CD59

Chr 11AR

CD59 molecule (CD59 blood group)

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

NCBI Gene: 966ENSG00000085063UniProt: P13987

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathyMIM #612300
AR
1
Active trials
92
Pubs (1 yr)
32
P/LP submissions
10%
P/LP missense
1.00
LOEUF
DN
Mechanism· predicted
Clinical Summary— CD59
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 39 VUS of 146 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — CD59
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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

Highly tolerant — LoF variants common in population

Missense Constraint
-0.05Z-score
OE missense 1.02 (0.83–1.25)
67 obs / 66.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.00)
0≤0.351.4
Missense OE1.02 (0.83–1.25)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
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

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic7
VUS39
Likely Benign64
Benign2
Conflicting1
23
Pathogenic
7
Likely Pathogenic
39
VUS
64
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
20
0
23
Likely Pathogenic
3
2
2
0
7
VUS
2
31
6
0
39
Likely Benign
0
1
19
44
64
Benign
0
0
0
2
2
Conflicting
—1
Total7354746136

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Paroxysmal nocturnal haemoglobinuria.
Hill A et al.·Nat Rev Dis Primers
2017Review
The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.
Chen P et al.·Front Immunol
2021
The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.
Risitano AM et al.·Immunol Rev
2023Review
Congenital CD59 Deficiency.
Höchsmann B et al.·Hematol Oncol Clin North Am
2015Review
Complement and the prothrombotic state.
Schmidt CQ et al.·Blood
2022Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CD59 promotes pancreatic cancer progression via a tumor cell-intrinsic JAK2-STAT3 signaling axis.
Li Z et al.·Biochem Biophys Res Commun
2026
Glycated CD59: an emerging biomarker of diabetic nephropathy associated with microalbuminuria, tubular damage, and complement activation.
Chinta B et al.·J Diabetes Metab Disord
2026
Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Transfer CD59 to Astrocytes to Alleviate Complement-Dependent Cytotoxicity.
Shen Q et al.·Mol Neurobiol
2025
Genetic variants in the CD59 gene: An exploratory study of large genome databases.
Srivastava K et al.·Transfusion
2025Open Access
The Relationship of the Plasma Glycated CD59 Level with Microvascular Complications in Diabetic Patients and Its Evaluation as a Predictive Marker.
Yilmaz O et al.·J Clin Med
2025Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients