Complement component 7 deficiency

Summary

Complement component 7 deficiency (MONDO:0012412) is a disease caused by C7 (GenCC Strong), inherited in an autosomal recessive pattern. Immunodeficiency due to a late component of complement deficiency is a primary immunodeficiency due to an anomaly in either complement components C5, C6, C7, C8 or C9 and is typically characterized by meningitis due to often recurrent meningococcal infections (Orphanet). This page aggregates 2 associated genes.

At a glance

• Causal gene: C7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 33
• Phenotypes (HPO): 3

Clinical features

Clinical description

Orphanet: Immunodeficiency due to a late component of complement deficiency is a primary immunodeficiency due to an anomaly in either complement components C5, C6, C7, C8 or C9 and is typically characterized by meningitis due to often recurrent meningococcal infections. The prognosis is generally favorable.

Mondo: Any classic complement early component deficiency in which the cause of the disease is a mutation in the C7 gene.

Inheritance: Autosomal recessive

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (curated from Orphanet + OMIM; top 3 shown, Orphanet frequencies first):

HPO ID	Term	Frequency
HP:0005381	Recurrent Neisseria meningitidis infection	—
HP:0005430	Recurrent Neisserial infections	—
HP:0033058	Decreased circulating complement C7 concentration	—

Identifiers

Disease identifiers

Field	Value
Canonical name	complement component 7 deficiency
Mondo ID	MONDO:0012412
MeSH	C566443
OMIM	610102
Orphanet	169150
DOID	DOID:0060300
UMLS	C1864694
MedGen	355270
GARD	0018290
Is cancer (heuristic)	no

Also known as: C7 classic complement early component deficiency · C7D · classic complement early component deficiency caused by mutation in C7 · complement component 7 deficiency

Data availability: 33 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › classic complement early component deficiency › complement component 7 deficiency Also classified under: immunodeficiency due to a late component of complement deficiency

Sibling subtypes (12): C1 inhibitor deficiency, complement component 2 deficiency, complement component 5 deficiency, complement component 6 deficiency, complement component 3 deficiency, complement component C1s deficiency, type II complement component 8 deficiency, type I complement component 8 deficiency, complement component 9 deficiency, complement component 4b deficiency, complement component 4a deficiency, … (+1 more under the parent term)

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

33 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 10 pathogenic, 5 pathogenic/likely pathogenic, 4 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12106	NM_000587.4(C7):c.63-1G>A	C7	Pathogenic	criteria provided, multiple submitters, no conflicts
12108	NM_000587.4(C7):c.1135G>C (p.Gly379Arg)	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225308	NM_000587.4(C7):c.281-1G>T	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280140	NM_000587.4(C7):c.1924_1925del (p.His643fs)	C7	Pathogenic	criteria provided, multiple submitters, no conflicts
432759	NM_000587.4(C7):c.405del (p.Asn136fs)	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871489	NM_000587.4(C7):c.633_643del (p.Ser212fs)	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723217	NM_000587.4(C7):c.614G>A (p.Trp205Ter)	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12109	NM_000587.4(C7):c.1314del (p.Lys438fs)	C7	Pathogenic	criteria provided, single submitter
4888333	GRCh38/hg38 5p13.1(chr5:40875740-41004828)x1	C7	Pathogenic	criteria provided, single submitter
12103	NM_000587.4(C7):c.2184T>A (p.Cys728Ter)	C7	Pathogenic	no assertion criteria provided
12104	NM_000587.4(C7):c.2140_2141del (p.Val714fs)	C7	Pathogenic	no assertion criteria provided
12107	C7, EX7-8DEL	C7	Pathogenic	no assertion criteria provided
12111	NM_000587.4(C7):c.1458T>A (p.Cys486Ter)	C7	Pathogenic	no assertion criteria provided
12112	C7, 11-BP DEL, NT631	C7	Pathogenic	no assertion criteria provided
635448	NM_000587.4(C7):c.317del (p.Asp106fs)	C7	Pathogenic	no assertion criteria provided
635449	NM_000587.4(C7):c.2350+1del	C7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
12105	NM_000587.4(C7):c.1561C>A (p.Arg521Ser)	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
636459	NM_000587.4(C7):c.2350+2T>C	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1014362	NM_000587.4(C7):c.1451C>T (p.Ala484Val)	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1460738	NM_000587.4(C7):c.391G>A (p.Asp131Asn)	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013250	NM_000587.4(C7):c.605A>G (p.Asn202Ser)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034275	NM_000587.4(C7):c.1411A>T (p.Thr471Ser)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1037979	NM_000587.4(C7):c.1852C>T (p.Arg618Trp)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1040255	NM_000587.4(C7):c.659G>A (p.Arg220Gln)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347654	NM_000587.4(C7):c.1205G>A (p.Arg402Gln)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1360430	NM_000587.4(C7):c.1136G>C (p.Gly379Ala)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1390238	NM_000587.4(C7):c.98A>G (p.Tyr33Cys)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1467907	NM_000587.4(C7):c.1909_1911dup (p.Met637dup)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1493533	NM_000587.4(C7):c.1244A>G (p.Gln415Arg)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1990394	NM_000587.4(C7):c.2125C>A (p.Gln709Lys)	C7	Uncertain significance	criteria provided, multiple submitters, no conflicts

Pathogenic / likely-pathogenic variants link to their full per-variant reference — ACMG evidence, calibrated predictors, gnomAD frequency — on Sugi Variant.

