CD47

Summary

CD47 (CD47 molecule, HGNC:1682) is a protein-coding gene on chromosome 3q13.12, encoding Leukocyte surface antigen CD47 (Q08722). Adhesive protein that mediates cell-to-cell interactions.

This gene encodes a membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. The encoded protein is also a receptor for the C-terminal cell binding domain of thrombospondin, and it may play a role in membrane transport and signal transduction. This gene has broad tissue distribution, and is reduced in expression on Rh erythrocytes. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 961 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• MANE Select transcript: NM_001777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1682
Approved symbol	CD47
Name	CD47 molecule
Location	3q13.12
Locus type	gene with protein product
Status	Approved
Aliases	IAP, OA3
Ensembl gene	ENSG00000196776
Ensembl biotype	protein_coding
OMIM	601028
Entrez	961

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 retained_intron

ENST00000355354, ENST00000361309, ENST00000398258, ENST00000471694, ENST00000517766, ENST00000644850, ENST00000887585, ENST00000887586, ENST00000887587, ENST00000887588, ENST00000887589, ENST00000887590, ENST00000887591, ENST00000887592, ENST00000887593, ENST00000920144, ENST00000960414, ENST00000960415

RefSeq mRNA: 3 — MANE Select: NM_001777 NM_001382306, NM_001777, NM_198793

CCDS: CCDS43125, CCDS43126

Canonical transcript exons

ENST00000361309 — 11 exons

Exon	Start	End
ENSE00000774901	108051939	108051970
ENSE00000774903	108058337	108058429
ENSE00000774904	108059452	108059544
ENSE00000774905	108060745	108060852
ENSE00000774906	108071093	108071182
ENSE00000823360	108079991	108080344
ENSE00001369930	108049619	108049651
ENSE00001372086	108050578	108050602
ENSE00001840474	108043091	108047292
ENSE00001932120	108090863	108091031
ENSE00003526807	108057477	108057569

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.9116 / max 416.2548, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43654	50.1872	1812
43655	8.3170	1733
43653	0.7527	400
43649	0.5227	266
43652	0.1182	47
43648	0.0137	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	99.37	gold quality
esophagus squamous epithelium	UBERON:0006920	99.19	gold quality
gingiva	UBERON:0001828	99.17	gold quality
palpebral conjunctiva	UBERON:0001812	99.13	gold quality
squamous epithelium	UBERON:0006914	99.10	gold quality
germinal epithelium of ovary	UBERON:0001304	99.07	gold quality
visceral pleura	UBERON:0002401	98.98	gold quality
right uterine tube	UBERON:0001302	98.88	gold quality
epithelial cell of pancreas	CL:0000083	98.85	gold quality
epithelium of nasopharynx	UBERON:0001951	98.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.76	gold quality
tibia	UBERON:0000979	98.70	gold quality
oviduct epithelium	UBERON:0004804	98.70	gold quality
pancreatic ductal cell	CL:0002079	98.67	gold quality
epithelium of esophagus	UBERON:0001976	98.67	gold quality
postcentral gyrus	UBERON:0002581	98.64	gold quality
parietal lobe	UBERON:0001872	98.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.47	gold quality
cervix squamous epithelium	UBERON:0006922	98.46	gold quality
tendon of biceps brachii	UBERON:0008188	98.45	gold quality
pleura	UBERON:0000977	98.44	gold quality
pons	UBERON:0000988	98.43	gold quality
tongue squamous epithelium	UBERON:0006919	98.42	gold quality
lymph node	UBERON:0000029	98.38	gold quality
amniotic fluid	UBERON:0000173	98.33	gold quality
islet of Langerhans	UBERON:0000006	98.31	gold quality
vermiform appendix	UBERON:0001154	98.31	gold quality
endometrium epithelium	UBERON:0004811	98.31	gold quality
corpus callosum	UBERON:0002336	98.23	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.21	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	17.30
E-MTAB-9388	yes	11.75
E-MTAB-6678	yes	9.22
E-GEOD-130148	yes	6.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRF1, SPI1

miRNA regulators (miRDB)

