CD59

Chr 11AR

CD59 molecule (CD59 blood group)

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

NCBI Gene: 966 ENSG00000085063 UniProt: P13987 OMIM: 107271

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathyMIM #612300

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

148

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Mechanism· predicted

📖

GeneReview available — CD59

Authoritative clinical overview · Recommended first read

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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 OE?0.00 (0.00–1.00)

0≤0.351.4

Missense OE?1.02 (0.83–1.25)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 0 / 2.9Missense obs/exp: 67 / 66.0Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in CD59?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

213 rare PASS variants

Rare truncating (LoF)

1 in 640

37 rare PASS variants

Rare synonymous (reference)

1 in 200

66 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CD59; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 3,200
South Asian	~43k	1 in 200	1 in 3,700
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 15,000
European (Finnish)	~27k	1 in 1,100	1 in 3,800
Admixed American	~22k	1 in 200	≈ 1 in 22,000
African / African American	~21k	1 in 210	1 in 850
East Asian	~20k	1 in 280	≈ 1 in 16,000
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