C8B

protein-coding

complement C8 beta chain, the group of Complement system activation components

Gene summary

This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

MANE transcript

NM_000066.4

Inheritance

ClinVar variants

P:44U:207B:128

Top phenotype

Complement component 8 deficiency, type II

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr1:56,929,207-56,974,383

External References & Databases

Ensembl (ENSG00000021852)

Transcript & Mutation Effects

hg38 • Region Span ~45.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

type II complement component 8 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013421

Submitter: Ambry Genetics

type II complement component 8 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013421

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Complement component 8 deficiency, type IIAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial

Refs: 6822660; 8098723; 9476133; 21270745; 22123893

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C8B variants in ClinVar

8 Conditions Cataloged

not providedTotal: 391

Inborn genetic diseasesTotal: 91

not specifiedTotal: 40

Type II complement component 8 deficiencyTotal: 29

C8B-related disorderTotal: 16

C8B-related disordersTotal: 3

Primary ciliary dyskinesiaTotal: 2

Complement component 6 deficiencyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000066.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	107 clinvar	5 clinvar	114
missense			199 clinvar	15 clinvar	1 clinvar	215
nonsense	13 clinvar	4 clinvar	4 clinvar			21
start loss						0
frameshift	17 clinvar	1 clinvar				18
splice donor/acceptor (+/-2bp)		9 clinvar	2 clinvar			11
Total	30	14	207	122	6	379

Highest pathogenic variant AF is 0.0013223792

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000066.4	RefSeq	NP_000057.3	12	MANE Select
ENST00000371237.9	Ensembl	ENSP00000360281.4	12	MANE Select
NM_001278543.2	RefSeq	NP_001265472.2	11	Standard
NM_001278544.2	RefSeq	NP_001265473.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prion diseases - Homo sapiens (human)
Complement and coagulation cascades - Homo sapiens (human)
Systemic lupus erythematosus - Homo sapiens (human)
Amoebiasis - Homo sapiens (human)
Allograft Rejection

Biological Process

immune response
complement activation
complement activation, alternative pathway
complement activation, classical pathway
cytolysis

Molecular Function

protein-containing complex binding

Cellular Component

extracellular region
membrane attack complex
membrane
extracellular exosome
extracellular vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371237
Coding exons: 12
Length: 36931
Individuals with no LoFs: 125315
Homozygous LoFs: 0
Heterozygous LoFs: 433
Defined: 125748
p: 0.00172

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.743	351	314	1.12	0.0000176	3895
Missense (PolyPhen)		110	100.13	1.0985		1296
Synonymous	-2.19	146	116	1.26	0.00000674	1090
Loss of Function	0.109	29	29.6	0.978	0.00000155	364

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00086	rare
Latino/Admixed American	0.0022	0.0022	notable
Ashkenazi Jewish	0.0013	0.0013	notable
East Asian	0.00033	0.00033	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.0026	0.0026	notable
South Asian	0.00056	0.00056	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.;
Disease: DISEASE: Complement component 8 deficiency, 2 (C8D2) [MIM:613789]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.431
RVIS EVS: 0.56
RVIS percentile EVS: 81.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.869

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium