CD2

Summary

CD2 (CD2 molecule, HGNC:1639) is a protein-coding gene on chromosome 1p13.1, encoding T-cell surface antigen CD2 (P06729). CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types.

The protein encoded by this gene is a surface antigen found on all peripheral blood T-cells. The encoded protein interacts with LFA3 (CD58) on antigen presenting cells to optimize immune recognition. A locus control region (LCR) has been found in the 3’ flanking sequence of this gene.

Source: NCBI Gene 914 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• MANE Select transcript: NM_001767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1639
Approved symbol	CD2
Name	CD2 molecule
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116824
Ensembl biotype	protein_coding
OMIM	186990
Entrez	914

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000369477, ENST00000369478, ENST00000851329, ENST00000851330, ENST00000851331

RefSeq mRNA: 2 — MANE Select: NM_001767 NM_001328609, NM_001767

CCDS: CCDS889

Canonical transcript exons

ENST00000369478 — 5 exons

Exon	Start	End
ENSE00000785006	116754631	116754951
ENSE00000785007	116760402	116760632
ENSE00000785008	116764484	116764606
ENSE00001141790	116768464	116769229
ENSE00001450130	116754430	116754553

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.58.

FANTOM5 (CAGE): breadth broad, TPM avg 15.3717 / max 991.0433, expressed in 253 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4854	15.0074	250
4856	0.2308	60
4855	0.1335	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.58	gold quality
thymus	UBERON:0002370	96.18	gold quality
lymph node	UBERON:0000029	95.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.79	gold quality
vermiform appendix	UBERON:0001154	94.51	gold quality
blood	UBERON:0000178	94.40	gold quality
epithelium of nasopharynx	UBERON:0001951	93.91	gold quality
superficial temporal artery	UBERON:0001614	92.94	gold quality
spleen	UBERON:0002106	90.48	gold quality
ileal mucosa	UBERON:0000331	90.47	gold quality
caecum	UBERON:0001153	89.05	gold quality
jejunal mucosa	UBERON:0000399	88.15	gold quality
gall bladder	UBERON:0002110	86.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.18	gold quality
decidua	UBERON:0002450	85.69	gold quality
palpebral conjunctiva	UBERON:0001812	85.28	gold quality
rectum	UBERON:0001052	84.90	gold quality
tonsil	UBERON:0002372	84.41	gold quality
type B pancreatic cell	CL:0000169	84.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.10	silver quality
olfactory bulb	UBERON:0002264	84.06	gold quality
mucosa of urinary bladder	UBERON:0001259	83.52	gold quality
cervix squamous epithelium	UBERON:0006922	83.25	silver quality
small intestine	UBERON:0002108	83.13	gold quality
colonic epithelium	UBERON:0000397	82.61	gold quality
bone marrow	UBERON:0002371	82.26	gold quality
cervix epithelium	UBERON:0004801	82.00	gold quality
mucosa of transverse colon	UBERON:0004991	81.70	gold quality
duodenum	UBERON:0002114	81.58	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	3052.54
E-CURD-97	yes	2337.74
E-GEOD-139324	yes	1676.04
E-MTAB-8410	yes	1507.01
E-HCAD-36	yes	920.44
E-HCAD-15	yes	868.34
E-MTAB-10553	yes	825.29
E-CURD-88	yes	802.09
E-MTAB-9221	yes	773.22
E-MTAB-10287	yes	681.85
E-CURD-122	yes	666.18
E-HCAD-1	yes	651.91
E-CURD-46	yes	630.77
E-GEOD-75688	yes	614.70
E-MTAB-8142	yes	93.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, BATF, DNMT1, GATA4, GLI2, MAF, NFKB1, NFKB2, NR1H3, RUNX1, TCFL5, TP53, TXK, USF1, USF2

miRNA regulators (miRDB)

17 targeting CD2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 40)

