C8A

complement C8 alpha chain, the group of Complement system activation components

Basic information

Region (hg38): 1:56854768-56918223

Links

ENSG00000157131 ∙ NCBI:731 ∙ OMIM:120950 ∙ HGNC:1352 ∙ Uniprot:P07357 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• type I complement component 8 deficiency (Strong), mode of inheritance: AR
• type I complement component 8 deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 8 deficiency, type I	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	6822660; 6433145; 9759902; 21270745; 22123893

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C8A gene.

• not_provided (353 variants)
• not_specified (78 variants)
• C8A-related_disorder (14 variants)
• Type_I_complement_component_8_deficiency (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C8A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000562.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	102	4	108
missense			173	12	8	193
nonsense	13	3	1			17
start loss						0
frameshift	5					5
splice donor/acceptor (+/-2bp)		6				6
Total	18	9	176	114	12

Highest pathogenic variant AF is 0.000031469215

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C8A	protein_coding	protein_coding	ENST00000361249	11	63416

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.55e-16	0.0552	125676	0	72	125748	0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.07	372	318	1.17	0.0000179	3841
Missense in Polyphen		106	103.81	1.0211		1270
Synonymous	-1.10	135	120	1.13	0.00000676	1073
Loss of Function	0.749	26	30.5	0.854	0.00000166	362

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000839	0.000838
Ashkenazi Jewish	0.00	0.00
East Asian	0.000439	0.000435
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000212	0.000211
Middle Eastern	0.000439	0.000435
South Asian	0.000457	0.000457
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C8A inserts into the target membrane, but does not form pores by itself. {ECO:0000269|PubMed:17872444, ECO:0000269|PubMed:7440581}.
• Disease: DISEASE: Complement component 8 deficiency, 1 (C8D1) [MIM:613790]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Prion diseases - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Allograft Rejection;Human Complement System;Complement Activation;alternative complement pathway;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Regulation of Complement cascade;Terminal pathway of complement;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.275
• rvis_EVS: 1.58
• rvis_percentile_EVS: 95.79

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.219

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.764

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: C8a

Gene ontology

• Biological process: immune response;complement activation;complement activation, alternative pathway;complement activation, classical pathway;cytolysis;regulation of complement activation
• Cellular component: extracellular region;membrane attack complex;extracellular space;membrane;extracellular exosome;blood microparticle
• Molecular function: complement binding;protein-containing complex binding