236 targeting CD47, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 40)

• The Drosophila miR-959-962 Cluster Members Repress Toll Signaling to Regulate Antibacterial Defense during Bacterial Infection. (PMID:33477373)
• The interaction of CD47 with SHPS-1 may contribute to the recruitment of B lymphocytes via endothelial cells under steady state conditions. (PMID:11907074)
• Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior (PMID:11980922)
• regulates integrin function. Differential effects on alpha vbeta 3 and alpha 4beta1 integrin-mediated adhesion. (PMID:12218055)
• mechanism of antigen-induced caspase-independent cell death in normal and leukemic cells (PMID:12351399)
• An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis. (PMID:12370491)
• distribution of CD47, most restrained by cytoskeleton linkages plus a smaller fraction able to diffuse in the membrane, and colocalization with Rh protein complexes (PMID:12393442)
• Evidence protein 4.2 interacts with the Rh membrane complex member CD47 obtained from red cells of patients with hereditary spherocytosis associated with complete protein 4.2 deficiency (PMID:12393467)
• CD47 expressed on platelets significantly contributes to platelet adhesion on tumor necrosis factor-alpha (TNF-alpha)-stimulated vascular endothelial cells (PMID:12609828)
• Ligation of CD47 by any of its known ligands rapidly induces heterotrimeric Gi alpha-dependent but caspase-independent apoptosis in Jurkat T cells and, importantly, in activated primary T cells. (PMID:12646616)
• the extracellular Ig domain of IAP(CD47), when bound to thrombospondin, interacts with integrin alphaIIbbeta3 and can change alphaIIbbeta3 in a high affinity state without the requirement of intracellular signaling (PMID:12736272)
• Interaction of CD47 with thrombospondin-1 contributes to the perpetuation of inflammation in rheumatoid synovitis. (PMID:12902472)
• protein 4.2 strongly influences CD47 levels as well as the extent of membrane skeleton attachment in erythrocytes (PMID:14551146)
• IAP gene expression is regulated by alpha-Pal (PMID:14747477)
• CD47 recruits alpha(v)beta(3) and its associated signaling molecules to these domains (PMID:14966135)
• CD47 has a role in inducing alpha4beta1 integrin activation and adhesion in sickle reticulocytes (PMID:15292185)
• Review. The interaction between CD47 and SIRPalpha seems to be important to limit destruction of host cells in autoimmune diseases like autoimmune hemolytic anemia (AIHA), where macrophages destroy antibody or complement opsonized cells. (PMID:15359629)
• CD47 short interferint RNA inhibited cell proliferation in cultures of hepatoma cells. (PMID:15498560)
• Apoptosis inducing single-chain antibody fragments against cd47 antigens will be effective as a novel therapy for multiple myeloma. (PMID:15725479)
• SHPS-1 negatively regulates platelet function via CD47, especially alpha(IIb)beta(3)-mediated outside-in signaling (PMID:15842360)
• Novel CD47-dependent intercellular adhesion modulates cell movement. (PMID:15880429)
• CD47 associates with Fas upon its activation and augments Fas-mediated apoptosis. (PMID:15917238)
• SIRPalpha-CD47 interactions, which reportedly define self, exhibit cell type specificity and limited cross-species reactivity (PMID:16291597)
• RhD co-localizeS with CD47 but not calreticulin or glycophorin-A on human RBCs. (PMID:16581280)
• highlight major species differences in CD47-SIRPalpha interactions and CD47 integration, suggesting that signaling by CD47 in man may be qualitatively different from mouse. (PMID:16697668)
• CD47 stimulation by a thrombospondin-1 peptide induces naive or memory CD4+CD25- T cells to become suppressive. (PMID:16951312)
• analysis of species-specific CD47 interactions with signal regulatory protein alpha (PMID:17098740)
• Genetic induction of human CD47 on porcine cells could provide inhibitory signaling to SIRPalpha on human macrophages, providing a novel approach to preventing macrophage-mediated xenograft rejection. (PMID:17360380)
• In this review the authors provide mechanistic insight into the signaling pathways used by thrombospondin-1 and CD47 at the cellular and molecular level to prevent nitric oxide signaling through cyclic GMP, thereby exacerbating tissue ischemia. (PMID:17363705)
• Upregulation of CD47 in sporadic inclusion body myositis. (PMID:17572512)
• CD47/IAP is necessary for chondrocyte mechanotransduction. Through interactions with alpha5beta1 integrin and thrombospondin, CD47/IAP may modulate chondrocyte responses to mechanical signals. (PMID:18186923)
• On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47-SIRPalpha interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. (PMID:18332220)
• CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer. (PMID:18497546)
• A T cell-negative sensor that may serve to dampen unchecked proinflammatory T helper cell type 1 (Th1) responses, such as occur during contact hypersensitivity in transgenic mice. (PMID:18523271)
• CD47 is enriched at endothelial junctions, and its interaction with SIRPgamma is required for human T-cell transendothelial migration (PMID:18524990)
• These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. (PMID:18657508)
• TSP-1’s C-terminal domain opens to interact with the CD-47 receptor (PMID:18675774)
• In this review, the CD47/thrombospondin-1/signal-regulatory protein (SIRP)-alpha inhibitory axis is proposed as an important sensor to maintain homeostasis and regulate innate and adaptive immune responses. (PMID:18855618)
• Expression levels of CD47, CD35, CD55, and CD59 on red blood cells and signal-regulatory protein-alpha,beta on monocytes from patients with warm autoimmune hemolytic anemia. (PMID:18954403)
• Down-regulation of the IAP antagonistis XAF1, Smac/DIABLO and HtrA2, has been related to the onset and progression of various malignancies. (PMID:18979398)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd47	ENSMUSG00000055447
rattus_norvegicus	Cd47	ENSRNOG00000001964
rattus_norvegicus	LOC100909977	ENSRNOG00000042598

