CD47
gene geneOn this page
Also known as IAPOA3
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
- GTEx eGene: eQTL in 29 tissues, sQTL in 10 (q < 0.05)
- Drug target: yes — 2 curated mechanism-of-action drugs
- Constraint (gnomAD): pLI 0.76 (intermediate), LOEUF 0.72 (unconstrained)
- MANE Select transcript:
NM_001777 - Interaction hub: 2,708 STRING partners (top 3% of genes corpus-wide)
- Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet
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: 34 — 29 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron
MANE Select: ENST00000361309
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 3: 1
ENST00000361309, ENST00000355354, ENST00000398258, ENST00000471694, ENST00000517766, ENST00000644850, ENST00000887585, ENST00000887586, ENST00000887587, ENST00000887588, ENST00000887589, ENST00000887590, ENST00000887591, ENST00000887592, ENST00000887593, ENST00000920144, ENST00000960414, ENST00000960415, ENST00000996835, ENST00000996836, ENST00000996837, ENST00000996838, ENST00000996839, ENST00001025723, ENST00001025724, ENST00001025725, ENST00001025726, ENST00001025727, ENST00001025728, ENST00001109443, ENST00001109444, ENST00001109445, ENST00001119566, ENST00001144942
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.
Highest expression (Bgee): gingival epithelium, esophagus squamous epithelium, gingiva, palpebral conjunctiva, squamous epithelium.
Genetic regulation across tissues (GTEx eQTL / sQTL)
CD47 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 39 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Cells EBV-transformed lymphocytes | eqtl | 5.0e-28 | -1.12 | 3:108124634:C:T |
| Esophagus Mucosa | sqtl | 3.6e-19 | -0.49 | 3:108041953:A:G |
| Artery Tibial | eqtl | 2.0e-16 | -0.32 | 3:108071544:A:G |
| Thyroid | sqtl | 6.7e-12 | -0.32 | 3:108041953:A:G |
| Whole Blood | eqtl | 4.3e-10 | +0.10 | 3:108100194:G:A |
| Artery Aorta | eqtl | 1.0e-09 | -0.24 | 3:107895076:T:C |
| Cells Cultured fibroblasts | eqtl | 1.6e-09 | -0.17 | 3:107959740:C:T |
| Adipose Subcutaneous | eqtl | 1.7e-08 | -0.16 | 3:108084656:A:C |
| Colon Transverse | eqtl | 6.0e-08 | -0.30 | 3:108084656:A:C |
| Esophagus Muscularis | eqtl | 1.1e-07 | -0.24 | 3:107957227:A:G |
| Esophagus Mucosa | eqtl | 4.0e-07 | +0.14 | 3:107988611:T:C |
| Lung | sqtl | 2.2e-06 | -0.25 | 3:108080618:A:T |
| Stomach | sqtl | 5.4e-06 | -0.22 | 3:108075605:T:C |
| Skin Not Sun Exposed Suprapubic | sqtl | 7.3e-06 | +0.27 | 3:108056320:C:T |
| Esophagus Gastroesophageal Junction | eqtl | 1.1e-05 | -0.22 | 3:108071544:A:G |
| Skin Sun Exposed Lower leg | sqtl | 1.4e-05 | -0.29 | 3:108041953:A:G |
| Adipose Visceral Omentum | eqtl | 1.6e-05 | -0.16 | 3:108044193:G:A |
| Spleen | eqtl | 4.6e-04 | -0.65 | 3:107977440:G:A |
| Stomach | eqtl | 1.2e-03 | -0.20 | 3:107957227:A:G |
| Nerve Tibial | eqtl | 1.3e-03 | -0.12 | 3:107935814:G:A |
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
showing 100 of 295 tissues 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 |
| substantia nigra pars compacta | UBERON:0001965 | 98.20 | gold quality |
| granulocyte | CL:0000094 | 98.14 | gold quality |
| parietal pleura | UBERON:0002400 | 98.12 | gold quality |
| lower lobe of lung | UBERON:0008949 | 98.08 | gold quality |
| cervix epithelium | UBERON:0004801 | 98.07 | gold quality |
| type B pancreatic cell | CL:0000169 | 98.06 | gold quality |
| tonsil | UBERON:0002372 | 98.06 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 98.05 | gold quality |
| fallopian tube | UBERON:0003889 | 98.05 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 98.03 | gold quality |
| choroid plexus epithelium | UBERON:0003911 | 98.02 | gold quality |
| synovial joint | UBERON:0002217 | 98.01 | gold quality |
| caecum | UBERON:0001153 | 97.99 | gold quality |
| mouth mucosa | UBERON:0003729 | 97.98 | gold quality |
| minor salivary gland | UBERON:0001830 | 97.96 | gold quality |
