Complement component 7 deficiency

Summary

Complement component 7 deficiency (MONDO:0012412) is a disease caused by C7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: C7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	complement component 7 deficiency
Mondo ID	MONDO:0012412
MeSH	C566443
OMIM	610102
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: 32 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

Related subtypes (12): C1 inhibitor deficiency, complement component C1r/C1s 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

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

32 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 9 pathogenic, 5 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign/likely benign, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
12106	NM_000587.4(C7):c.63-1G>A	C7	Pathogenic	criteria provided, multiple submitters, no conflicts
12107	C7, EX7-8DEL	C7	Pathogenic	no assertion criteria provided
12109	NM_000587.4(C7):c.1314del (p.Lys438fs)	C7	Pathogenic	criteria provided, single submitter
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
1723217	NM_000587.4(C7):c.614G>A (p.Trp205Ter)	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
635448	NM_000587.4(C7):c.317del (p.Asp106fs)	C7	Pathogenic	no assertion criteria provided
871489	NM_000587.4(C7):c.633_643del (p.Ser212fs)	C7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635449	NM_000587.4(C7):c.2350+1del	C7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1014362	NM_000587.4(C7):c.1451C>T (p.Ala484Val)	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12105	NM_000587.4(C7):c.1561C>A (p.Arg521Ser)	C7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12108	NM_000587.4(C7):c.1135G>C (p.Gly379Arg)	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
636459	NM_000587.4(C7):c.2350+2T>C	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
1166124	NM_000587.4(C7):c.1341G>A (p.Glu447=)	C7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

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.

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)

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 (full)

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.

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 families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	1	134.0×	0.015
Other/Unknown	1	0.9×	0.805

Per-gene assignment

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

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 (top 30)

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	3,798
C7	763

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C7	P10643	8
CXCL10	P02778	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Terminal pathway of complement	1	713.8×	0.007	C7
Interleukin-10 signaling	1	116.5×	0.013	CXCL10
Regulation of Complement cascade	1	116.5×	0.013	C7
Chemokine receptors bind chemokines	1	93.6×	0.013	CXCL10
G alpha (i) signalling events	1	19.5×	0.051	CXCL10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of T cell chemotaxis	1	4213.0×	0.008	CXCL10
negative regulation of myoblast fusion	1	2106.5×	0.008	CXCL10
regulation of endothelial tube morphogenesis	1	1685.2×	0.008	CXCL10
cellular response to interleukin-17	1	1203.7×	0.008	CXCL10
endothelial cell activation	1	842.6×	0.009	CXCL10
complement activation, GZMK pathway	1	648.1×	0.009	C7
T cell chemotaxis	1	561.7×	0.009	CXCL10
complement activation, alternative pathway	1	495.6×	0.009	C7
response to vitamin D	1	401.2×	0.009	CXCL10
positive regulation of monocyte chemotaxis	1	401.2×	0.009	CXCL10
response to auditory stimulus	1	366.4×	0.009	CXCL10
positive regulation of T cell migration	1	366.4×	0.009	CXCL10
complement activation	1	312.1×	0.009	C7
negative regulation of myoblast differentiation	1	312.1×	0.009	CXCL10
response to gamma radiation	1	290.6×	0.009	CXCL10
complement activation, classical pathway	1	271.8×	0.009	C7
blood circulation	1	255.3×	0.009	CXCL10
positive regulation of release of sequestered calcium ion into cytosol	1	247.8×	0.009	CXCL10
positive regulation of immune response	1	240.7×	0.009	C7
cellular response to heat	1	172.0×	0.012	CXCL10
chemokine-mediated signaling pathway	1	162.0×	0.012	CXCL10
neutrophil chemotaxis	1	142.8×	0.013	CXCL10
killing of cells of another organism	1	135.9×	0.013	C7
antiviral innate immune response	1	113.9×	0.015	CXCL10
cellular response to virus	1	100.3×	0.016	CXCL10
negative regulation of angiogenesis	1	84.3×	0.017	CXCL10
transmembrane transport	1	84.3×	0.017	C7
muscle organ development	1	83.4×	0.017	CXCL10
chemotaxis	1	68.0×	0.020	CXCL10
regulation of cell population proliferation	1	57.7×	0.023	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 (full, sorted 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).

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.