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C6 complement C6 [ Homo sapiens (human) ]

Gene ID: 729, updated on 27-Nov-2024

Summary

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Official Symbol
C6provided by HGNC
Official Full Name
complement C6provided by HGNC
Primary source
HGNC:HGNC:1339
See related
Ensembl:ENSG00000039537 MIM:217050; AllianceGenome:HGNC:1339
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
Summary
This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]
Expression
Biased expression in liver (RPKM 126.4), heart (RPKM 11.8) and 2 other tissues See more
Orthologs
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Genomic context

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Location:
5p13.1
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (41142116..41261469, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (41398594..41517945, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (41142218..41261571, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:40916273-40916808 Neighboring gene RNA, U7 small nuclear 161 pseudogene Neighboring gene complement C7 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:41008527-41009726 Neighboring gene maestro heat like repeat family member 2B Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:41064203-41064771 Neighboring gene uncharacterized LOC105374739 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:41122112-41123311 Neighboring gene NANOG hESC enhancer GRCh37_chr5:41230420-41230921 Neighboring gene NANOG hESC enhancer GRCh37_chr5:41252597-41253129 Neighboring gene uncharacterized LOC124900969 Neighboring gene uncharacterized LOC102723740 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15985 Neighboring gene phosphatidylinositol specific phospholipase C X domain containing 3 Neighboring gene uncharacterized LOC105374740

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Characterization of the human C6 promoter: requirement of the CCAAT enhancer binding protein binding site for C6 gene promoter activity. González S, et al. J Immunol, 1996 Sep 15. PMID 8805625
  2. Polymorphism of human complement component C6: an amino acid substitution (Glu/Ala) within the second thrombospondin repeat differentiates between the two common allotypes C6 A and C6 B. Dewald G, et al. Biochem Biophys Res Commun, 1993 Jul 15. PMID 8101442
  3. Synthesis of complement components C5, C6, C7, C8 and C9 in vitro by human monocytes and assembly of the terminal complement complex. Hetland G, et al. Scand J Immunol, 1986 Oct. PMID 3764345
  4. Association analysis of C6 genetic variations and aspirin hypersensitivity in Korean asthmatic patients. Pasaje CF, et al. Hum Immunol, 2011 Oct. PMID 21704099
  5. Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC). Aleshin AE, et al. J Biol Chem, 2012 Mar 23. PMID 22267737, Free PMC Article

See all (62) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
    Title: Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
  2. specific association of NR1I3, C6 and TNN with low hip BMD risk
    Title: Multiple analyses indicate the specific association of NR1I3, C6 and TNN with low hip BMD risk.
  3. Our study provided novel evidence that genetic variations in complement genes C6 and MASP1were associated with preeclampsia risk, and that the risk varied by preeclampsia subtypes
    Title: Polymorphisms in complement genes and risk of preeclampsia in Taiyuan, China.
  4. recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models.
    Title: Recipient C6 rs9200 genotype is associated with hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population.
  5. Complement C5b-9 complex sensitizes 661W photoreceptor cells to both apoptosis and necroptosis.
    Title: Exposure to the complement C5b-9 complex sensitizes 661W photoreceptor cells to both apoptosis and necroptosis.
  6. Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex.
    Title: Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex.
  7. Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC).
    Title: Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC).
  8. finding of very high serious morbidity in patients with complete C6 deficiency due to meningococcal infections
    Title: Complete deficiency of the sixth complement component (C6Q0), susceptibility to Neisseria meningitidis infections and analysis of the frequencies of C6Q0 gene defects in South Africans.
  9. Genetic polymorphisms in C6 gene do not influence the risk of aspirin hypersensitivity in Korean asthmatic patients.
    Title: Association analysis of C6 genetic variations and aspirin hypersensitivity in Korean asthmatic patients.
  10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Submit: New GeneRIF Correction See all GeneRIFs (16)

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 6 deficiency
MedGen: C2676232 OMIM: 612446 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in in utero embryonic development IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in killing of cells of another organism IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of immune response NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of membrane attack complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of membrane attack complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of membrane attack complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
complement component C6
Names
complement component 6

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

  1. NG_011582.1 RefSeqGene

    Range
    5001..124293
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_29

mRNA and Protein(s)

  1. NM_000065.5 → NP_000056.2  complement component C6 precursor

    See identical proteins and their annotated locations for NP_000056.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript. Variants 1 and 2 both encode the same protein.
    Source sequence(s)
    AC008863, DA642358, J05064
    Consensus CDS
    CCDS3936.1
    UniProtKB/Swiss-Prot
    P13671
    UniProtKB/TrEMBL
    A8K8Z4
    Related
    ENSP00000338861.5, ENST00000337836.10
    Conserved Domains (7) summary
    cd00033
    Location:644 → 700
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    smart00032
    Location:704 → 755
    CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
    smart00057
    Location:862 → 934
    FIMAC; factor I membrane attack complex
    smart00209
    Location:568 → 623
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 127
    TSP_1; Thrombospondin type 1 domain

  2. NM_001115131.4 → NP_001108603.2  complement component C6 precursor

    See identical proteins and their annotated locations for NP_001108603.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein.
    Source sequence(s)
    AC008863, AC091871, BC035723, BJ993387, J05064
    Consensus CDS
    CCDS3936.1
    UniProtKB/Swiss-Prot
    P13671
    UniProtKB/TrEMBL
    A8K8Z4
    Related
    ENSP00000263413.3, ENST00000263413.7
    Conserved Domains (7) summary
    cd00033
    Location:644 → 700
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    smart00032
    Location:704 → 755
    CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
    smart00057
    Location:862 → 934
    FIMAC; factor I membrane attack complex
    smart00209
    Location:568 → 623
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 127
    TSP_1; Thrombospondin type 1 domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    41142116..41261469 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047417689.1 → XP_047273645.1  complement component C6 isoform X5

  2. XM_011514119.4 → XP_011512421.1  complement component C6 isoform X4

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:653 → 709
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    smart00032
    Location:713 → 764
    CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
    smart00057
    Location:880 → 952
    FIMAC; factor I membrane attack complex
    smart00209
    Location:577 → 632
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:322 → 523
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:151 → 182
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:94 → 142
    TSP_1; Thrombospondin type 1 domain

  3. XM_006714496.5 → XP_006714559.1  complement component C6 isoform X3

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:672 → 728
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    smart00032
    Location:732 → 783
    CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:596 → 651
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:322 → 523
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:151 → 182
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cl15278
    Location:94 → 136
    TSP_1; Thrombospondin type 1 domain

  4. XM_011514114.4 → XP_011512416.1  complement component C6 isoform X1

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:672 → 728
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    smart00032
    Location:732 → 783
    CCP; Domain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
    smart00057
    Location:899 → 971
    FIMAC; factor I membrane attack complex
    smart00209
    Location:596 → 651
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:322 → 523
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:151 → 182
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    cl15278
    Location:94 → 136
    TSP_1; Thrombospondin type 1 domain

  5. XM_011514115.4 → XP_011512417.1  complement component C6 isoform X2

    See identical proteins and their annotated locations for XP_011512417.1

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:663 → 719
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    PHA02831
    Location:663 → 785
    PHA02831; EEV host range protein; Provisional
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:587 → 642
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 133
    TSP_1; Thrombospondin type 1 domain

  6. XM_011514116.4 → XP_011512418.1  complement component C6 isoform X2

    See identical proteins and their annotated locations for XP_011512418.1

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:663 → 719
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    PHA02831
    Location:663 → 785
    PHA02831; EEV host range protein; Provisional
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:587 → 642
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 133
    TSP_1; Thrombospondin type 1 domain

  7. XM_047417687.1 → XP_047273643.1  complement component C6 isoform X2

  8. XM_011514117.4 → XP_011512419.1  complement component C6 isoform X2

    See identical proteins and their annotated locations for XP_011512419.1

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:663 → 719
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    PHA02831
    Location:663 → 785
    PHA02831; EEV host range protein; Provisional
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:587 → 642
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 133
    TSP_1; Thrombospondin type 1 domain

  9. XM_017009818.3 → XP_016865307.1  complement component C6 isoform X2

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:663 → 719
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    PHA02831
    Location:663 → 785
    PHA02831; EEV host range protein; Provisional
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:587 → 642
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 133
    TSP_1; Thrombospondin type 1 domain

  10. XM_011514118.4 → XP_011512420.1  complement component C6 isoform X2

    See identical proteins and their annotated locations for XP_011512420.1

    UniProtKB/TrEMBL
    A8K8Z4
    Conserved Domains (7) summary
    cd00033
    Location:663 → 719
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    PHA02831
    Location:663 → 785
    PHA02831; EEV host range protein; Provisional
    smart00057
    Location:890 → 962
    FIMAC; factor I membrane attack complex
    smart00209
    Location:587 → 642
    TSP1; Thrombospondin type 1 repeats
    smart00457
    Location:313 → 514
    MACPF; membrane-attack complex / perforin
    cd00112
    Location:142 → 173
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...
    pfam00090
    Location:85 → 133
    TSP_1; Thrombospondin type 1 domain

  11. XM_047417688.1 → XP_047273644.1  complement component C6 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    41398594..41517945 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054353424.1 → XP_054209399.1  complement component C6 isoform X5

  2. XM_054353423.1 → XP_054209398.1  complement component C6 isoform X4

  3. XM_054353417.1 → XP_054209392.1  complement component C6 isoform X3

  4. XM_054353415.1 → XP_054209390.1  complement component C6 isoform X1

  5. XM_054353416.1 → XP_054209391.1  complement component C6 isoform X2

  6. XM_054353421.1 → XP_054209396.1  complement component C6 isoform X2

  7. XM_054353420.1 → XP_054209395.1  complement component C6 isoform X2

  8. XM_054353419.1 → XP_054209394.1  complement component C6 isoform X2

  9. XM_054353418.1 → XP_054209393.1  complement component C6 isoform X2

  10. XM_054353422.1 → XP_054209397.1  complement component C6 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P13671.3 GenPept UniProtKB/Swiss-Prot:P13671

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