Genes & proteins

Molecular basis

The molecular function of this disease’s causal gene(s), from UniProt. Attributed to the gene/protein — reporting UniProt’s curation, not an assertion about this disease’s clinical phenotype.

C7 — Complement component C7 (P10643) · GenCC Strong · Belongs to the complement C6/C7/C8/C9 family. Function: Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis. Localization / cofactor: Secreted UniProt gene–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. Disease susceptibility is …

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

2 cohort genes:

Gene	Classification	Inheritance	Disease	Records
C7	Strong	Autosomal recessive	complement component 7 deficiency	3
CXCL10	Strong	Autosomal recessive	complement component 7 deficiency	3

Orphanet rare-disease linkage (cohort genes)

1 cohort genes:

Gene	Orphanet ID	Rare disease
C7	Orphanet:169150	Immunodeficiency due to a late component of complement deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes

2 cohort genes:

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CXCL10	HGNC:10637	ENSG00000169245	P02778	C-X-C motif chemokine 10	gencc,clinvar
C7	HGNC:1346	ENSG00000112936	P10643	Complement component C7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

2 cohort genes:

Symbol	Protein name	Function (lead sentence)
CXCL10	C-X-C motif chemokine 10	Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects.
C7	Complement component C7	Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort has 2 family-classified genes — counts only (too few for over-representation statistics).

Family	Genes
Other/Unknown	1
Complement	1

Per-gene assignment

2 cohort genes:

Symbol	Family	Druggable?	EC	InterPro (top 3)
CXCL10	Other/Unknown	no		Chemokine_CXC, Chemokine_IL8-like_dom, Chemokine_CXC_CS
C7	Complement	yes		Sushi_SCR_CCP_dom, TSP1_rpt, MAC_perforin

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

6 tissues:

Tissue	Cohort genes
decidua	1
male germ line stem cell (sensu Vertebrata) in testis	1
vermiform appendix	1
pericardium	1
right ovary	1
superficial temporal artery	1

Per-gene tissue summary

2 cohort genes:

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CXCL10	229	broad	marker	vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis, decidua
C7	238	broad	marker	right ovary, superficial temporal artery, pericardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CXCL10	3,919
C7	675

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures

2 cohort genes:

Symbol	UniProt	PDB entries
C7	P10643	8
CXCL10	P02778	6

Alliance gene associations

Curated gene–disease associations from the Alliance of Genome Resources (Disease Ontology) — distinct from the cohort above: implicated (causal/mechanistic) vs biomarker (a marker for the disease).

Implicated genes (1): C7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Cohort has 2 genes with Reactome annotation — too few for over-representation statistics, so the pathways below are membership (what the cohort genes participate in), not enrichment.

Pathways by enrichment

Cohort has 2 annotated genes — membership only (too few for over-representation statistics).

16 pathways:

Pathway	Genes	Sample cohort genes
Terminal pathway of complement	1	C7
Complement cascade	1	C7
Interleukin-10 signaling	1	CXCL10
Regulation of Complement cascade	1	C7
Immune System	2	CXCL10, C7
Chemokine receptors bind chemokines	1	CXCL10
Class A/1 (Rhodopsin-like receptors)	1	CXCL10
Peptide ligand-binding receptors	1	CXCL10
Signaling by Interleukins	1	CXCL10
GPCR ligand binding	1	CXCL10
GPCR downstream signalling	1	CXCL10
Cytokine Signaling in Immune system	1	CXCL10
Signaling by GPCR	1	CXCL10
G alpha (i) signalling events	1	CXCL10
Innate Immune System	1	C7
Signal Transduction	1	CXCL10

GO biological processes by enrichment

Cohort has 2 annotated genes — membership only (too few for over-representation statistics).

30 GO terms:

GO term	Genes	Sample cohort genes
regulation of T cell chemotaxis	1	CXCL10
regulation of endothelial tube morphogenesis	1	CXCL10
cellular response to interleukin-17	1	CXCL10
endothelial cell activation	1	CXCL10
complement activation, GZMK pathway	1	C7
T cell chemotaxis	1	CXCL10
complement activation, alternative pathway	1	C7
response to vitamin D	1	CXCL10
positive regulation of monocyte chemotaxis	1	CXCL10
response to auditory stimulus	1	CXCL10
positive regulation of T cell migration	1	CXCL10
complement activation	1	C7
response to gamma radiation	1	CXCL10
complement activation, classical pathway	1	C7
blood circulation	1	CXCL10
positive regulation of release of sequestered calcium ion into cytosol	1	CXCL10
positive regulation of immune response	1	C7
cellular response to heat	1	CXCL10
chemokine-mediated signaling pathway	1	CXCL10
neutrophil chemotaxis	1	CXCL10
killing of cells of another organism	1	C7
antiviral innate immune response	1	CXCL10
cellular response to virus	1	CXCL10
negative regulation of angiogenesis	1	CXCL10
transmembrane transport	1	C7
muscle organ development	1	CXCL10
chemotaxis	1	CXCL10
regulation of cell population proliferation	1	CXCL10
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	CXCL10
cellular response to lipopolysaccharide	1	CXCL10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CXCL10	0	0
C7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity

1 cohort genes by assay count:

Symbol	Assays	Type breakdown
CXCL10	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	C7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CXCL10

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

2 cohort genes:

Symbol	ChEMBL assays	Drugged partners (top 3)
CXCL10	2	—
C7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.