| subthalamic nucleus | UBERON:0001906 | 97.96 | gold quality |
| superior vestibular nucleus | UBERON:0007227 | 97.93 | gold quality |
| sperm | CL:0000019 | 97.90 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 97.89 | gold quality |
| right lung | UBERON:0002167 | 97.89 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 97.89 | gold quality |
| upper lobe of lung | UBERON:0008948 | 97.88 | gold quality |
| rectum | UBERON:0001052 | 97.87 | gold quality |
| bronchial epithelial cell | CL:0002328 | 97.85 | gold quality |
| gall bladder | UBERON:0002110 | 97.85 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 97.84 | gold quality |
| bone marrow cell | CL:0002092 | 97.82 | gold quality |
| lung | UBERON:0002048 | 97.80 | gold quality |
| esophagus mucosa | UBERON:0002469 | 97.80 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 97.79 | gold quality |
| bone marrow | UBERON:0002371 | 97.76 | gold quality |
| globus pallidus | UBERON:0001875 | 97.63 | gold quality |
| male germ cell | CL:0000015 | 97.62 | gold quality |
| medial globus pallidus | UBERON:0002477 | 97.61 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 97.59 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 97.58 | gold quality |
| entorhinal cortex | UBERON:0002728 | 97.49 | gold quality |
| vagina | UBERON:0000996 | 97.48 | gold quality |
| inferior vagus X ganglion | UBERON:0005363 | 97.42 | gold quality |
| medulla oblongata | UBERON:0001896 | 97.38 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 97.37 | gold quality |
| calcaneal tendon | UBERON:0003701 | 97.34 | gold quality |
| tendon | UBERON:0000043 | 97.32 | gold quality |
| skin of hip | UBERON:0001554 | 97.31 | gold quality |
| occipital lobe | UBERON:0002021 | 97.28 | gold quality |
| pylorus | UBERON:0001166 | 97.27 | gold quality |
| dorsal plus ventral thalamus | UBERON:0001897 | 97.27 | gold quality |
| prostate gland | UBERON:0002367 | 97.20 | gold quality |
| nasal cavity mucosa | UBERON:0001826 | 97.19 | gold quality |
| epithelium of bronchus | UBERON:0002031 | 97.18 | gold quality |
| olfactory bulb | UBERON:0002264 | 97.18 | gold quality |
| bronchus | UBERON:0002185 | 97.14 | gold quality |
| spleen | UBERON:0002106 | 97.12 | gold quality |
| endothelial cell | CL:0000115 | 97.11 | gold quality |
| primary visual cortex | UBERON:0002436 | 97.04 | gold quality |
| ventral tegmental area | UBERON:0002691 | 97.03 | gold quality |
| oral cavity | UBERON:0000167 | 97.00 | gold quality |
| leukocyte | CL:0000738 | 96.99 | gold quality |
| placenta | UBERON:0001987 | 96.94 | gold quality |
| dorsal root ganglion | UBERON:0000044 | 96.93 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 96.91 | gold quality |
| mononuclear cell | CL:0000842 | 96.85 | gold quality |
| monocyte | CL:0000576 | 96.84 | gold quality |
| thyroid gland | UBERON:0002046 | 96.84 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 96.78 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 96.77 | gold quality |
| seminal vesicle | UBERON:0000998 | 96.66 | gold quality |
| body of stomach | UBERON:0001161 | 96.65 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 96.64 | gold quality |
| caput epididymis | UBERON:0004358 | 96.60 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 78 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Retina | tissue | 264.3 | |
| Bone marrow | tissue | 219.0 | low |
| Tonsil | tissue | 151.2 | medium |
| Putamen | tissue | 146.5 | |
| Lung | tissue | 145.6 | not detected |
| Cerebral cortex | tissue | 143.7 | high |
| Occipital cortex | tissue | 143.7 | |
| Somatosensory cortex | tissue | 137.3 | |
| Motor cortex | tissue | 137.2 | |
| Retrosplenial and cingulate cortex | tissue | 133.9 | |
| Retrosplenial cortex | tissue | 133.0 | |
| Prefrontal cortex | tissue | 132.1 | |
| Basal ganglia | tissue | 131.5 | not detected |
| Lymph node | tissue | 128.6 | low |
