type II complement component 8 deficiency

Summary

type II complement component 8 deficiency (MONDO:0013421) is a disease caused by C8B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: C8B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	type II complement component 8 deficiency
Mondo ID	MONDO:0013421
OMIM	613789
DOID	DOID:0060302
UMLS	C3151080
MedGen	462430
GARD	0010625
Is cancer (heuristic)	no

Also known as: C8 deficiency type II · C8 deficiency, type II · C8B classic complement early component deficiency · C8D2 · classic complement early component deficiency caused by mutation in C8B · complement component 8 deficiency type 2 · complement component 8 deficiency type II · complement component 8 deficiency, type II · Human complement C8-beta deficiency

Data availability: 28 ClinVar variants · 2 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 › type II complement component 8 deficiency

Related subtypes (12): C1 inhibitor deficiency, complement component C1r/C1s deficiency, complement component 2 deficiency, complement component 5 deficiency, complement component 7 deficiency, complement component 6 deficiency, complement component 3 deficiency, complement component C1s 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

28 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 8 pathogenic, 5 conflicting classifications of pathogenicity, 2 benign, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032165	NM_000066.4(C8B):c.27G>A (p.Trp9Ter)	C8B	Pathogenic	criteria provided, multiple submitters, no conflicts
1325387	NM_000066.4(C8B):c.348C>A (p.Cys116Ter)	C8B	Pathogenic	criteria provided, single submitter
17038	NM_000066.4(C8B):c.1282C>T (p.Arg428Ter)	C8B	Pathogenic	criteria provided, multiple submitters, no conflicts
2174163	NM_000066.4(C8B):c.138del (p.Phe47fs)	C8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2184961	NM_000066.4(C8B):c.850C>T (p.Arg284Ter)	C8B	Pathogenic	criteria provided, multiple submitters, no conflicts
35592	NM_000066.4(C8B):c.820C>T (p.Arg274Ter)	C8B	Pathogenic	criteria provided, single submitter
35594	NM_000066.4(C8B):c.271C>T (p.Gln91Ter)	C8B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35595	NM_000066.4(C8B):c.336del (p.Asn113fs)	C8B	Pathogenic	criteria provided, single submitter
35596	NM_000066.4(C8B):c.605del (p.Pro202fs)	C8B	Pathogenic	no assertion criteria provided
35597	NM_000066.4(C8B):c.1041_1047dup (p.Leu350fs)	C8B	Pathogenic	no assertion criteria provided
1167442	NM_000066.4(C8B):c.1398+9C>T	C8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1507317	NM_000066.4(C8B):c.1606G>A (p.Val536Ile)	C8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1511217	NM_000066.4(C8B):c.725G>A (p.Arg242His)	C8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
35593	NM_000066.4(C8B):c.361C>T (p.Arg121Ter)	C8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827970	NM_000066.4(C8B):c.164G>A (p.Ser55Asn)	C8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1405326	NM_000066.4(C8B):c.1438G>A (p.Ala480Thr)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1416965	NM_000066.4(C8B):c.1616G>A (p.Arg539Gln)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1422556	NM_000066.4(C8B):c.444C>G (p.Asp148Glu)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1445328	NM_000066.4(C8B):c.212C>G (p.Ser71Cys)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1511289	NM_000066.4(C8B):c.659C>A (p.Thr220Lys)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1518704	NM_000066.4(C8B):c.407G>A (p.Arg136His)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2159959	NM_000066.4(C8B):c.1381G>T (p.Ala461Ser)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3778972	NM_000066.4(C8B):c.1671C>A (p.Cys557Ter)	C8B	Uncertain significance	criteria provided, single submitter
559594	NM_000066.4(C8B):c.1653G>A (p.Trp551Ter)	C8B	Uncertain significance	criteria provided, single submitter
827971	NM_000066.4(C8B):c.967C>T (p.Arg323Trp)	C8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1167718	NM_000066.4(C8B):c.1355G>C (p.Trp452Ser)	C8B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1168190	NM_000066.4(C8B):c.1622-20A>G	C8B	Benign	criteria provided, multiple submitters, no conflicts
1169777	NM_000066.4(C8B):c.349G>A (p.Gly117Arg)	C8B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
C8B	Strong	Autosomal recessive	type II complement component 8 deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C8B	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
C8B	HGNC:1353	ENSG00000021852	P07358	Complement component C8 beta chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C8B	Complement component C8 beta chain	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)
C8B	Complement	yes		TSP1_rpt, MAC_perforin, LDrepeatLR_classA_rpt

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C8B	95	tissue_specific	yes	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C8B	810

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C8B	P07358	8

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	C8B
Regulation of Complement cascade	1	233.1×	0.004	C8B

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
complement activation, GZMK pathway	1	1296.3×	0.003	C8B
complement activation, alternative pathway	1	991.3×	0.003	C8B
complement activation	1	624.1×	0.003	C8B
complement activation, classical pathway	1	543.6×	0.003	C8B
positive regulation of immune response	1	481.5×	0.003	C8B
killing of cells of another organism	1	271.8×	0.005	C8B
transmembrane transport	1	168.5×	0.007	C8B
immune response	1	47.1×	0.021	C8B

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
C8B	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	C8B
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)
C8B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.