C4A complement C4A (Chido/Rodgers blood group) [Homo sapiens (human)] - Gene

Summary

Official Symbol: C4Aprovided by HGNC
Official Full Name: complement C4A (Chido/Rodgers blood group)provided by HGNC
Primary source: HGNC:HGNC:1323
See related: Ensembl:ENSG00000244731 MIM:120810; AllianceGenome:HGNC:1323
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: C4; RG; C4S; CO4; C4A2; C4A3; C4A4; C4A6; C4AD; CPAMD2
Summary: This gene encodes the acidic form of complement factor 4, 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 is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
Expression: Biased expression in liver (RPKM 487.9), adrenal (RPKM 99.6) and 7 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 (31982057..32002681)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31835263..31855887)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31949834..31970458)

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
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?

Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.
Title: Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.
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.
Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.
Title: Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.
Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE varepsilon2 for Alzheimer's disease.
Title: Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease.
Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia.
Title: Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia.
Association of complement component 4 with neuroimmune abnormalities in the subventricular zone in schizophrenia and autism spectrum disorders.
Title: Association of complement component 4 with neuroimmune abnormalities in the subventricular zone in schizophrenia and autism spectrum disorders.
Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases.
Title: Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases.
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.

Submit: New GeneRIF Correction See all GeneRIFs (120)

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
Blood group, Chido/Rodgers system MedGen: C1292315 OMIM: 614374 GeneReviews: Not available	not available
Complement component 4a deficiency MedGen: C3280642 OMIM: 614380 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

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

G54031 (e-PCR)
- UniSTS:109413

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

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

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 complement component C1q complex 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 inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic cell clearance	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in blood microparticle	HDA more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement 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 neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: complement C4-A

Names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2; C4A anaphylatoxin; MHC class III region complement; Rodgers form of C4; acidic C4; acidic complement C4; complement C4A (Rodgers blood group); complement component 4A (Rodgers 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_011638.1 RefSeqGene

Range

5001..25624

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_137

mRNA and Protein(s)

NM_001252204.2 → NP_001239133.1 complement C4-A isoform 2 preproprotein

See identical proteins and their annotated locations for NP_001239133.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AL645922, BC146673, DA304049, K02403

Consensus CDS

CCDS59005.1

UniProtKB/TrEMBL

A0A140TA44

Related

ENSP00000420212.1, ENST00000498271.1

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:1542 → 1696

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:1462 → 1524

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
NM_007293.3 → NP_009224.2 complement C4-A isoform 1 preproprotein

See identical proteins and their annotated locations for NP_009224.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL645922, BC016933, BC146673, DA304049, K02403

Consensus CDS

CCDS47404.1

UniProtKB/Swiss-Prot

A6H8M8, A6NHJ5, A7E2V2, B0QZR6, B0V2C8, B2RUT6, B7ZVZ6, P01028, P0C0L4, P78445, Q13160, Q13906, Q14033, Q14835, Q4LE82, Q5JNX2, Q5JQM8, Q6P4R1, Q6U2E5, Q6U2E8, Q6U2F0, Q6U2F3, Q6U2F4, Q6U2F6, Q6U2F8, Q6U2G0, Q96EG2, Q96SA8, Q9NPK5, Q9UIP5

UniProtKB/TrEMBL

A0A0G2JPR0

Related

ENSP00000396688.2, ENST00000428956.7

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