Protein

Protein identifiers

Leukocyte surface antigen CD47 — Q08722 (reviewed: Q08722)

Alternative names: Antigenic surface determinant protein OA3, Integrin-associated protein, Protein MER6

All UniProt accessions (5): A0A0A1TSG4, A0A2R8Y484, Q08722, H0YC40, H7BYS8

UniProt curated annotations — full annotation on UniProt →

Function. Adhesive protein that mediates cell-to-cell interactions. Acts as a receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation of heterotrimeric G proteins. Involved in signal transduction, cardiovascular homeostasis, inflammation, apoptosis, angiogenesis, cellular self-renewal, and immunoregulation. Plays a role in modulating pulmonary endothelin EDN1 signaling. Modulates nitrous oxide (NO) signaling, in response to THBS1, hence playing a role as a pressor agent, supporting blood pressure. Plays an important role in memory formation and synaptic plasticity in the hippocampus. Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. Positively modulates FAS-dependent apoptosis in T-cells, perhaps by enhancing FAS clustering. Plays a role in suppressing angiogenesis and may be involved in metabolic dysregulation during normal aging. In response to THBS1, negatively modulates wound healing. Inhibits stem cell self-renewal, in response to THBS1, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells.

Subunit / interactions. Monomer. Interacts with THBS1 (via the C-terminal domain). Interacts with SIRPA. Interacts with FAS/CD95; interaction may be enhanced by functional activation. Interacts with SIRPG, UBQLN1 and UBQLN2. May interact with fibrinogen. Interacts with Aedes aegypti neutrophil-stimulating factor 1; the interaction results in inhibition of phagocytosis activity of macrophages.

Subcellular location. Cell membrane.

Tissue specificity. Very broadly distributed on normal adult tissues, as well as ovarian tumors, being especially abundant in some epithelia and the brain. Macrophages.

Induction. Induced in pulmonary artery and lung parenchyma following injury or stress. Expression in arteries increases in normal aging.

