CD47

Chr 3

CD47 molecule

Also known as: IAP, MER6, OA3

The protein CD47 is a membrane adhesion protein that serves as a receptor for thrombospondin and modulates integrin signaling, playing roles in cell-to-cell interactions, cardiovascular homeostasis, inflammation, and immunoregulation. Mutations cause autosomal recessive defects affecting multiple systems including hematologic, cardiovascular, and neurologic manifestations. This gene is highly constrained against loss-of-function variants, indicating that complete loss of CD47 function is likely to cause significant clinical effects.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.37
Clinical SummaryCD47
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.919
Z-score 3.36
OE 0.12 (0.050.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.43Z-score
OE missense 0.68 (0.580.80)
108 obs / 158.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.050.37)
00.351.4
Missense OE0.68 (0.580.80)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 2 / 16.9Missense obs/exp: 108 / 158.7Syn Z: -0.18
DN
0.6356th %ile
GOF
0.6540th %ile
LOF
0.3744th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CD47 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Emerging phagocytosis checkpoints in cancer immunotherapy.
Liu Y et al.·Signal Transduct Target Ther
2023Review
Targeting CD47 for cancer immunotherapy.
Jiang Z et al.·J Hematol Oncol
2021Review
Tolerating CD47.
Isenberg JS et al.·Clin Transl Med
2024Review
CD47/SIRPα axis: bridging innate and adaptive immunity.
van Duijn A et al.·J Immunother Cancer
2022Review
Top 5 results · since 2015Search PubMed ↗