| Cerebellum | tissue | 125.7 | high |
| Olfactory bulb | tissue | 121.2 | |
| Hippocampal formation | tissue | 117.2 | |
| Entorhinal cortex | tissue | 117.2 | |
| Insular cortex | tissue | 117.1 | |
| Ventral forebrain | tissue | 114.6 | |
| Prostate | tissue | 114.5 | high |
| Temporal cortex | tissue | 110.0 | |
| Appendix | tissue | 109.6 | low |
| Urinary bladder | tissue | 102.7 | high |
| Thalamus | tissue | 102.1 | |
| Midbrain | tissue | 102.0 | |
| Nucleus accumbens | tissue | 101.2 | |
| Septum | tissue | 99.9 | |
| Salivary gland | tissue | 98.9 | medium |
| Pons | tissue | 98.4 | |
| Stomach 1 | tissue | 98.1 | low |
| Postcentral gyrus | tissue | 94.9 | |
| Fallopian tube | tissue | 94.4 | high |
| Spleen | tissue | 94.2 | low |
| Rectum | tissue | 93.1 | medium |
| Superior colliculi | tissue | 90.5 | |
| Locus coeruleus | tissue | 89.4 | |
| Caudate putamen | tissue | 88.4 | |
| Esophagus | tissue | 88.2 | low |
| Epididymis | tissue | 87.0 | medium |
| Corpus callosum | tissue | 86.4 | |
| Thyroid gland | tissue | 85.3 | low |
| Breast | tissue | 83.4 | medium |
| Colon | tissue | 83.3 | low |
| Gallbladder | tissue | 81.3 | low |
| Amygdala | tissue | 78.3 | |
| Hypothalamus | tissue | 77.0 | |
| Placenta | tissue | 75.1 | medium |
| Small intestine | tissue | 74.5 | low |
| Thymus | tissue | 73.6 | |
| Hippocampus | tissue | 71.7 | not detected |
| Substantia nigra | tissue | 71.3 | |
| Duodenum | tissue | 70.1 | not detected |
| Spinal cord | tissue | 70.1 | |
| Medulla oblongata | tissue | 68.8 | |
| Liver | tissue | 66.6 | not detected |
| Periaqueductal gray | tissue | 66.4 | |
| Choroid plexus | tissue | 66.3 | |
| Frontal cortex | tissue | 64.5 | |
| Vagina | tissue | 63.6 | medium |
Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Corpus callosum, splenium (white matter) (157.3), Corpus callosum, genu (white matter) (153.5), Lateral funiculus (white matter) (143.2), Parieto-temporal junction (white matter) (142.3), Dorsal funiculus (white matter) (141.9).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): NRF1, SPI1
miRNA regulators (miRDB)
Targeting CD47 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 236 miRNAs:
| 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 |
Functional genomics
gnomAD constraint: pLI 0.759, LOEUF 0.725, missense Z 0.945 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD)
ENST00000361309 splits into 5 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| 3:108,047,291–108,059,503 | 131 / 135.3 | 0.97 | no |
| 3:108,059,504–108,080,047 | 65 / 119.9 | 0.54 | no |
| 3:108,080,048–108,080,146 | 47 / 36.2 | 1.30 | no |
| 3:108,080,147–108,080,279 | 25 / 52.7 | 0.47 | no |
| 3:108,080,280–108,090,908 | 38 / 42.7 | 0.89 | no |
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 |
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:96617) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 50 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| decreased hematocrit | 2 |
| increased susceptibility to bacterial infection | 2 |
| decreased leukocyte cell number | 1 |
| decreased neutrophil cell number | 1 |
| increased bone marrow cell number | 1 |
| abnormal hindlimb morphology | 1 |
| abnormal spleen morphology | 1 |
| enlarged spleen | 1 |
| decreased sensitivity to skin irradiation | 1 |
| abnormal skeleton physiology | 1 |
| hemolytic anemia | 1 |
| decreased tumor incidence | 1 |
| premature death | 1 |
| abnormal neutrophil physiology | 1 |
| impaired neutrophil phagocytosis | 1 |
| behavioral despair | 1 |
| increased heart rate | 1 |
| reticulocytosis | 1 |
| abnormal passive avoidance behavior | 1 |
| decreased hemoglobin content | 1 |
| abnormal excitatory postsynaptic potential | 1 |
| thrombocytopenia | 1 |
| abnormal physiological neovascularization | 1 |
| abnormal bone structure | 1 |
| abnormal muscle fiber morphology | 1 |
+25 more (showing top 25).
