C4B Gene

HGNC Family Blood group antigens, Complement system
Name complement component 4B (Chido blood group)
Description 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]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Complement component 4 (C4) is expressed as two isoforms—C4A and C4B—that participate in the classical branch of the complement cascade. Genetic variability in the C4 locus gives rise to structurally distinct alleles that differentially govern protein expression levels in the brain and peripheral tissues. For instance, studies in schizophrenia have shown that common alleles produce widely varying levels of C4A and C4B in the brain, with these proteins localizing to neuronal compartments and contributing to synaptic elimination during postnatal development; although the risk association with schizophrenia appears most directly related to elevated C4A expression, the overall complement activity is shaped by both isoforms (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of systemic autoimmunity, assessment of gene copy-number variation has revealed that the repertoire of C4 genes, where long gene forms correlate with C4A and short forms with C4B, influences disease susceptibility. Patients with systemic lupus erythematosus tend to show a shift toward lower total C4 and, in particular, fewer copies of C4A, underscoring the complex interplay between the two isoforms in the regulation of complement activation and maintenance of immune tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings indicate that C4B—along with C4A—functions as a critical mediator of classical pathway activation, opsonization, and inflammatory regulation. Its variable expression contributes not only to neural circuit refinement during development but also to the fine balance between effective immune defense and autoimmunity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aswin Sekar, Allison R Bialas, Heather de Rivera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Schizophrenia risk from complex variation of complement component 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature16549"}], "href": "https://doi.org/10.1038/nature16549"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26814963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26814963"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yan Yang, Erwin K Chung, Yee Ling Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/518257"}], "href": "https://doi.org/10.1086/518257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17503323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17503323"}]}]}]}
Synonyms C4B2, CH, CPAMD3, C4BD, C4B1, C4B_2, C4B5, C4F, C4B3, C4B12
Proteins CO4B_HUMAN
NCBI Gene ID 721
API
Download Associations
Predicted Functions View C4B's ARCHS4 Predicted Functions.
Co-expressed Genes View C4B's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View C4B's ARCHS4 Predicted Functions.

Functional Associations

C4B has 4,765 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 86 datasets.

Click the + buttons to view associations for C4B from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of C4B gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of C4B gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of C4B gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of C4B gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with C4B gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of C4B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of C4B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of C4B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of C4B gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing C4B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing C4B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with C4B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with C4B protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with C4B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with C4B gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with C4B gene/protein from the curated CTD Gene-Disease Associations dataset.
DISEASES Curated Gene-Disease Association Evidence Scores diseases involving C4B gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving C4B gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with C4B gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with C4B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with C4B gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with C4B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with C4B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
DrugBank Drug Targets interacting drugs for C4B protein from the curated DrugBank Drug Targets dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at C4B gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of C4B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of C4B gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing C4B from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with C4B gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with C4B gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with C4B gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing C4B from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of C4B gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of C4B gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of C4B gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GlyGen Glycosylated Proteins ligands (chemical) binding C4B protein from the GlyGen Glycosylated Proteins dataset.
GO Biological Process Annotations 2023 biological processes involving C4B gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving C4B gene from the curated GO Biological Process Annotations2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of C4B gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of C4B gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of C4B gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of C4B gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of C4B gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with C4B gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of C4B gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of C4B gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of C4B protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of C4B gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPM Cell Type and Tissue Protein Expression Profiles cell types and tissues with high or low expression of C4B protein relative to other cell types and tissues from the HPM Cell Type and Tissue Protein Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for C4B from the curated Hub Proteins Protein-Protein Interactions dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with C4B gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by C4B gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of C4B gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of C4B gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEGG Pathways pathways involving C4B protein from the KEGG Pathways dataset.
KEGG Pathways 2026 pathways involving C4B protein from the KEGG Pathways 2026 dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of C4B gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of C4B gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with C4B gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of C4B gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Curated Protein Localization Annotations cellular components containing C4B protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain C4B protein from the LOCATE Predicted Protein Localization Annotations dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of C4B gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of C4B gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing C4B protein recovered by IP-MS from the NURSA Protein Complexes dataset.
OMIM Gene-Disease Associations phenotypes associated with C4B gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for C4B from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of C4B gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving C4B protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving C4B protein from the Wikipathways PFOCR 2024 dataset.
Reactome Pathways 2014 pathways involving C4B protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving C4B protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of C4B gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of C4B gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of C4B gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of C4B gene from the RummaGEO Gene Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of C4B gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of C4B gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of C4B protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of C4B protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of C4B protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of C4B protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with C4B protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with C4B protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving C4B protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving C4B protein from the WikiPathways Pathways 2024 dataset.