• CD2-CD58 binding site (PMID:11575926)
• PTEN expression was up-regulated on RNA and protein level in freshly isolated human CD4(+) T cells following stimulation with CD28 or CD2. (PMID:11932928)
• molecules redistribute to the uropod during T cell scanning (PMID:12032326)
• Structural and functional studies of the extracellular domains of CD2 and CD58 and their complex. Review. (PMID:12369898)
• CD2BP2 is the ligand of the membrane-proximal proline-rich tandem repeat of CD2 in detergent-soluble membrane compartments, but is replaced by Fyn SH3 after CD2 is translocated into lipid rafts upon CD2 ectodomain clustering. (PMID:12426371)
• PSTPIP1 acts downstream of CD2/CD2AP to link CD2 engagement to the WASp-evoked actin polymerization required for synapse formation and T cell activation. (PMID:12530983)
• This T cell surface antigen is linked to the actin-capping protein CAPZ via CMS and CIN85. (PMID:12690097)
• another role of the CD2-CD58 pathway that allows nonimmune and immune cells to interact directly with dendritic cells and initiate innate and adaptive immune responses. (PMID:12714509)
• CD2 mediates activation of the IFN-gamma intronic STAT binding region in mucosal T cells. (PMID:12731040)
• CD2 mediates activation of a distal -3.6-kilobase STAT5 binding region of the interferon-gamma promoter. (PMID:15528362)
• CD48 is a CD2 and CD244 (2B4)-binding protein (PMID:16803907)
• We use this analysis to determine that the 2D Kd for CD2-CD58 is 5.4-7.6 molecules/microm2. 2D Kd analysis provides a general and quantitative measure of the mechanisms regulating cell-cell adhesion. (PMID:17085486)
• T cell activation causes the CD58-bound CD2 to be recognized and immobilized at sites of cell-cell contact, thereby strengthening T cell-APC adhesion (PMID:17168569)
• results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection (PMID:18318997)
• Data suggest that detection of CD2 or CD13 expression in chronic lymphocytic leukemia (CLL) suggests familial CLL, and that CD38 expression does not carry the negative prognosis observed in sporadic CLL. (PMID:18431797)
• the synergistic synthesis of IL-8 occurs when lymphocytes are stimulated through the CD2 pathway by CD58 on HT-29 cells, resulting in TNF-alpha release that, in turn, augments IL-8 synthesis and CD58 expression by the HT-29 cells (PMID:19109405)
• during clinical remission, increases in CD58 expression, mediated by the protective allele, up-regulate the expression of FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of TREG cells that are defective in MS (PMID:19237575)
• CD2 functions as the master switch recruiting CD48 and Lck (PMID:19494291)
• LFA-1 and CD2 synergize for the Erk1/2 activation in the Natural Killer (NK) cell immunological synapse (PMID:19502238)
• CD244 inhibition and activation depends on CD2 and phospholipase C-gamma1 (PMID:19586919)
• Genetic variants at CD2 are associated with rheumatoid arthritis risk (PMID:19898481)
• analysis of the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells (PMID:20813844)
• When isolated from multiple sclerosis patients, both nonmature and effector subsets of memory CD127(low) regulatory T cells exhibit kinetically distinct defects in suppression that are evident with CD2 pathway costimulation. (PMID:21300823)
• CD2 signals more strongly to S6-ribosomal protein, whereas CD28 costimulation specifically induces signaling necessary for proper NF-kappaB activation. (PMID:22013130)
• CD2-mediated priming of resting natural killer (NK) cells is unaffected by their degree of functional maturation. (PMID:22084431)
• CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone. (PMID:22222639)
• Aberrant CD2 expression appears to further determine a shorter progression free survival (PMID:22634534)
• CD2-CD58/48 receptor-ligand interaction promotes and is required for nanotube formation in human natural killer cells. (PMID:23112830)
• Altogether, these results show that a high CD2 expression level is a hallmark of latently infected resting memory CD4(+) T cells in vivo. (PMID:23760244)
• ERGdel may be a pure surrogate of CD2-positivity–which has been suggested to be a good prognositc marker in childhood ALL (PMID:24072102)
• Both the mRNA expression levels and protein expression levels of HSP27 were increased in astrocytes from POAG patients compared with those from normal control, suggesting that mutation in CD2 might pose a risk for POAG in Chinese population. (PMID:24597656)
• Although sMCs displayed immunoreactivity for one of the neoplastic antigens in the majority of SM patients, the aberrant CD2 and/or CD25 expression on sMCs is not as indicative of SM as the BMMC immunophenotype. (PMID:25402852)
• the fundamental mechanism of glycosylation of human CD2 is to promote CD2-CD58 binding by conformational adjustment of CD2 (PMID:25984915)
• CD58/CD2 is the primary costimulatory pathway in human CD28-CD8+ T cells. (PMID:26041540)
• These results reveal an unexpected redundancy in the human NK cell response to human cytomegalovirus and suggest that CD2 provides “signal 2” in antibody-driven adaptive NK cell responses. (PMID:27117418)
• Establish CD2 as a new susceptibility factor for systemic sclerosis in a European Caucasian population. (PMID:27385538)
• A new prognostic model for HR-/HER2+ breast cancer based on the expression of MMP11 and CD2 was developed and the distant metastasis-free survival for patients in the high-risk group according to our model was significantly lower than that for those in the low-risk group. (PMID:28409241)
• Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin. (PMID:31324882)
• Phosphoproteomics of CD2 signaling reveals AMPK-dependent regulation of lytic granule polarization in cytotoxic T cells. (PMID:32398348)
• CD2 and CD7 are sensitive flow cytometry screening markers for T-lineage acute leukemia(s): a study of 465 acute leukemia cases. (PMID:34019867)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:cabz01074946.1	ENSDARG00000090396
mus_musculus	Cd2	ENSMUSG00000027863
rattus_norvegicus	Cd2	ENSRNOG00000015821