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Pongo abelii | Q5REL0 | 99.4% | Diamond |
| Sus scrofa | Q9GKE8 | 82.8% | Diamond |
| Bos taurus | Q9N0K1 | 82.8% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| IFT57 | protein-coding | 55081 |
| LINC01215 | ncRNA | 101929623 |
| LINC00636 | ncRNA | 285205 |
| LINC00635 | ncRNA | 151658 |
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 (52 total): strand 11, helix 11, 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 by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 2JJS | Structure of human CD47 in complex with human signal regulatory protein (SIRP) alpha | X-RAY DIFFRACTION | 1.85 |
| 2VSC | Structure of the immunoglobulin-superfamily ectodomain of human CD47 | X-RAY DIFFRACTION | 1.9 |
| 4CMM | Structure of human CD47 in complex with human Signal Regulatory Protein (SIRP) alpha v1 | X-RAY DIFFRACTION | 1.92 |
| 4KJY | Complex of high-affinity SIRP alpha variant FD6 with CD47 | X-RAY DIFFRACTION | 1.93 |
| 8RP8 | Structure of K2 Fab in complex with human CD47 ECD | X-RAY DIFFRACTION | 2 |
| 5TZU | Crystal structure of human CD47 ECD bound to Fab of B6H12.2 | X-RAY DIFFRACTION | 2.1 |
| 2JJT | Structure of human CD47 in complex with human signal regulatory protein (SIRP) alpha | X-RAY DIFFRACTION | 2.3 |
| 5TZ2 | Crystal structure of human CD47 ECD bound to Fab of C47B222 | X-RAY DIFFRACTION | 2.3 |
| 8ZCA | Crystal structure of human CD47 ECD bound to Fab of Hu1C8 | X-RAY DIFFRACTION | 2.5 |
| 7XJF | Crystal structure of 6MW3211 Fab in complex with CD47 | X-RAY DIFFRACTION | 2.6 |
| 7YGG | Crystal structure of human CD47 in complex with engineered SIRPa.D1(N80A) | X-RAY DIFFRACTION | 2.76 |
| 5IWL | CD47-diabody complex | X-RAY DIFFRACTION | 2.8 |
| 7WN8 | Crystal structure of antibody (BC31M5) binds to CD47 | X-RAY DIFFRACTION | 2.8 |
| 5TZT | Crystal structure of human CD47 ECD bound to Fab of C47B161 | X-RAY DIFFRACTION | 2.89 |
| 7MYZ | Structure of the full length 5-TM receptor CD47 bound to Fab B6H12 | X-RAY DIFFRACTION | 3.4 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q08722-F1 | 86.48 | 0.67 |
Antibody-complex structures (SAbDab)
12 antibodies co-crystallized with this protein: 5IWL, 5TZ2, 5TZT, 5TZU, 7MYZ, 7WN8, 7XJF, 8RP8, 8ZCA, MAGROLIMAB, SAFIMESTOMIG, ZERIPATAMIG
Human Protein Atlas
Protein class: CD markers, Transporters, Transporter channels and pores, Predicted membrane proteins, Predicted intracellular proteins
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): plasma membrane; vesicles
Antibody reliability (HPA): IH approved · IF supported
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (2)
| Type | Positions |
|---|---|
| Pyrrolidone carboxylic acid | 19 |
| Phosphoserine | 89 |
Disulfide bonds (2)
| Type | Positions |
|---|---|
| Disulfide bond | 33–263, 41–114 |
Glycosylation sites (6)
| Type | Positions |
|---|---|
| N-linked (glcnac…) asparagine | 23, 34, 50, 73, 111, 206 |
Function
Pathways and Gene Ontology
Reactome pathways
3 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
9 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-202733 | Cell surface interactions at the vascular wall | curated |
| R-HSA-216083 | Integrin cell surface interactions | curated |
| R-HSA-6798695 | Neutrophil degranulation | curated |
| R-HSA-1500931 | Cell-Cell communication | — |
| R-HSA-1474244 | Extracellular matrix organization | — |
