primary CD59 deficiency

Summary

primary CD59 deficiency (MONDO:0012858) is a disease caused by CD59 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CD59 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	primary CD59 deficiency
Mondo ID	MONDO:0012858
MeSH	C567355
OMIM	612300
Orphanet	169464
UMLS	C2676767
MedGen	393582
GARD	0017054
Is cancer (heuristic)	no

Also known as: HACD59 · hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy · primary CD59 deficiency

Data availability: 13 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › primary CD59 deficiency

Related subtypes (22): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, abetalipoproteinemia, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, hereditary cryohydrocytosis with reduced stomatin, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, elliptocytosis 1, glycogen storage disease due to aldolase A deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

13 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 4 pathogenic, 3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
100766	NM_000611.6(CD59):c.146del (p.Asp49fs)	CD59	Pathogenic	no assertion criteria provided
18052	NM_000611.6(CD59):c.123del (p.Val42fs)	CD59	Pathogenic	no assertion criteria provided
4848546	NM_000611.6(CD59):c.146A>T (p.Asp49Val)	CD59	Pathogenic	criteria provided, single submitter
64690	NM_000611.6(CD59):c.266G>A (p.Cys89Tyr)	CD59	Pathogenic	criteria provided, single submitter
1685256	NM_000611.6(CD59):c.83G>A (p.Cys28Tyr)	CD59	Likely pathogenic	criteria provided, single submitter
3599565	NM_000611.6(CD59):c.301del (p.Glu101fs)	CD59	Likely pathogenic	criteria provided, single submitter
3599566	NM_000611.6(CD59):c.190del (p.Cys64fs)	CD59	Likely pathogenic	criteria provided, single submitter
3599567	NM_000611.6(CD59):c.143_144del (p.Asp47_Phe48insTer)	CD59	Likely pathogenic	criteria provided, single submitter
3599568	NM_000611.6(CD59):c.2T>C (p.Met1Thr)	CD59	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3778882	NM_000611.6(CD59):c.282del (p.Leu93_Cys94insTer)	CD59	Likely pathogenic	criteria provided, single submitter
2585022	NM_000611.6(CD59):c.286_295del (p.Phe96fs)	CD59	Uncertain significance	criteria provided, single submitter
522723	NM_000611.6(CD59):c.190T>G (p.Cys64Gly)	CD59	Uncertain significance	criteria provided, single submitter
634643	NM_000611.6(CD59):c.85T>G (p.Tyr29Asp)	CD59	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD59	Strong	Autosomal recessive	primary CD59 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD59	Orphanet:169464	Primary CD59 deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD59	HGNC:1689	ENSG00000085063	P13987	CD59 glycoprotein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD59	CD59 glycoprotein	Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD59	Other/Unknown	no		LY6_UPA_recep-like, CD59_antigen_CS, Snake_toxin-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
right lung	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD59	295	ubiquitous	marker	stromal cell of endometrium, bronchial epithelial cell, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD59	2,167

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD59	P13987	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Complement cascade	1	634.4×	0.021	CD59
Cargo concentration in the ER	1	335.9×	0.021	CD59
Regulation of Complement cascade	1	233.1×	0.021	CD59
COPII-mediated vesicle transport	1	163.1×	0.021	CD59
ER to Golgi Anterograde Transport	1	132.8×	0.021	CD59
COPI-mediated anterograde transport	1	109.8×	0.021	CD59
Transport to the Golgi and subsequent modification	1	102.9×	0.021	CD59
Asparagine N-linked glycosylation	1	60.1×	0.031	CD59
Membrane Trafficking	1	37.1×	0.043	CD59
Vesicle-mediated transport	1	34.8×	0.043	CD59
Innate Immune System	1	25.5×	0.053	CD59
Neutrophil degranulation	1	23.1×	0.054	CD59
Post-translational protein modification	1	19.2×	0.060	CD59
Immune System	1	13.0×	0.081	CD59
Metabolism of proteins	1	12.4×	0.081	CD59

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of activation of membrane attack complex	1	5617.3×	5e-04	CD59
negative regulation of complement activation	1	3370.4×	5e-04	CD59
regulation of complement-dependent cytotoxicity	1	3370.4×	5e-04	CD59
negative regulation of complement-dependent cytotoxicity	1	3370.4×	5e-04	CD59
regulation of complement activation	1	2106.5×	7e-04	CD59
blood coagulation	1	173.7×	0.007	CD59
cell surface receptor signaling pathway	1	64.1×	0.016	CD59

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD59	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CD59

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CD59	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	CD59

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	CD59
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.