Isoforms (4)

UniProt ID	Names	Canonical?
Q08722-1	OA3-323	yes
Q08722-2	OA3-293
Q08722-3	OA3-305
Q08722-4	OA3-312

RefSeq proteins (3): NP_001369235, NP_001768, NP_942088 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006704	CD47	Family
IPR007110	Ig-like_dom	Domain
IPR013147	CD47-like_TM	Domain
IPR013270	CD47_Vset	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037805	IgV_CD47	Domain

Pfam: PF04549, PF08204

UniProt features (51 total): strand 11, helix 10, topological domain 6, glycosylation site 6, transmembrane region 5, splice variant 4, modified residue 2, disulfide bond 2, turn 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2JJS	X-RAY DIFFRACTION	1.85
2VSC	X-RAY DIFFRACTION	1.9
4CMM	X-RAY DIFFRACTION	1.92
4KJY	X-RAY DIFFRACTION	1.93
8RP8	X-RAY DIFFRACTION	2
5TZU	X-RAY DIFFRACTION	2.1
2JJT	X-RAY DIFFRACTION	2.3
5TZ2	X-RAY DIFFRACTION	2.3
8ZCA	X-RAY DIFFRACTION	2.5
7XJF	X-RAY DIFFRACTION	2.6
7YGG	X-RAY DIFFRACTION	2.76
5IWL	X-RAY DIFFRACTION	2.8
7WN8	X-RAY DIFFRACTION	2.8
5TZT	X-RAY DIFFRACTION	2.89
7MYZ	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08722-F1	86.48	0.67

Antibody-complex structures (SAbDab): 9 — 5IWL, 5TZ2, 5TZT, 5TZU, 7MYZ, 7WN8, 7XJF, 8RP8, 8ZCA

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): 19, 89

Disulfide bonds (2): 33–263, 41–114

Glycosylation sites (6): 23, 34, 50, 73, 111, 206

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-391160	Signal regulatory protein family interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-1474244	Extracellular matrix organization
R-HSA-1500931	Cell-Cell communication
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 504 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, MORF_MBD4, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, TGCGCANK_UNKNOWN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MORF_RAB5A, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6

GO Biological Process (28): angiogenesis (GO:0001525), apoptotic process (GO:0006915), inflammatory response (GO:0006954), integrin-mediated signaling pathway (GO:0007229), positive regulation of cell population proliferation (GO:0008284), cell migration (GO:0016477), positive regulation of cell-cell adhesion (GO:0022409), regulation of type II interferon production (GO:0032649), regulation of interleukin-10 production (GO:0032653), regulation of interleukin-12 production (GO:0032655), regulation of interleukin-6 production (GO:0032675), regulation of tumor necrosis factor production (GO:0032680), regulation of nitric oxide biosynthetic process (GO:0045428), positive regulation of inflammatory response (GO:0050729), negative regulation of phagocytosis (GO:0050765), positive regulation of phagocytosis (GO:0050766), positive regulation of T cell activation (GO:0050870), positive regulation of stress fiber assembly (GO:0051496), regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368), cellular response to type II interferon (GO:0071346), cellular response to interleukin-1 (GO:0071347), cellular response to interleukin-12 (GO:0071349), ATP export (GO:1904669), positive regulation of monocyte extravasation (GO:2000439), positive regulation of immune system process (GO:0002684), cell adhesion (GO:0007155), heterotypic cell-cell adhesion (GO:0034113), cell-cell adhesion (GO:0098609)

GO Molecular Function (5): fibrinogen binding (GO:0070051), thrombospondin receptor activity (GO:0070053), protein binding involved in heterotypic cell-cell adhesion (GO:0086080), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Hemostasis	1
Extracellular matrix organization	1
Cell-Cell communication	1
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cytokine production	4
cell-cell adhesion	2
phagocytosis	2
regulation of phagocytosis	2
cellular anatomical structure	2
secretory granule membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell motility	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
type II interferon production	1
interleukin-10 production	1
interleukin-12 production	1
interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor superfamily cytokine production	1
nitric oxide biosynthetic process	1
regulation of biosynthetic process	1
regulation of nitric oxide metabolic process	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
negative regulation of endocytosis	1
positive regulation of endocytosis	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1