| R-HSA-109582 | Hemostasis | — |
| R-HSA-168256 | Immune System | — |
| R-HSA-168249 | Innate Immune System | — |
| R-HSA-391160 | Signal regulatory protein family interactions | electronic |
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 (5): plasma membrane (GO:0005886), cell surface (GO:0009986), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821)
Reactome top-level categories
5 top-level categories:
| Category | Pathways |
|---|---|
| Hemostasis | 1 |
| Extracellular matrix organization | 1 |
| Cell-Cell communication | 1 |
| Innate Immune System | 1 |
| Immune System | 1 |
GO top-level categories
57 GO namespaces:
| Category | Terms |
|---|---|
| regulation of cytokine production | 4 |
| cell-cell adhesion | 2 |
| phagocytosis | 2 |
| regulation of phagocytosis | 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 |
| regulation of stress fiber assembly | 1 |
| Fc receptor mediated stimulatory signaling pathway | 1 |
| regulation of signal transduction | 1 |
| regulation of immune response | 1 |
| response to type II interferon | 1 |
| cellular response to cytokine stimulus | 1 |
| protein-containing complex binding | 1 |
| signaling receptor activity | 1 |
| heterotypic cell-cell adhesion | 1 |
| cell-cell adhesion mediator activity | 1 |
| cell adhesion mediator activity | 1 |
| binding | 1 |
| membrane | 1 |
| cell periphery | 1 |
| cellular anatomical structure | 1 |
| specific granule | 1 |
| extracellular vesicle | 1 |
| tertiary granule | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 15 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).
15 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| ATP export | BP | direct assay |
| cellular response to interleukin-12 | BP | mutant phenotype |
| positive regulation of T cell activation | BP | direct assay |
| positive regulation of cell population proliferation | BP | direct assay |
| positive regulation of cell-cell adhesion | BP | direct assay |
| regulation of interleukin-10 production | BP | mutant phenotype |
| regulation of interleukin-12 production | BP | mutant phenotype |
| regulation of interleukin-6 production | BP | mutant phenotype |
| regulation of tumor necrosis factor production | BP | mutant phenotype |
| regulation of type II interferon production | BP | mutant phenotype |
| cell surface | CC | direct assay |
| plasma membrane | CC | direct assay |
| cell-cell adhesion mediator activity | MF | physical interaction |
| fibrinogen binding | MF | direct assay |
| thrombospondin receptor activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 2,708 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| CD47 | SIRPA | P78324 | 971 |
| CD47 | SIRPG | Q9P1W8 | 881 |
| CD47 | RHAG | Q02094 | 873 |
| CD47 | THBS1 | P07996 | 823 |
| CD47 | H3BT10 | H3BT10 | 779 |
| CD47 | SIRPB1 | O00241 | 774 |
| CD47 | CD274 | Q9NZQ7 | 756 |
| CD47 | CALR | P27797 | 745 |
| CD47 | PRR13 | Q9NZ81 | 733 |
| CD47 | MYC | P01106 | 704 |
| CD47 | SCARB1 | Q8WTV0 | 690 |
| CD47 | GYPB | P06028 | 687 |
| CD47 | SCARB2 | Q14108 | 684 |
| CD47 | CD36 | P16671 | 684 |
| CD47 | CTLA4 | P16410 | 680 |
IntAct
Human interaction partners of CD47 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
7 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| SIRPA | direct interaction | 0.790 | 4 |
| SIRPG | physical association | 0.710 | 4 |
| SYNE4 | physical association | 0.560 | 3 |
