C9

complement C9, the group of Complement system activation components

Basic information

Region (hg38): 5:39284140-39371324

Links

ENSG00000113600 ∙ NCBI:735 ∙ OMIM:120940 ∙ HGNC:1358 ∙ Uniprot:P02748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complement component 9 deficiency (Moderate), mode of inheritance: Unknown
• complement component 9 deficiency (Strong), mode of inheritance: AR
• complement component 9 deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 9 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; Ophthalmologic	7430628; 2744767; 8747118; 9703418; 10083734; 12596049; 15943177; 21270745; 22123893; 22381107; 24036952; 32246154
In some individuals, there has been no evidence of "predicted" sequelae (eg, Neisseria infections)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C9 gene.

• not provided (23 variants)
• Complement component 9 deficiency (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C9 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				57	8	65
missense			132	11	7	150
nonsense	13	3				16
start loss						0
frameshift	10	6	3			19
inframe indel			4			4
splice donor/acceptor (+/-2bp)		3	1			4
splice region			4	8	1	13
non coding				28	5	33
Total	23	12	140	96	20

Highest pathogenic variant AF is 0.000565

Variants in C9

This is a list of pathogenic ClinVar variants found in the C9 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-39285201-AT-A		Complement component 9 deficiency • Complement component 9 deficiency;Age related macular degeneration 15	Uncertain significance (Aug 02, 2023)
5-39285209-T-C			Uncertain significance (Sep 10, 2022)
5-39285210-TG-T			Uncertain significance (Nov 25, 2022)
5-39285220-T-C			Likely benign (Sep 28, 2022)
5-39285236-A-G		C9-related disorder	Benign (Jan 19, 2024)
5-39285243-A-G			Likely benign (Oct 26, 2022)
5-39285247-A-G			Likely benign (Oct 15, 2023)
5-39288705-C-A			Likely benign (Jun 25, 2021)
5-39288706-A-G			Likely benign (Nov 10, 2023)
5-39288707-A-C			Likely benign (Jan 19, 2024)
5-39288709-T-C			Benign (Jan 21, 2024)
5-39288715-G-T			Likely benign (Mar 02, 2022)
5-39288718-C-T			Uncertain significance (Jan 28, 2021)
5-39288739-T-C			Likely benign (Apr 01, 2022)
5-39288741-T-C		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
5-39288742-A-G			Likely benign (Nov 22, 2023)
5-39288759-T-C		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
5-39288777-G-A			Uncertain significance (Jul 24, 2022)
5-39288781-G-A			Likely benign (Jan 16, 2024)
5-39288783-C-T		Age related macular degeneration 15;Complement component 9 deficiency	Conflicting classifications of pathogenicity (Dec 31, 2023)
5-39288785-C-T		Complement component 9 deficiency	Pathogenic (Feb 01, 1998)
5-39288787-CA-C			Uncertain significance (Feb 08, 2022)
5-39288832-T-A			Likely benign (Apr 07, 2023)
5-39288850-A-G			Likely benign (Aug 10, 2023)
5-39288855-A-G			Uncertain significance (Jun 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C9	protein_coding	protein_coding	ENST00000263408	11	140607

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.63e-24	0.0000911	125253	0	494	125747	0.00197

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.587	326	297	1.10	0.0000155	3670
Missense in Polyphen		114	103.84	1.0979		1256
Synonymous	-0.805	115	105	1.10	0.00000560	1019
Loss of Function	-0.696	34	29.9	1.14	0.00000174	359

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00196	0.00196
Ashkenazi Jewish	0.00258	0.00258
East Asian	0.0114	0.0114
Finnish	0.00495	0.00496
European (Non-Finnish)	0.000644	0.000642
Middle Eastern	0.0114	0.0114
South Asian	0.000719	0.000719
Other	0.00229	0.00228

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 (PubMed:9634479, PubMed:9212048, PubMed:26841934). C9 is the pore- forming subunit of the MAC (PubMed:4055801, PubMed:26841934). {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}.
• Disease: DISEASE: Complement component 9 deficiency (C9D) [MIM:613825]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may develop dermatomyositis. {ECO:0000269|PubMed:9634479}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 15 (ARMD15) [MIM:615591]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:24036952}. 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;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: 0.122

Intolerance Scores

• loftool: 0.372
• rvis_EVS: 1.45
• rvis_percentile_EVS: 95.12

Haploinsufficiency Scores

• pHI: 0.140
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.462

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: C9
• 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); 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)

Gene ontology

• Biological process: cell killing;complement activation, alternative pathway;complement activation, classical pathway;hemolysis by symbiont of host erythrocytes;regulation of complement activation;protein homooligomerization
• Cellular component: extracellular region;membrane attack complex;extracellular space;cytosol;plasma membrane;integral component of plasma membrane;other organism cell membrane;extracellular exosome;blood microparticle