Protein interactions and networks

STRING

2604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD47	SIRPA	P78324	999
CD47	SIRPG	Q9P1W8	998
CD47	THBS1	P07996	997
CD47	SCARB1	Q8WTV0	994
CD47	SCARB2	Q14108	994
CD47	CD36	P16671	994
CD47	GYPB	P06028	993
CD47	RHAG	Q02094	993
CD47	CD200R1	Q8TD46	990
CD47	PTPRC	P08575	975
CD47	H3BT10	H3BT10	944
CD47	UBQLN1	Q9UMX0	944
CD47	GYPA	P02724	940
CD47	KDR	P35968	939
CD47	RHCE	P18577	932

IntAct

63 interactions, top by confidence:

A	B	Type	Score
SIRPA	CD47	psi-mi:“MI:0407”(direct interaction)	0.790
CD47	SIRPA	psi-mi:“MI:0915”(physical association)	0.790
CD47	SIRPA	psi-mi:“MI:0407”(direct interaction)	0.790
SIRPG	CD47	psi-mi:“MI:0915”(physical association)	0.710
SIRPG	CD47	psi-mi:“MI:0407”(direct interaction)	0.710
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
CD47	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	CD47	psi-mi:“MI:0915”(physical association)	0.560
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD47	SIRPA	psi-mi:“MI:0407”(direct interaction)	0.440
SIRPB1	CD47	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM243	CD47	psi-mi:“MI:0915”(physical association)	0.400
CD47	HLA-C	psi-mi:“MI:0915”(physical association)	0.400
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATP2B4	FLOT1	psi-mi:“MI:0914”(association)	0.350
AQP1	FLOT1	psi-mi:“MI:0914”(association)	0.350
CD47	ITGB1	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
sseJ	sseL	psi-mi:“MI:0914”(association)	0.350
	NPC1	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC7A14	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): SYNE4 (Two-hybrid), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), UBQLN1 (Affinity Capture-Western), GNB3 (Affinity Capture-Western), GNAQ (Affinity Capture-Western), GNAS (Affinity Capture-Western), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS), CD47 (Affinity Capture-MS)

ESM2 similar proteins: A1YIY0, O54901, O88775, P04218, P08920, P09693, P0DST5, P0DST6, P0DTU3, P12371, P20352, P20489, P21061, P21995, P24763, P31041, P31042, P42082, P42533, P58550, P97829, Q04790, Q08722, Q13296, Q13478, Q28074, Q28589, Q2YHT7, Q3T113, Q501W4, Q59I63, Q5REL0, Q61098, Q61735, Q62611, Q640U3, Q6GMZ9, Q6PCB8, Q764M8, Q7TSP5

Diamond homologs: P97829, Q08722, Q5REL0, Q61735, Q9GKE8, Q9N0K1, A0A7H0DND7, P0DST5, P0DST6, P24763

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CD47	“form complex”	“Ankyrin complex”	binding
THBS2	up-regulates	CD47	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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
Neutrophil degranulation	10	5.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1701 predictions. Top by Δscore:

Variant	Effect	Δscore
3:108047132:A:C	donor_gain	1.0000
3:108047172:A:AC	donor_gain	1.0000
3:108047173:C:CC	donor_gain	1.0000
3:108047173:CTTTT:C	donor_gain	1.0000
3:108057568:CG:C	acceptor_gain	1.0000
3:108059447:CTCA:C	donor_loss	1.0000
3:108059448:TCAC:T	donor_loss	1.0000
3:108059449:CACCT:C	donor_loss	1.0000
3:108059450:ACCTG:A	donor_loss	1.0000
3:108059451:C:G	donor_loss	1.0000
3:108060850:GTG:G	acceptor_gain	1.0000
3:108060854:T:C	acceptor_gain	1.0000
3:108060854:T:TC	acceptor_gain	1.0000
3:108071178:TGAAA:T	acceptor_gain	1.0000
3:108071183:C:CC	acceptor_gain	1.0000
3:108090862:CCG:C	donor_gain	1.0000
3:108055512:T:A	donor_gain	0.9900
3:108057475:AC:A	donor_gain	0.9900
3:108057476:CC:C	donor_gain	0.9900
3:108057566:CACG:C	acceptor_gain	0.9900
3:108057570:C:CC	acceptor_gain	0.9900
3:108058330:CTCTT:C	donor_loss	0.9900
3:108058331:TCTTA:T	donor_loss	0.9900
3:108058332:CTTA:C	donor_loss	0.9900
3:108058333:TTA:T	donor_loss	0.9900
3:108058334:TAC:T	donor_loss	0.9900
3:108058335:ACCCG:A	donor_loss	0.9900
3:108058336:C:A	donor_loss	0.9900
3:108058427:TCG:T	acceptor_gain	0.9900
3:108058428:CG:C	acceptor_gain	0.9900

AlphaMissense

2082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:108071114:A:G	W157R	0.999
3:108071114:A:T	W157R	0.999
3:108080050:C:G	C114S	0.999
3:108080051:A:G	C114R	0.999
3:108080051:A:T	C114S	0.999
3:108080217:C:A	W58C	0.999
3:108080217:C:G	W58C	0.999
3:108080219:A:G	W58R	0.999
3:108080219:A:T	W58R	0.999
3:108058358:C:G	G255R	0.998
3:108058358:C:T	G255R	0.998
3:108060766:C:G	G193R	0.998
3:108060766:C:T	G193R	0.998
3:108080049:A:C	C114W	0.998
3:108080050:C:T	C114Y	0.998
3:108080098:A:G	L98S	0.998
3:108080218:C:G	W58S	0.998
3:108080268:G:C	C41W	0.998
3:108080270:A:G	C41R	0.998
3:108071172:A:C	F137L	0.997
3:108071172:A:T	F137L	0.997
3:108071174:A:G	F137L	0.997
3:108071177:A:G	W136R	0.997
3:108071177:A:T	W136R	0.997
3:108080269:C:G	C41S	0.997
3:108080269:C:T	C41Y	0.997
3:108080270:A:T	C41S	0.997
3:108071175:C:A	W136C	0.996
3:108071175:C:G	W136C	0.996
3:108080057:A:C	Y112D	0.996

dbSNP variants (sampled 300 via entrez): RS1000061088 (3:108081189 T>C), RS1000096947 (3:108059955 C>G,T), RS1000114154 (3:108084124 C>T), RS1000211451 (3:108074076 T>G), RS1000411792 (3:108048381 T>TG), RS1000416656 (3:108080944 A>G), RS1000451169 (3:108088243 T>C,G), RS1000540504 (3:108087765 T>C), RS1000652265 (3:108048294 C>A), RS1000656386 (3:108088190 T>C), RS1000660041 (3:108069516 T>G), RS1000695173 (3:108066926 T>C), RS1000705912 (3:108048385 T>C,G), RS1000787516 (3:108080603 G>A), RS1000842038 (3:108083205 T>C)

Disease associations

OMIM: gene MIM:601028 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002783_174	Body mass index	5.000000e-06
GCST002783_228	Body mass index	2.000000e-06
GCST006922_10	Regular attendance at a religious group	8.000000e-12
GCST008103_22	Bipolar disorder	2.000000e-08
GCST010002_435	Refractive error	4.000000e-10
GCST011102_6	Bipolar disorder	2.000000e-09
GCST012465_51	Bipolar disorder	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009592	social interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3714583 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
magrolimab	Binding	11.1	pKd
ligufalimab	Binding	9.49	pEC50
evorpacept	Binding	9.0	pKd
ontorpacept	Binding	7.85	pEC50