Paralogs (9): SLAMF7 (ENSG00000026751), CD84 (ENSG00000066294), SLAMF1 (ENSG00000117090), CD48 (ENSG00000117091), CD244 (ENSG00000122223), LY9 (ENSG00000122224), SLAMF8 (ENSG00000158714), SLAMF9 (ENSG00000162723), SLAMF6 (ENSG00000162739)

Protein

Protein identifiers

T-cell surface antigen CD2 — P06729 (reviewed: P06729)

Alternative names: Erythrocyte receptor, LFA-2, LFA-3 receptor, Rosette receptor, T-cell surface antigen T11/Leu-5

All UniProt accessions (3): P06729, Q53F96, Q5JVN7

UniProt curated annotations — full annotation on UniProt →

Function. CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function.

Subunit / interactions. Interacts with CD48. Interacts with CD58 (LFA-3). Interacts with CD2AP. Interacts with PSTPIP1. Interacts with FCGR3A; this interaction modulates NK cell activation and cytotoxicity.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in natural killer cells (at protein level).

RefSeq proteins (2): NP_001315538, NP_001758* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008424	Ig_C2-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015631	CD2/SLAM_rcpt	Family
IPR015632	CD2	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF05790, PF07686

UniProt features (48 total): strand 16, mutagenesis site 4, compositionally biased region 3, glycosylation site 3, sequence variant 3, helix 3, region of interest 3, disulfide bond 2, topological domain 2, sequence conflict 2, turn 2, domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2J6O	X-RAY DIFFRACTION	2.23
1HNF	X-RAY DIFFRACTION	2.5
2J7I	X-RAY DIFFRACTION	2.9
1QA9	X-RAY DIFFRACTION	3.2
1CDB	SOLUTION NMR
1GYA	SOLUTION NMR
1L2Z	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06729-F1	78.25	0.53

Functional residue map

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

Disulfide bonds (2): 139–203, 146–186

Glycosylation sites (3): 89, 141, 150

Mutagenesis-validated functional residues (4):

Position	Phenotype
67	loss of cd58 binding.
70	loss of cd58 binding.
110	loss of cd58 and cd59 binding.
111	loss of cd58 and cd59 binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-109582	Hemostasis

MSigDB gene sets: 319 (showing top): FERRANDO_TAL1_NEIGHBORS, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, WALLACE_PROSTATE_CANCER_RACE_UP, MODULE_169, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, MODULE_45, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_MEMBRANE_RAFT_ORGANIZATION

