C4BPB

protein-coding

complement component 4 binding protein beta, the group of Complement system regulators and receptors|Sushi domain containing

Gene summary

This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. A single, unique beta-chain encoded by this gene assembles with seven identical alpha-chains into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Alternative splicing gives rise to multiple transcript variants. [provided by RefSeq, Jul 2008]

Previous symbols:

C4BP

MANE transcript

NM_001017365.3

Inheritance

—

ClinVar variants

U:25B:12

Top phenotype

C4BPB-related disorder

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:207,088,860-207,099,993

External References & Databases

Ensembl (ENSG00000123843)

Transcript & Mutation Effects

hg38 • Region Span ~11.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C4BPB variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 6

C4BPB-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001017365.3. 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				6 clinvar	1 clinvar	7
missense			25 clinvar	5 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	25	11	1	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 82 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001017365.3	RefSeq	NP_001017365.1	6	MANE Select
ENST00000367078.8	Ensembl	ENSP00000356045.3	6	MANE Select
NM_000716.3	RefSeq	NP_000707.1	6	Standard
NM_001017364.1	RefSeq	NP_001017364.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Complement and coagulation cascades - Homo sapiens (human)
Pertussis - Homo sapiens (human)
Innate Immune System
Immune System
FOXA1 transcription factor network

Biological Process

complement activation, classical pathway
blood coagulation
regulation of complement activation
innate immune response
positive regulation of protein catabolic process

Molecular Function

protein binding

Cellular Component

extracellular region
extracellular space
plasma membrane
other organism cell

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243611
Coding exons: 6
Length: 11152
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125744
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.463	120	135	0.888	0.00000674	1676
Missense (PolyPhen)		23	33.171	0.69337		433
Synonymous	0.117	48	49.0	0.979	0.00000277	431
Loss of Function	0.870	8	11.1	0.719	5.56e-7	128

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. It also interacts with anticoagulant protein S and with serum amyloid P component. The beta chain binds protein S.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.962
RVIS EVS: 0.13
RVIS percentile EVS: 63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.471

Gene Damage Prediction

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