CD47

Chr 3

CD47 molecule

Also known as: IAP, MER6, OA3

NCBI Gene: 961 ENSG00000196776 UniProt: Q08722 OMIM: 601028

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.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.37

Clinical Summary— CD47

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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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.37LOEUF

pLI 0.919

Z-score 3.36

OE 0.12 (0.05–0.37)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.43Z-score

OE missense 0.68 (0.58–0.80)

108 obs / 158.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.37)

0≤0.351.4

Missense OE?0.68 (0.58–0.80)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 16.9Missense obs/exp: 108 / 158.7Syn Z: -0.18

This gene — mechanism propensity

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.