Immunodeficiency due to a late component of complement deficiency

Summary

Immunodeficiency due to a late component of complement deficiency (MONDO:0015700) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency due to a late component of complement deficiency
Mondo ID	MONDO:0015700
Orphanet	169150
ICD-11	531050218
UMLS	C0398765
MedGen	585067
GARD	0017050
Is cancer (heuristic)	no

Also known as: deficiency of complement of terminal pathway · immunodeficiency due to a C5 to C9 component complement deficiency · immunodeficiency due to C5 to C9 component complement deficiency · terminal complement pathway deficiency

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 6 Mondo subtypes.

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

Related subtypes (7): classic complement early component deficiency, complement factor I deficiency, recurrent Neisseria infections due to factor D deficiency, immunodeficiency due to a classical component pathway complement deficiency, atypical hemolytic-uremic syndrome, complement receptor deficiency, disorder of lectin complement activation pathway

Subtypes (6): complement component 5 deficiency, complement component 7 deficiency, complement component 6 deficiency, type II complement component 8 deficiency, type I complement component 8 deficiency, complement component 9 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
505659	NM_000065.5(C6):c.1879del (p.Asp627fs)	C6	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C6	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
C6	HGNC:1339	ENSG00000039537	P13671	Complement component C6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C6	Complement component C6	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: 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)
C6	Complement	yes		Sushi_SCR_CCP_dom, TSP1_rpt, MAC_perforin

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
heart right ventricle	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C6	173	tissue_specific	marker	right lobe of liver, liver, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C6	738

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C6	P13671	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.001	C6
Regulation of Complement cascade	1	233.1×	0.004	C6

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
positive regulation of activation of membrane attack complex	1	5617.3×	0.002	C6
complement activation, GZMK pathway	1	1296.3×	0.003	C6
complement activation	1	624.1×	0.004	C6
complement activation, classical pathway	1	543.6×	0.004	C6
positive regulation of immune response	1	481.5×	0.004	C6
killing of cells of another organism	1	271.8×	0.006	C6
transmembrane transport	1	168.5×	0.008	C6
positive regulation of angiogenesis	1	115.4×	0.010	C6
in utero embryonic development	1	72.0×	0.014	C6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	C6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
C6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.