:44618249:T:A	C176S	0.991
11:44618250:G:C	C176S	0.991
11:44600165:G:A	G24D	0.990
11:44605108:G:T	G63W	0.990
11:44618168:T:A	C149S	0.990
11:44618169:G:C	C149S	0.990
11:44618170:C:G	C149W	0.990

dbSNP variants (sampled 300 via entrez): RS1000000095 (11:44565674 C>G,T), RS1000024424 (11:44602264 C>T), RS1000091277 (11:44579669 T>C), RS1000106516 (11:44609252 T>G), RS1000140828 (11:44586406 T>G), RS1000193609 (11:44586579 C>A), RS1000218887 (11:44568952 C>A,T), RS1000314641 (11:44606603 G>T), RS1000375644 (11:44592216 C>T), RS1000403360 (11:44577385 T>C,G), RS1000424495 (11:44612869 G>A,C), RS1000476572 (11:44597785 C>T), RS1000502524 (11:44570055 A>G), RS1000598963 (11:44593667 A>G), RS1000604574 (11:44595909 A>AC)

Disease associations

OMIM: gene MIM:600623 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001378_8	Hemostatic factors and hematological phenotypes	7.000000e-06
GCST001875_8	Pubertal anthropometrics	2.000000e-06
GCST002936_20	Cadmium levels	2.000000e-07
GCST003983_28	Male-pattern baldness	6.000000e-10
GCST004611_178	High light scatter reticulocyte count	3.000000e-10
GCST004612_116	High light scatter reticulocyte percentage of red cells	7.000000e-11
GCST004621_23	Red cell distribution width	1.000000e-21
GCST005411_11	Thrombin-activatable fibrinolysis inhibitor activation peptide	3.000000e-07
GCST006431_20	Plasma parathyroid hormone levels	3.000000e-06
GCST006804_112	Red cell distribution width	6.000000e-17
GCST006988_86	Blond vs. brown/black hair color	3.000000e-11
GCST012436_1	TNF-alpha gene expression levels in non-alcoholic fatty liver disease x mastiha supplementation interaction	2.000000e-08
GCST90002385_200	High light scatter reticulocyte count	3.000000e-19
GCST90002386_350	High light scatter reticulocyte percentage of red cells	2.000000e-20
GCST90002388_534	Lymphocyte count	1.000000e-09
GCST90002396_464	Mean reticulocyte volume	1.000000e-12
GCST90002404_509	Red cell distribution width	3.000000e-13
GCST90002404_510	Red cell distribution width	3.000000e-10
GCST90002405_279	Reticulocyte count	5.000000e-14
GCST90002406_367	Reticulocyte fraction of red cells	3.000000e-15

EFO canonical traits (7, from GWAS)

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 (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	3
bisphenol A	decreases methylation, decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	increases reaction, affects cotreatment, decreases expression	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	affects cotreatment, decreases expression	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)

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