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    C6 complement C6 [ Homo sapiens (human) ]

    Gene ID: 729, updated on 2-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
    mouse all
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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 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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