Complement component 5 deficiency

Summary

Complement component 5 deficiency (MONDO:0012295) is a disease caused by C5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: C5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 116

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	complement component 5 deficiency
Mondo ID	MONDO:0012295
OMIM	609536
DOID	DOID:8158
NCIT	C9469
UMLS	C0343047
MedGen	91003
GARD	0002191
Is cancer (heuristic)	no

Also known as: C5 complement deficiency · C5 deficiency · C5D · complement component 5 deficiency · complement deficiency caused by mutation in C5 · dysfunction of the fifth component of complement (C5)

Data availability: 116 ClinVar variants · 1 GenCC gene-disease record.

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 5 deficiency

Related subtypes (12): C1 inhibitor deficiency, complement component C1r/C1s deficiency, complement component 2 deficiency, complement component 7 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

116 retrieved; paginated sample, class counts are floors:

57 uncertain significance, 26 likely benign, 15 benign/likely benign, 8 conflicting classifications of pathogenicity, 5 pathogenic, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1451489	NM_001735.3(C5):c.1407G>A (p.Trp469Ter)	C5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17050	NM_001735.3(C5):c.55C>T (p.Gln19Ter)	C5	Pathogenic	criteria provided, multiple submitters, no conflicts
17051	NM_001735.3(C5):c.4426C>T (p.Arg1476Ter)	C5	Pathogenic	criteria provided, multiple submitters, no conflicts
17052	NM_001735.3(C5):c.4872_4873delinsG (p.Leu1625fs)	C5	Pathogenic	no assertion criteria provided
17053	NM_001735.3(C5):c.1115A>G (p.Lys372Arg)	C5	Pathogenic	no assertion criteria provided
4532110	NM_001735.3(C5):c.3610C>T (p.Gln1204Ter)	C5	Pathogenic	criteria provided, single submitter
1488270	NM_001735.3(C5):c.2257+1G>A	C5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1500220	NM_001735.3(C5):c.4679-2A>G	C5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779470	NM_001735.3(C5):c.65+1G>A	C5	Likely pathogenic	criteria provided, single submitter
517604	NM_001735.3(C5):c.4336del (p.Val1446fs)	C5	Likely pathogenic	criteria provided, single submitter
1000584	NM_001735.3(C5):c.2033C>T (p.Thr678Met)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1385681	NM_001735.3(C5):c.3732G>A (p.Thr1244=)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1402097	NM_001735.3(C5):c.1704C>T (p.Gly568=)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1407585	NM_001735.3(C5):c.1717-5T>C	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1443344	NM_001735.3(C5):c.3277G>A (p.Val1093Ile)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1482689	NM_001735.3(C5):c.975T>A (p.Ile325=)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1579708	NM_001735.3(C5):c.64A>G (p.Thr22Ala)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
982690	NM_001735.3(C5):c.989T>C (p.Ile330Thr)	C5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1006498	NM_001735.3(C5):c.4204A>G (p.Ile1402Val)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1009377	NM_001735.3(C5):c.754G>A (p.Ala252Thr)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1018051	NM_001735.3(C5):c.691A>G (p.Ile231Val)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033860	NM_001735.3(C5):c.65C>T (p.Thr22Ile)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033861	NM_001735.3(C5):c.95G>A (p.Arg32His)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1049928	NM_001735.3(C5):c.4143C>A (p.Ile1381=)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1059514	NM_001735.3(C5):c.3068A>G (p.His1023Arg)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
127072	NM_001735.3(C5):c.2653C>T (p.Arg885Cys)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1284901	NM_001735.3(C5):c.2420C>T (p.Thr807Ile)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342383	NM_001735.3(C5):c.4654G>A (p.Ala1552Thr)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1345729	NM_001735.3(C5):c.2059+3A>G	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1346229	NM_001735.3(C5):c.1816G>A (p.Asp606Asn)	C5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
C5	Strong	Autosomal recessive	complement component 5 deficiency

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C5	Orphanet:169150	Immunodeficiency due to a late component of complement deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C5	HGNC:1331	ENSG00000106804	P01031	Complement C5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C5	Complement C5	Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune sy…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C5	Complement	yes	3.4.21.43	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
oocyte	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C5	231	ubiquitous	marker	right lobe of liver, liver, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C5	1,337

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C5	P01031	42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1427.5×	0.002	C5
Activation of C3 and C5	1	1268.9×	0.002	C5
Regulation of Complement cascade	1	233.1×	0.007	C5
Peptide ligand-binding receptors	1	74.2×	0.017	C5
G alpha (i) signalling events	1	39.0×	0.026	C5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of macrophage chemotaxis	1	2407.4×	0.004	C5
complement activation, GZMK pathway	1	1296.3×	0.004	C5
complement activation, alternative pathway	1	991.3×	0.004	C5
complement activation, classical pathway	1	543.6×	0.004	C5
positive regulation of vascular endothelial growth factor production	1	495.6×	0.004	C5
positive regulation of chemokine production	1	374.5×	0.005	C5
killing of cells of another organism	1	271.8×	0.006	C5
chemotaxis	1	135.9×	0.010	C5
cell surface receptor signaling pathway	1	64.1×	0.019	C5
inflammatory response	1	37.7×	0.028	C5
G protein-coupled receptor signaling pathway	1	36.2×	0.028	C5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
C5	OXAPROZIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C5	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OXAPROZIN	4	C5
CARPROFEN	4	C5
SULINDAC	4	C5
RALOXIFENE	4	C5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
C5	25	Binding:25

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C5	3.4.21.43	classical-complement-pathway C3/C5 convertase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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.

Compound	Max phase	Cohort target (bioactivity)
OXAPROZIN	4	C5
CARPROFEN	4	C5
SULINDAC	4	C5
RALOXIFENE	4	C5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	C5
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.