ChEMBL bioactivities

10 potent at pChembl≥5 of 25 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.72	Kd	190	nM	CHEMBL4522427
6.11	Kd	771	nM	CHEMBL3946082
5.92	Kd	1200	nM	CHEMBL3891508
5.82	Kd	1500	nM	CHEMBL3946082
5.64	Kd	2280	nM	CHEMBL3974452
5.52	Kd	3040	nM	CHEMBL3971661
5.21	Kd	6200	nM	CHEMBL3900522
5.07	Kd	8600	nM	CHEMBL4474790
5.02	Kd	9500	nM	CHEMBL4462459
5.00	Kd	1e+04	nM	CHEMBL3975422

PubChem BioAssay actives

10 with measured affinity, of 3806 total; 9 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
(2R)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-6-amino-2-[5-[4-[[bis[[1-[5-[[(2R)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(1R)-5-amino-1-carboxypentyl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-methylamino]-1-oxohexan-2-yl]amino]-5-oxopentyl]triazol-4-yl]methyl]amino]methyl]triazol-1-yl]pentanoylamino]hexanoyl]-methylamino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-(1H-indol-3-yl)propyl]amino]hexanoyl]amino]hexanoic acid	1615551: Binding affinity to CD47 in biotinylated human MEC1 cell membranes by biolayer interferometry	kd	0.1900	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanamide	1316205: Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	kd	0.7710	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide	1316205: Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	kd	1.2000	uM
(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]hexanoic acid	1316205: Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	kd	2.2800	uM
(2R)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]hexanoic acid	1316205: Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	kd	3.0400	uM
(2R)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2,6-diaminohexanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]hexanoic acid	1316206: Binding affinity to CD47 receptor in human biotinylated MEC1 cell membranes by biolayer interferometry	kd	6.2000	uM
(2R)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2,6-diaminohexanoyl]-methylamino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]hexanoic acid	1615551: Binding affinity to CD47 in biotinylated human MEC1 cell membranes by biolayer interferometry	kd	8.6000	uM
(2R)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2,6-diaminohexanoyl]-methylamino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]hexanoic acid	1615551: Binding affinity to CD47 in biotinylated human MEC1 cell membranes by biolayer interferometry	kd	9.5000	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoic acid	1316205: Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	kd	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression, increases expression, affects expression	9
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression, decreases expression	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Copper	affects binding, increases expression, decreases expression	2
Nickel	increases expression	2
Ozone	increases expression, increases abundance, affects expression, affects cotreatment	2
bisphenol F	increases expression	1
beauvericin	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
senecionine	increases expression	1
terbufos	decreases methylation	1
trichostatin A	increases expression	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
enniatins	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3855090	Binding	Binding affinity to CD47 receptor in human NT.115-labeled MEC1 cell membranes after 5 mins by MST assay	Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies. — J Med Chem

Cellosaurus cell lines

16 cell lines: 10 cancer cell line, 4 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TU	Abcam HEK293T CD47 KO	Transformed cell line	Female
CVCL_D7M6	Ubigene A-549 CD47 KO	Cancer cell line	Male
CVCL_D8IP	Ubigene HCT 116 CD47 KO	Cancer cell line	Male
CVCL_D9ZN	Ubigene HeLa CD47 KO	Cancer cell line	Female
CVCL_E1G9	Abcam MCF-7 CD47 KO	Cancer cell line	Female
CVCL_E6BK	MC38-hPD-L1-hCD47-LZ	Cancer cell line	Female
CVCL_E6PN	Genomeditech CHO-K1 H_CD47	Spontaneously immortalized cell line	Female
CVCL_E6PP	Genomeditech CHO-K1 H_CD47 aAPC	Spontaneously immortalized cell line	Female
CVCL_E6WD	Genomeditech MC-38 H_CD47	Cancer cell line	Female
CVCL_E8IT	Jurkat-NFAT-Luc2-CD47-KO-1B3	Cancer cell line	Male

Clinical trials (associated diseases)

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