C7

protein-coding

complement C7, the group of Complement system activation components|Sushi domain containing

Gene summary

This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

MANE transcript

NM_000587.4

Inheritance

ClinVar variants

P:69U:300B:180

Top phenotype

Complement component 7 deficiency

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr5:40,909,492-41,020,216

External References & Databases

Ensembl (ENSG00000112936)

Transcript & Mutation Effects

hg38 • Region Span ~110.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complement component 7 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012412

Submitter: Labcorp Genetics (formerly Invitae)

complement component 7 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012412

Submitter: Ambry Genetics

complement component 7 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012412

Submitter: Illumina

Clinical Genomic Database (CGD)

Complement component 7 deficiencyAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial

Refs: 3685247; 2792129; 8892662; 8871666; 17407100; 15328683; 21270745; 22123893; 20591074; 22206826

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C7 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 574

Inborn genetic diseasesTotal: 144

not specifiedTotal: 52

Complement component 7 deficiencyTotal: 31

C7-related disorderTotal: 21

C7-related disordersTotal: 13

Primary immunodeficiency or monogenic inflammatory bowel diseaseTotal: 1

C7 and C6 deficiency, combined subtotalTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000587.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	159 clinvar	3 clinvar	166
missense		2 clinvar	290 clinvar	17 clinvar	1 clinvar	310
nonsense	16 clinvar	6 clinvar	1 clinvar			23
start loss						0
frameshift	18 clinvar	4 clinvar				22
splice donor/acceptor (+/-2bp)	2 clinvar	21 clinvar	5 clinvar			28
Total	36	33	300	176	4	549

Highest pathogenic variant AF is 0.0031138458

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000587.4	RefSeq	NP_000578.2	18	MANE Select
ENST00000313164.10	Ensembl	ENSP00000322061.9	18	MANE Select
ENST00000489457.2	Ensembl	ENSP00000512585.1	6	Standard
ENST00000489457.3	Ensembl	ENSP00000512585.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prion diseases - Homo sapiens (human)
Complement and coagulation cascades - Homo sapiens (human)
Systemic lupus erythematosus - Homo sapiens (human)
Allograft Rejection
Human Complement System

Biological Process

cellular sodium ion homeostasis
complement activation
complement activation, alternative pathway
complement activation, classical pathway
cytolysis

Cellular Component

extracellular region
membrane attack complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313164
Coding exons: 18
Length: 73688
Individuals with no LoFs: 124364
Homozygous LoFs: 0
Heterozygous LoFs: 273
Defined: 124637
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.644	470	432	1.09	0.0000223	5460
Missense (PolyPhen)		138	136.08	1.0141		1717
Synonymous	-1.98	193	161	1.20	0.00000906	1550
Loss of Function	2.07	29	43.8	0.663	0.00000202	593

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0036	0.0036	notable
Latino/Admixed American	0.0013	0.0013	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0021	0.0021	notable
Finnish	0.00048	0.00046	rare
European (Non-Finnish)	0.0011	0.0010	notable
South Asian	0.00013	0.00013	rare
Other	0.00088	0.00083	rare

dbNSFP Gene Annotations

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. C7 serves as a membrane anchor.;
Disease: DISEASE: Complement component 7 deficiency (C7D) [MIM:610102]: 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:8871666, ECO:0000269|PubMed:9218625, ECO:0000269|PubMed:9856499}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.598
RVIS EVS: -0.21
RVIS percentile EVS: 37.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.694

Gene Damage Prediction

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