GO Biological Process (15): membrane raft polarization (GO:0001766), apoptotic process (GO:0006915), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), natural killer cell activation (GO:0030101), positive regulation of myeloid dendritic cell activation (GO:0030887), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), heterotypic cell-cell adhesion (GO:0034113), T cell activation (GO:0042110), natural killer cell mediated cytotoxicity (GO:0042267), regulation of T cell differentiation (GO:0045580), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (6): signaling receptor binding (GO:0005102), receptor tyrosine kinase binding (GO:0030971), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), protein binding (GO:0005515), protein kinase binding (GO:0019901)

GO Cellular Component (10): extracellular region (GO:0005576), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), external side of plasma membrane (GO:0009897), cytoplasmic side of plasma membrane (GO:0009898), cell surface (GO:0009986), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
lymphocyte activation	2
positive regulation of cytokine production	2
protein binding	2
plasma membrane	2
membrane raft distribution	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
response to stimulus	1
signal transduction	1
myeloid dendritic cell activation	1
positive regulation of leukocyte activation	1
regulation of myeloid dendritic cell activation	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cell-cell adhesion	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
T cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of T cell activation	1
cell adhesion	1
cellular process	1
signaling receptor binding	1
protein tyrosine kinase binding	1
molecular transducer activity	1
binding	1
kinase binding	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1

Protein interactions and networks

STRING

2886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD2	CD58	P19256	999
CD2	CD48	P09326	997
CD2	CD8A	P01732	995
CD2	CD4	P01730	994
CD2	ICAM1	P05362	992
CD2	CD5	P06127	984
CD2	CD28	P10747	981
CD2	CD7	P09564	967
CD2	CD2BP2	O95400	958
CD2	CD59	P13987	952
CD2	CD2AP	Q9Y5K6	948
CD2	LCK	P06239	947
CD2	CD19	P15391	932
CD2	NCAM1	P13591	918
CD2	FCGR3A	P08637	899

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CD2BP2	CD2	psi-mi:“MI:0407”(direct interaction)	0.930
CD2	CD2BP2	psi-mi:“MI:0407”(direct interaction)	0.930
CD2BP2	CD2	psi-mi:“MI:0915”(physical association)	0.930
CD2	CD2BP2	psi-mi:“MI:0915”(physical association)	0.930
CD2	CD2AP	psi-mi:“MI:0915”(physical association)	0.800
CD2AP	CD2	psi-mi:“MI:0407”(direct interaction)	0.800
CD2	CD2AP	psi-mi:“MI:0407”(direct interaction)	0.800
PSTPIP1	CD2	psi-mi:“MI:0915”(physical association)	0.740
CD2	PSTPIP1	psi-mi:“MI:0915”(physical association)	0.740
PSTPIP1	CD2	psi-mi:“MI:0407”(direct interaction)	0.740
CD2	CD58	psi-mi:“MI:0915”(physical association)	0.710
CD58	CD2	psi-mi:“MI:0915”(physical association)	0.710
CD58	CD2	psi-mi:“MI:0407”(direct interaction)	0.710

BioGRID (36): SH3KBP1 (Co-crystal Structure), CD2AP (Co-crystal Structure), CD2 (Reconstituted Complex), CD2AP (Reconstituted Complex), CD2 (Reconstituted Complex), SH3KBP1 (Reconstituted Complex), SH3KBP1 (Reconstituted Complex), CD2AP (Reconstituted Complex), DNAJC5 (FRET), PTPRC (Reconstituted Complex), CD48 (Reconstituted Complex), CD2BP2 (Two-hybrid), CD2BP2 (Reconstituted Complex), CD2 (Affinity Capture-Western), CD5 (Affinity Capture-Western)

ESM2 similar proteins: B7Z8K6, O02757, O35112, O46634, O46651, O70535, O95727, P01730, P01848, P01849, P01853, P01882, P03985, P03986, P06334, P06335, P06729, P0CF51, P0DSE1, P0DTU3, P10300, P16003, P16004, P16284, P20489, P23088, P23735, P31042, P31043, P42069, P42071, P42081, P42082, P42292, P42702, P46630, P51866, P79184, P79185, P97710

