CD59

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

Basic information

Region (hg38): 11:33703010-33736479

Previous symbols: [ "MIC11", "MIN1", "MSK21", "MIN2", "MIN3", "MIRL", "MACIF", "HRF20" ]

Links

ENSG00000085063 ∙ NCBI:966 ∙ OMIM:107271 ∙ HGNC:1689 ∙ Uniprot:P13987 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary CD59 deficiency (Moderate), mode of inheritance: AR
• primary CD59 deficiency (Supportive), mode of inheritance: AR
• primary CD59 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy	AR	Allergy/Immunology/Infectious; Hematologic	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	Allergy/Immunology/Infectious; Hematologic; Neurologic	1691667; 1699124; 1382994; 21707954; 23149847

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD59 gene.

• Primary CD59 deficiency (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD59 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				35	5	40
missense	1	1	26			28
nonsense						0
start loss			1			1
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	4		5
non coding				13		13
Total	1	2	29	48	5

Variants in CD59

This is a list of pathogenic ClinVar variants found in the CD59 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-33710129-G-T			Likely benign (Dec 25, 2023)
11-33710131-G-A			Uncertain significance (Aug 23, 2022)
11-33710147-T-G			Likely benign (Jun 09, 2023)
11-33710152-C-A			Uncertain significance (Jul 14, 2022)
11-33710153-C-T			Likely benign (Aug 23, 2022)
11-33710171-CAGA-C			Uncertain significance (Sep 21, 2023)
11-33710180-T-C			Likely benign (Feb 18, 2023)
11-33710185-T-G			Uncertain significance (Mar 12, 2022)
11-33710194-A-G			Likely benign (Jul 29, 2023)
11-33710195-G-C			Likely benign (Mar 08, 2023)
11-33710200-T-G		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)
11-33710211-T-G			Uncertain significance (May 27, 2022)
11-33710211-TC-T		Primary CD59 deficiency	Likely pathogenic (Feb 13, 2024)
11-33710212-C-T			Uncertain significance (Nov 22, 2021)
11-33710214-A-C			Uncertain significance (Aug 21, 2022)
11-33710215-G-A			Uncertain significance (Nov 22, 2021)
11-33710217-TGTTCGTTAAA-T		Primary CD59 deficiency	Uncertain significance (-)
11-33710221-C-G			Uncertain significance (Apr 06, 2022)
11-33710222-G-A			Likely benign (Jan 28, 2024)
11-33710225-A-C			Uncertain significance (Nov 28, 2023)
11-33710225-A-G			Likely benign (Dec 13, 2023)
11-33710227-AG-A		not specified	Uncertain significance (Apr 09, 2024)
11-33710239-C-T		Inborn genetic diseases	Uncertain significance (Jul 15, 2024)
11-33710246-G-A			Likely benign (Jun 24, 2023)
11-33710247-C-T		Primary CD59 deficiency	Pathogenic (May 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD59	protein_coding	protein_coding	ENST00000395850	3	38185

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.606	0.361	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0451	67	66.0	1.02	0.00000385	829
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Human Complement System;Neutrophil degranulation;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Cargo concentration in the ER;EGFR1;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Regulation of Complement cascade;COPI-mediated anterograde transport;Complement cascade;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.436
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.0203
• hipred: N
• hipred_score: 0.123
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd59b
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; renal/urinary system phenotype

Gene ontology

• 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;neutrophil degranulation;COPII vesicle coating
• Cellular component: Golgi membrane;extracellular space;endoplasmic reticulum membrane;plasma membrane;focal adhesion;cell surface;ER to Golgi transport vesicle membrane;membrane;transport vesicle;anchored component of external side of plasma membrane;vesicle;endoplasmic reticulum-Golgi intermediate compartment membrane;specific granule membrane;extracellular exosome;tertiary granule membrane
• Molecular function: complement binding;protein binding