C6

complement C6, the group of Sushi domain containing|Complement system activation components

Basic information

Region (hg38): 5:41142115-41261438

Links

ENSG00000039537 ∙ NCBI:729 ∙ OMIM:217050 ∙ HGNC:1339 ∙ Uniprot:P13671 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complement component 6 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 6 deficiency	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis (including related to specific immunization) and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	11344568; 11344569; 6835295; 8690922; 17257682; 17893986; 21270745; 22123893; 22288589; 22668955
Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C6 gene.

• not provided (360 variants)
• Inborn genetic diseases (40 variants)
• Complement component 6 deficiency (24 variants)
• not specified (7 variants)
• C6-related condition (3 variants)
• Immunodeficiency due to a late component of complement deficiency (1 variants)
• C6 deficiency, subtotal (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C6 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			2	65	8	75
missense			192	10	14	216
nonsense	9	4				13
start loss			1			1
frameshift	9	5				14
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		7				7
splice region		1	7	8	2	18
non coding			2	30	2	34
Total	18	16	198	106	24

Highest pathogenic variant AF is 0.00301

Variants in C6

This is a list of pathogenic ClinVar variants found in the C6 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-41142830-C-T			Benign (Jan 19, 2024)
5-41142837-C-T			Likely benign (Oct 24, 2023)
5-41142845-G-A			Uncertain significance (May 14, 2021)
5-41142851-G-A			Likely benign (Jan 12, 2024)
5-41142855-T-G			Uncertain significance (Jun 23, 2022)
5-41142888-C-T			Likely benign (Nov 29, 2022)
5-41142900-G-C			Uncertain significance (Apr 06, 2022)
5-41142931-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
5-41142934-T-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
5-41142940-C-T			Uncertain significance (Aug 16, 2022)
5-41142941-A-C			Uncertain significance (Aug 23, 2022)
5-41142950-G-C			Uncertain significance (Jun 16, 2021)
5-41142952-T-A			Uncertain significance (Oct 17, 2023)
5-41142958-C-A			Uncertain significance (Jul 06, 2022)
5-41142978-C-A			Uncertain significance (Feb 05, 2022)
5-41142980-A-G			Likely benign (Nov 08, 2022)
5-41142981-T-C			Likely benign (Nov 04, 2023)
5-41142987-G-A			Likely benign (Jun 15, 2022)
5-41142988-A-G			Uncertain significance (Jul 23, 2022)
5-41143001-T-C			Uncertain significance (Nov 15, 2021)
5-41143004-A-G			Uncertain significance (Jul 03, 2022)
5-41143007-C-T		Complement component 6 deficiency	Likely pathogenic (Mar 29, 2024)
5-41143011-A-G			Likely benign (May 22, 2023)
5-41143013-T-TGA			Benign (Jan 09, 2024)
5-41143025-A-T			Likely benign (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C6	protein_coding	protein_coding	ENST00000263413	17	119205

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.86e-22	0.141	124585	4	1153	125742	0.00461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.877	535	481	1.11	0.0000249	6128
Missense in Polyphen		165	167.1	0.98744		2112
Synonymous	-2.83	221	174	1.27	0.00000900	1696
Loss of Function	1.59	40	52.5	0.763	0.00000287	637

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0228	0.0226
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.00262	0.00261
Finnish	0.00157	0.00157
European (Non-Finnish)	0.00433	0.00432
Middle Eastern	0.00262	0.00261
South Asian	0.00389	0.00389
Other	0.00491	0.00490

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.
• Disease: DISEASE: Complement component 6 deficiency (C6D) [MIM:612446]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. {ECO:0000269|PubMed:15565285}. 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);Allograft Rejection;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement Activation;Complement and Coagulation Cascades;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: 0.105

Intolerance Scores

• loftool: 0.273
• rvis_EVS: 1.32
• rvis_percentile_EVS: 94.07

Haploinsufficiency Scores

• pHI: 0.0610
• hipred: N
• hipred_score: 0.410
• ghis: 0.378

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.547

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C6
• Phenotype: homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: in utero embryonic development;positive regulation of activation of membrane attack complex;complement activation;complement activation, classical pathway;cytolysis;regulation of complement activation;innate immune response;positive regulation of angiogenesis
• Cellular component: extracellular region;membrane attack complex;extracellular exosome
• Molecular function: protein binding