Diamond homologs: P06729, P08920, P08921, P37998, Q6SZ61, P0C9V8, A4FUY1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

541 predictions. Top by Δscore:

Variant	Effect	Δscore
1:116760399:TAGAG:T	acceptor_gain	1.0000
1:116760400:AGAGA:A	acceptor_gain	1.0000
1:116760401:GAGAG:G	acceptor_gain	1.0000
1:116754951:GGT:G	donor_loss	0.9900
1:116754952:G:T	donor_loss	0.9900
1:116754953:T:G	donor_loss	0.9900
1:116760110:GGT:G	donor_gain	0.9900
1:116760400:A:AG	acceptor_gain	0.9900
1:116760401:G:GG	acceptor_gain	0.9900
1:116760401:GA:G	acceptor_gain	0.9900
1:116760401:GAGA:G	acceptor_gain	0.9900
1:116764478:TTGCA:T	acceptor_loss	0.9900
1:116764479:TGCA:T	acceptor_loss	0.9900
1:116764480:GC:G	acceptor_loss	0.9900
1:116764481:C:CG	acceptor_loss	0.9900
1:116764482:A:AG	acceptor_gain	0.9900
1:116764483:G:GA	acceptor_loss	0.9900
1:116764483:G:GG	acceptor_gain	0.9900
1:116764483:GA:G	acceptor_gain	0.9900
1:116764605:TGGT:T	donor_loss	0.9900
1:116764606:GGTA:G	donor_loss	0.9900
1:116764607:G:GG	donor_gain	0.9900
1:116764607:GTA:G	donor_loss	0.9900
1:116764608:TAAG:T	donor_loss	0.9900
1:116768463:GAT:G	acceptor_gain	0.9900
1:116754493:A:G	donor_gain	0.9800
1:116760111:GT:G	donor_gain	0.9800
1:116760112:TT:T	donor_gain	0.9800
1:116764481:CAG:C	acceptor_gain	0.9800
1:116764482:AGA:A	acceptor_gain	0.9800

AlphaMissense

2322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:116754746:G:C	W59C	0.999
1:116754746:G:T	W59C	0.999
1:116754744:T:A	W59R	0.998
1:116754744:T:C	W59R	0.998
1:116760575:T:A	C186S	0.998
1:116760576:G:C	C186S	0.998
1:116760455:T:A	C146S	0.997
1:116760455:T:C	C146R	0.997
1:116760456:G:C	C146S	0.997
1:116754745:G:C	W59S	0.996
1:116754844:T:C	L92P	0.996
1:116760456:G:A	C146Y	0.996
1:116760575:T:C	C186R	0.996
1:116754697:T:C	L43S	0.995
1:116760457:T:G	C146W	0.995
1:116760450:T:C	L144P	0.994
1:116754882:T:G	Y105D	0.993
1:116754940:T:C	L124S	0.993
1:116760417:C:A	P133Q	0.993
1:116760577:C:G	C186W	0.993
1:116760589:C:A	N190K	0.993
1:116760589:C:G	N190K	0.993
1:116754850:T:C	I94T	0.991
1:116760416:C:T	P133S	0.991
1:116760492:T:C	L158P	0.991
1:116760547:G:C	W176C	0.991
1:116760547:G:T	W176C	0.991
1:116760417:C:G	P133R	0.990
1:116760576:G:A	C186Y	0.989
1:116754844:T:A	L92Q	0.988

dbSNP variants (sampled 300 via entrez): RS1000154635 (1:116758010 C>T), RS1000163147 (1:116768346 G>C), RS1000301312 (1:116756871 C>A), RS1000479252 (1:116767042 C>A), RS1000505836 (1:116758219 A>G), RS1000544056 (1:116766488 C>A), RS1000594968 (1:116766753 G>T), RS1000801519 (1:116761918 C>T), RS1001006537 (1:116762213 T>C), RS1001113619 (1:116756776 T>C), RS1001151814 (1:116761737 C>T), RS1001329888 (1:116762571 G>A), RS1001472655 (1:116756219 C>A,T), RS1001486574 (1:116762853 G>A), RS1001564404 (1:116756406 T>A,G)

