CD59

Chr 11AR

CD59 molecule (CD59 blood group)

Also known as: 16.3A5, 1F5, EJ16, EJ30, EL32, G344, HRF-20, HRF20

This gene encodes CD59, a cell surface glycoprotein that inhibits the complement membrane attack complex by binding to C8 and preventing incorporation of multiple C9 copies required for osmolytic pore formation. Mutations cause CD59 deficiency with autosomal recessive inheritance, resulting in hemolytic anemia and thrombosis that can lead to cerebral infarction, with or without immune-mediated polyneuropathy. The condition affects the hematologic system and can cause neurologic complications including stroke.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.001 OMIM phenotype
Clinical SummaryCD59
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
1.00LOEUF
pLI 0.606
Z-score 1.59
OE 0.00 (0.001.00)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint
-0.05Z-score
OE missense 1.02 (0.831.25)
67 obs / 66.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.001.00)
00.351.4
Missense OE1.02 (0.831.25)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 0 / 2.9Missense obs/exp: 67 / 66.0Syn Z: -0.29
DN
0.6259th %ile
GOF
0.5955th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

CD59 · 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 →