C5

complement C5, the group of C3 and PZP like, alpha-2-macroglobulin domain containing|Complement system activation components|Receptor ligands

Basic information

Region (hg38): 9:120932986-121075195

Links

ENSG00000106804 ∙ NCBI:727 ∙ OMIM:120900 ∙ HGNC:1331 ∙ Uniprot:P01031 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complement component 5 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Eculizumab, poor response to; Complement component 5 deficiency	AD/AR	Allergy/Immunology/Infectious; Pharmacogenomic	In Complement component 5 deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Heterozygous variants have been described as resulting in poor response to eculizumab	Craniofacial; Musculoskeletal; Neurologic	5411128; 4258194; 7730648; 21270745; 21635555; 22123893; 22668955; 23371790

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C5 gene.

• not provided (562 variants)
• Complement component 5 deficiency;Eculizumab, poor response to (54 variants)
• Eculizumab, poor response to;Complement component 5 deficiency (44 variants)
• Inborn genetic diseases (40 variants)
• Complement component 5 deficiency (11 variants)
• not specified (10 variants)
• C5-related condition (4 variants)
• Eculizumab, poor response to (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C5 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			3	121	9	133
missense			240	18	11	269
nonsense	4	1				5
start loss						0
frameshift	6	1				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)		6	1			7
splice region			28	29	2	59
non coding			8	79	11	98
Total	10	8	254	218	31

Highest pathogenic variant AF is 0.000394

Variants in C5

This is a list of pathogenic ClinVar variants found in the C5 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-120952739-T-C		Complement component 5 deficiency;Eculizumab, poor response to	Likely benign (Oct 05, 2023)
9-120952746-C-T			Uncertain significance (Sep 01, 2021)
9-120952753-A-G			Likely benign (Mar 13, 2023)
9-120952759-T-C		Complement component 5 deficiency;Eculizumab, poor response to • not specified	Uncertain significance (Aug 30, 2023)
9-120952765-C-T		Complement component 5 deficiency;Eculizumab, poor response to	Uncertain significance (Aug 25, 2022)
9-120952766-G-A			Likely benign (May 17, 2023)
9-120952774-C-T			Uncertain significance (Jul 12, 2022)
9-120952785-G-A			Uncertain significance (Aug 16, 2022)
9-120952802-C-T			Likely benign (Feb 11, 2023)
9-120952821-C-T		not specified	Uncertain significance (Oct 13, 2023)
9-120952838-C-G		Complement component 5 deficiency;Eculizumab, poor response to	Uncertain significance (Jul 06, 2021)
9-120952846-A-C		Complement component 5 deficiency;Eculizumab, poor response to	Uncertain significance (Aug 16, 2022)
9-120952853-T-C			Likely benign (Jan 29, 2024)
9-120952856-A-G			Likely benign (May 20, 2022)
9-120952858-G-A			Uncertain significance (Jan 07, 2022)
9-120952873-C-T			Uncertain significance (Jun 15, 2022)
9-120952880-C-T			Likely benign (Nov 21, 2022)
9-120953710-G-A			Likely benign (Aug 17, 2023)
9-120953711-A-C			Likely benign (Mar 03, 2023)
9-120953717-A-G			Likely benign (Oct 23, 2023)
9-120953723-G-T			Likely benign (Nov 17, 2023)
9-120953732-G-A		Eculizumab, poor response to;Complement component 5 deficiency	Likely benign (Jan 02, 2024)
9-120953758-GG-C		Complement component 5 deficiency	Pathogenic (Jan 01, 2005)
9-120953801-C-T			Likely benign (Oct 15, 2021)
9-120953805-G-T		not specified	Uncertain significance (Aug 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C5	protein_coding	protein_coding	ENST00000223642	41	97939

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.08e-24	1.00	125577	1	170	125748	0.000680

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	733	854	0.858	0.0000429	10961
Missense in Polyphen		145	229.43	0.632		2987
Synonymous	1.02	285	308	0.926	0.0000163	3114
Loss of Function	4.08	54	97.5	0.554	0.00000518	1216

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00353	0.00352
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00103	0.00103
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000379	0.000378
Middle Eastern	0.00103	0.00103
South Asian	0.000817	0.000784
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.
• Disease: DISEASE: Complement component 5 deficiency (C5D) [MIM:609536]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele. {ECO:0000269|PubMed:15995705}.
• Pathway: Prion diseases - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Pertussis - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Allograft Rejection;Spinal Cord Injury;Human Complement System;Oxidative Damage;Complement Activation;Signaling by GPCR;Signal Transduction;alternative complement pathway;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Activation of C3 and C5;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Regulation of Complement cascade;G alpha (i) signalling events;Terminal pathway of complement;Complement cascade;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.928
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.254
• hipred: N
• hipred_score: 0.420
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.771

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hc
• Phenotype: liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal 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); 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); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: activation of MAPK activity;in utero embryonic development;chemotaxis;inflammatory response;complement activation, alternative pathway;complement activation, classical pathway;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;positive regulation of vascular endothelial growth factor production;negative regulation of macrophage chemotaxis;negative regulation of endopeptidase activity;cytolysis;regulation of complement activation;positive regulation of angiogenesis;cell chemotaxis;positive regulation of chemokine secretion
• Cellular component: extracellular region;membrane attack complex;extracellular space;extracellular exosome
• Molecular function: endopeptidase inhibitor activity;signaling receptor binding;protein binding;chemokine activity