Disease associations

OMIM: gene MIM:186990 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002318_147	Rheumatoid arthritis	8.000000e-10
GCST005568_52	Rheumatoid arthritis (ACPA-positive)	6.000000e-06
GCST006048_38	Rheumatoid arthritis (ACPA-positive)	9.000000e-08
GCST006959_122	Rheumatoid arthritis	9.000000e-07
GCST006959_31	Rheumatoid arthritis	5.000000e-08
GCST007932_59	Medication use (thyroid preparations)	4.000000e-08
GCST008158_138	Body mass index	7.000000e-06
GCST009597_248	Multiple sclerosis	5.000000e-06
GCST010273_1	Gout (normal type)	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009933	Thyroid preparation use measurement
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2040 (SINGLE PROTEIN), CHEMBL3885600 (PROTEIN-PROTEIN INTERACTION)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.9	nM	CHEMBL2153727
8.03	IC50	9.4	nM	CHEMBL2153727
7.96	IC50	11.1	nM	CHEMBL2153728
7.59	IC50	25.7	nM	CHEMBL2153728

PubChem BioAssay actives

4 with measured affinity, of 18 total; 2 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
2-[(3R,9S,12S,15S,18S,21S,24S,27S,30S,33S)-21-(4-aminobutyl)-15,24-bis[(2S)-butan-2-yl]-9,27-bis(carboxymethyl)-18-(hydroxymethyl)-12-[(4-hydroxyphenyl)methyl]-2,8,11,14,17,20,23,26,29,32-decaoxo-1,7,10,13,16,19,22,25,28,31-decazatricyclo[31.3.0.03,7]hexatriacontan-30-yl]acetic acid	689909: Inhibition of CD2-CD58 protein-protein interaction assessed as inhibition of cell adhesion between CD58 expressing human Caco2 cells and CD2 expressing human Jurkat cells by BCECF-AM fluorescent dye based fluorimetric assay	ic50	0.0069	uM
2-[(13S,16S,19S,22S,25S,28S)-19-(4-aminobutyl)-22-[(2S)-butan-2-yl]-13,16-bis(carboxymethyl)-25-[(4-hydroxyphenyl)methyl]-12,15,18,21,24,27,30-heptaoxo-2-oxa-11,14,17,20,23,26,29-heptazatetracyclo[31.4.0.03,8.04,37]heptatriaconta-1(33),3(8),4,6,34,36-hexaen-28-yl]acetic acid	689909: Inhibition of CD2-CD58 protein-protein interaction assessed as inhibition of cell adhesion between CD58 expressing human Caco2 cells and CD2 expressing human Jurkat cells by BCECF-AM fluorescent dye based fluorimetric assay	ic50	0.0111	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression, affects cotreatment, decreases expression	2
Arsenic	increases methylation, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dietary Carbohydrates	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Isotretinoin	increases expression	1
Tacrolimus	decreases reaction, increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023747	Binding	Inhibition of CD2-CD58 interaction assessed as inhibition of CD2 expressing human Jurkat T cell adhesion to CD58 expressing human Caco-2 cells at 90 uM after 45 mins by microplate fluorescence analysis	Design of beta-hairpin peptides for modulation of cell adhesion by beta-turn constraint. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D50	2C4 [Human fibrosarcoma]	Cancer cell line	Male
CVCL_1D51	2C4 gamma1A/JAK2	Cancer cell line	Male
CVCL_A8X0	BL2-5-8	Factor-dependent cell line
CVCL_C0D3	2C4 gamma1A	Cancer cell line	Male
CVCL_C0D4	2C4 gamma2A	Cancer cell line	Male
CVCL_C0D5	2C4 gamma2A/JAK2	Cancer cell line	Male
CVCL_E8IK	Jurkat-NFAT-Luc2-CD2-KO-1B4	Cancer cell line	Male
CVCL_E8IL	Jurkat-NFAT-Luc2-CD2-KO-2A2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer