C4B complement C4B (Chido/Rodgers blood group) [Homo sapiens (human)] - Gene

Summary

Official Symbol: C4Bprovided by HGNC
Official Full Name: complement C4B (Chido/Rodgers blood group)provided by HGNC
Primary source: HGNC:HGNC:1324
See related: Ensembl:ENSG00000224389 MIM:120820; AllianceGenome:HGNC:1324
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CH; C4F; CO4; C4B1; C4B2; C4B3; C4B5; C4BD; C4B12; C4B_2; CPAMD3
Summary: This gene encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, May 2020]
Expression: Biased expression in liver (RPKM 500.9), adrenal (RPKM 103.5) and 6 other tissues See more
Orthologs: all
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Genomic context

Location:: 6p21.33

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (32014795..32035418)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31868001..31888625)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31982572..32003195)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma.
Title: Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma.
Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Title: Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Plasma Complement 3 and Complement 4 Are Promising Biomarkers for Distinguishing NMOSD From MOGAD and Are Associated With the Blood-Brain-Barrier Disruption in NMOSD.
Title: Plasma Complement 3 and Complement 4 Are Promising Biomarkers for Distinguishing NMOSD From MOGAD and Are Associated With the Blood-Brain-Barrier Disruption in NMOSD.
The BS variant of C4 protects against age-related loss of white matter microstructural integrity.
Title: The BS variant of C4 protects against age-related loss of white matter microstructural integrity.
Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE epsilon2 protective effect in Alzheimer disease.
Title: Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease.
Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects.
Title: Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects.
Association between complement 4 copy number variation and systemic lupus erythematosus: a meta-analysis.
Title: Association between complement 4 copy number variation and systemic lupus erythematosus: a meta-analysis.
Glomerular C4d deposition in proliferative glomerular diseases.
Title: Glomerular C4d deposition in proliferative glomerular diseases.
Complement genes contribute sex-biased vulnerability in diverse disorders.
Title: Complement genes contribute sex-biased vulnerability in diverse disorders.
Employing a range of biochemical approaches, the authors showed (i) a direct association of C1q to Chandipura virus, (ii) deposition of complement proteins C3b, C4b, and C1q on Chandipura virus, and (iii) virus aggregation.
Title: Complement-Mediated Neutralization of a Potent Neurotropic Human Pathogen, Chandipura Virus, Is Dependent on C1q.

Submit: New GeneRIF Correction See all GeneRIFs (130)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Complement component 4b deficiency MedGen: C3280641 OMIM: 614379 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Preincubation of HIV-1 gp41 with either factor H or properdin, and of HIV-1 gp120 with C3b or C4b affect the interaction between HIV-1 gp41 and gp120	PubMed
	env	A synthetic peptide covering positions 233-251 of the HIV-1 gp120 protein binds to complement proteins C3, C4, C5, C9, and properdin	PubMed
	env	Complement proteins C4, C3d, C5b-9, and properdin bind to HIV-1 gp120-coated CD4+ T cells of healthy individuals when incubated in autologous serum	PubMed
	env	Amino acid residues 410-449 of HIV-1 gp120 are involved in its binding to C4b	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

CYP21A2_2362 (e-PCR)
- UniSTS:280636

N3_3_2 (e-PCR)
- UniSTS:239179

GDB:642029 (e-PCR)
- UniSTS:158557

G54031 (e-PCR)
- UniSTS:109413

SHGC-12566 (e-PCR)
- UniSTS:27784

RH11436 (e-PCR)
- UniSTS:85393

G29213 (e-PCR)
- UniSTS:52113

SHGC-31623 (e-PCR)
- UniSTS:9364

WI-7720 (e-PCR)
- UniSTS:38571

RH36425 (e-PCR)
- UniSTS:3021

RH1519 (e-PCR)
- UniSTS:42455

RH46798 (e-PCR)
- UniSTS:42456

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables carbohydrate binding	IDA Inferred from Direct Assay more info	PubMed
enables complement binding	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in complement activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in complement activation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in complement activation, classical pathway	IEA Inferred from Electronic Annotation more info
involved_in detection of molecule of bacterial origin	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in opsonization	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of apoptotic cell clearance	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in blood microparticle	HDA more info	PubMed
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in symbiont cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: complement C4-B

Names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3; Chido form of C4; basic complement C4; complement C4B (Chido blood group); complement C4B1a; complement component 4B (Chido blood group)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011639.1 RefSeqGene

Range

5002..25625

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_138

mRNA and Protein(s)

NM_001002029.4 → NP_001002029.3 complement C4-B preproprotein

See identical proteins and their annotated locations for NP_001002029.3

Status: REVIEWED

Source sequence(s)

AL645922

Consensus CDS

CCDS47405.1

UniProtKB/Swiss-Prot

A2BHY4, P0C0L5, Q6U2E9, Q6U2G1, Q6U2I5, Q6U2L1, Q6U2L7, Q6U2L9, Q6U2M5, Q6VCV8, Q96SA7

UniProtKB/TrEMBL

A0A0G2JPR0

Related

ENSP00000415941.2, ENST00000435363.7

Conserved Domains (8) summary

cd00017
Location:686 → 750

ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...

cd02896
Location:996 → 1315

complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...

cd03584
Location:1588 → 1742

NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...

pfam00207
Location:782 → 869

A2M; Alpha-2-macroglobulin family

pfam01835
Location:141 → 233

A2M_N; MG2 domain

pfam07677
Location:1481 → 1570

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1051 → 1317

A2M_comp; A-macroglobulin complement component

pfam07703
Location:478 → 610

A2M_N_2; Alpha-2-macroglobulin family N-terminal region