CD59

protein-coding

CD59 molecule (CD59 blood group), the group of Complement system regulators and receptors|Blood group antigens|CD molecules|LY6/PLAUR domain containing

Gene summary

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]

Previous symbols:

MIC11
MIN1
MSK21
MIN2
MIN3
MIRL
MACIF
HRF20

MANE transcript

NM_000611.6

Inheritance

ClinVar variants

P:11U:37B:48

Top phenotype

Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr11:33,703,010-33,736,479

External References & Databases

Ensembl (ENSG00000085063)

Transcript & Mutation Effects

hg38 • Region Span ~33.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary CD59 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012858

Submitter: Ambry Genetics

primary CD59 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012858

Submitter: Labcorp Genetics (formerly Invitae)

primary CD59 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012858

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathyAR

Manifestation: Allergy/Immunology/Infectious; Hematologic; Neurologic

Intervention: Allergy/Immunology/Infectious; Hematologic

Rationale: Surveillance to allow early diagnosis and treatment of manifestations including hemolytic anemia, as well as thrombotic risk, may be beneficial; Immunosuppressive treatment has been reported as resulting in clinical improvement

Refs: 1691667; 1699124; 1382994; 21707954; 23149847

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD59 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 96

Primary CD59 deficiencyTotal: 13

not specifiedTotal: 13

Inborn genetic diseasesTotal: 9

CD59-related disorderTotal: 5

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000611.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				44 clinvar	2 clinvar	46
missense	2 clinvar	1 clinvar	32 clinvar	2 clinvar		37
nonsense			1 clinvar			1
start loss		1 clinvar	1 clinvar			2
frameshift	2 clinvar	5 clinvar	2 clinvar			9
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	7	37	46	2	96

Highest pathogenic variant AF is 0.000003420389

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 75 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000611.6	RefSeq	NP_000602.1	3	MANE Select
ENST00000642928.2	Ensembl	ENSP00000494884.1	3	MANE Select
NM_001127223.1	RefSeq	NP_001120695.1	3	Standard
NM_001127225.2	RefSeq	NP_001120697.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Hematopoietic cell lineage - Homo sapiens (human)
Human Complement System
Neutrophil degranulation
Vesicle-mediated transport

Biological Process

negative regulation of activation of membrane attack complex
endoplasmic reticulum to Golgi vesicle-mediated transport
cell surface receptor signaling pathway
blood coagulation
regulation of complement activation

Molecular Function

complement binding
protein binding

Cellular Component

Golgi membrane
extracellular space
endoplasmic reticulum membrane
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395850
Coding exons: 3
Length: 38185
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0451	67	66.0	1.02	0.00000385	829
Missense (PolyPhen)		16	19.525	0.81944		259
Synonymous	-0.293	32	30.0	1.07	0.00000211	244
Loss of Function	1.59	0	2.93	0.00	1.23e-7	36

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase.;
Disease: DISEASE: Hemolytic anemia, CD59-mediated, with or without polyneuropathy (HACD59) [MIM:612300]: An autosomal recessive disorder characterized by infantile onset of chronic hemolysis and a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifested as hypotonia, limb muscle weakness, and hyporeflexia. {ECO:0000269|PubMed:1382994, ECO:0000269|PubMed:23149847}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.206

Intolerance Scores

LoFtool: 0.436
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low