| SIRPB1 | direct interaction | 0.440 | 1 |
| HLA-C | physical association | 0.400 | 1 |
| TMEM243 | physical association | 0.400 | 1 |
| ITGB1 | association | 0.350 | 1 |
BioGRID (93 interactions; top human partners by supporting records): LGALS9 (Affinity Capture-MS; 4 records), FAM134C (Affinity Capture-MS; 3 records), LGALS8 (Affinity Capture-MS; 3 records), SRC (Affinity Capture-Western; 3 records), TSPAN5 (Affinity Capture-MS; 3 records), BNIP3 (Two-hybrid; 2 records), BSCL2 (Affinity Capture-MS; 2 records), KLRG2 (Affinity Capture-MS; 2 records), LGALS9C (Affinity Capture-MS; 2 records), LILRB4 (Affinity Capture-MS; 2 records), S1PR1 (Affinity Capture-MS; 2 records), SLC1A5 (Affinity Capture-MS; 2 records), TM4SF18 (Affinity Capture-MS; 2 records), TRIM21 (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS)
SIGNOR signaling
2 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| CD47 | “form complex” | “Ankyrin complex” | binding |
| THBS2 | up-regulates | CD47 | binding |
Protein complexes (CORUM) (7)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
7 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| ★ ITGA2b-ITGB3-CD9-GP1b-CD47 complex | 5 | CD47, CD9, GP1BA, ITGA2B, ITGB3 |
| ★ ITGAV-ITGB3-CD47-FCER2 complex | 4 | CD47, FCER2, ITGAV, ITGB3 |
| ★ ITGA2b-ITGB3-CD47-SRC complex | 4 | CD47, ITGA2B, ITGB3, SRC |
| ★ ITGA2B-ITGB3-CD47-FAK complex | 4 | ITGA2B, ITGB3, PTK2, CD47 |
| ★ ITGB3-ITGAV-CD47 complex | 3 | CD47, ITGAV, ITGB3 |
| ★ ITGA4-ITGB1-CD47 complex | 3 | CD47, ITGA4, ITGB1 |
| ★ ITGA2-ITGB1-CD47 complex | 3 | CD47, ITGA2, ITGB1 |
Ligand–receptor pairs (CellPhoneDB) (3)
Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.
3 ligand–receptor pairs:
| Partner | This gene’s role | Signaling class |
|---|---|---|
| SIRPB1;TYROBP | ligand | |
| SIRPA | ligand | |
| SIRPG | ligand |
Disease & clinical
Genetic variants
Variant evidence for CD47: 63 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.
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 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 918):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 3:108047132 | donor_gain | 1.0000 | |
| 3:108059450–108059451 | donor_loss | 1.0000 | 5 |
| 3:108060854 | acceptor_gain | 1.0000 | |
| 3:108054299 | donor_gain | 0.9900 | |
| 3:108055512 | donor_gain | 0.9900 | |
| 3:108058335–108058336 | donor_loss | 0.9900 | 6 |
| 3:108059545–108059547 | acceptor_loss | 0.9900 | 7 |
| 3:108059555 | acceptor_loss | 0.9900 | |
| 3:108060743–108060744 | donor_loss | 0.9900 | 6 |
| 3:108060853–108060854 | acceptor_loss | 0.9900 | 5 |
AlphaMissense
850 missense substitutions predicted likely pathogenic (of 2,082 scored), across 232 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| F137 | 8 | 0.966 | 0.997 |
| F313 | 8 | 0.910 | 0.985 |
| N311 | 8 | 0.852 | 0.966 |
| F22 | 8 | 0.844 | 0.978 |
| F148 | 8 | 0.820 | 0.924 |
| C114 | 7 | 0.997 | 0.999 |
| C41 | 7 | 0.995 | 0.998 |
| W58 | 7 | 0.994 | 0.999 |
| C33 | 7 | 0.989 | 0.995 |
| C263 | 7 | 0.982 | 0.991 |
| W136 | 7 | 0.979 | 0.997 |
| W157 | 7 | 0.954 | 0.999 |
| F68 | 7 | 0.949 | 0.989 |
| E307 | 7 | 0.943 | 0.973 |
| E308 | 7 | 0.902 | 0.954 |
| E122 | 7 | 0.876 | 0.917 |
| N34 | 7 | 0.870 | 0.963 |
| E118 | 7 | 0.870 | 0.964 |
| F228 | 7 | 0.870 | 0.942 |
| F156 | 7 | 0.861 | 0.973 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
3 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 1.03e-05 |
| Lung Squamous Cell Carcinoma (TCGA) | unfavorable | 9.98e-05 |
| Thyroid Carcinoma (TCGA) | favorable | 0.00042 |
Disease associations
OMIM: gene MIM:601028 | disease phenotypes:
GWAS associations
7 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST006922_10 | Regular attendance at a religious group | 8e-12 |
| GCST010002_435 | Refractive error | 4e-10 |
| GCST011102_6 | Bipolar disorder | 2e-9 |
| GCST008103_182 | Bipolar disorder | 2e-8 |
| GCST012465_51 | Bipolar disorder | 4e-8 |
| GCST002783_603 | Body mass index | 2e-6 |
| GCST002783_224 | Body mass index | 5e-6 |
EFO canonical traits (from GWAS)
2 canonical traits:
| 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)
Drugs by curated mechanism of action (ChEMBL)
Drugs whose curated ChEMBL mechanism of action targets the CD47 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.
2 curated-mechanism drugs:
| Drug | Modality | Max phase |
|---|---|---|
| MAGROLIMAB | Antibody | 3 |
| EVORPACEPT | Protein | 2 |
PharmGKB: 1 entry (CPIC guideline: no)
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 |
Binding affinities (BindingDB)
20 measured of 20 human assays (20 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| CHEMBL4522427 | KD | 190 nM |
| CHEMBL3891508 | KD | 1200 nM |
| CHEMBL3946082 | KD | 1500 nM |
| CHEMBL3971661 | KD | 3040 nM |
| CHEMBL3900522 | KD | 6200 nM |
| CHEMBL4474790 | KD | 8600 nM |
| CHEMBL4462459 | KD | 9500 nM |
| CHEMBL3975422 | KD | 10000 nM |
| CHEMBL4570565 | KD | 13000 nM |
| CHEMBL4462869 | KD | 15000 nM |
| CHEMBL4585124 | KD | 17000 nM |
| CHEMBL3911226 | KD | 18000 nM |
| CHEMBL3974452 | KD | 19000 nM |
| CHEMBL4573126 | KD | 20000 nM |
| CHEMBL4449880 | KD | 21000 nM |
| CHEMBL3939184 | KD | 27000 nM |
| CHEMBL4471112 | KD | 36000 nM |
| CHEMBL4470419 | KD | 38000 nM |
| CHEMBL3899400 | KD | 42000 nM |
| CHEMBL4545895 | KD | 48000 nM |
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 31 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 | affects cotreatment, decreases expression, increases expression, affects expression, decreases methylation | 9 |
| Air Pollutants | increases abundance, increases expression, affects expression, decreases expression, affects cotreatment | 4 |
| Tetrachlorodibenzodioxin | decreases expression, decreases reaction, increases expression | 3 |
| Tobacco Smoke Pollution | decreases expression, affects expression | 3 |
| sodium arsenite | affects cotreatment, decreases expression, increases abundance | 2 |
| Arsenic | affects cotreatment, decreases expression, increases abundance | 2 |
| Vehicle Emissions | decreases expression, increases abundance | 2 |
| Benzo(a)pyrene | affects methylation, increases expression | 2 |
| Copper | increases expression, decreases expression, affects binding | 2 |
| Nickel | increases expression | 2 |
| Ozone | affects cotreatment, increases expression, increases abundance, affects expression | 2 |
| Smoke | decreases expression, increases abundance | 2 |
| Particulate Matter | decreases expression, increases abundance | 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 |
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)
Via MONDO — disease-level, not drug-specific.
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for CD47 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Targeted by drugs: Magrolimab