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    C1R complement C1r [ Homo sapiens (human) ]

    Gene ID: 715, updated on 14-Nov-2024

    Summary

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    Official Symbol
    C1Rprovided by HGNC
    Official Full Name
    complement C1rprovided by HGNC
    Primary source
    HGNC:HGNC:1246
    See related
    Ensembl:ENSG00000159403 MIM:613785; AllianceGenome:HGNC:1246
    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
    EDS8; EDSPD1
    Summary
    This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]
    Expression
    Broad expression in liver (RPKM 563.3), gall bladder (RPKM 285.8) and 20 other tissues See more
    Orthologs
    all
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    Genomic context

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    See C1R in Genome Data Viewer
    Location:
    12p13.31
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (7080219..7092445, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (7093689..7105531, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (7187523..7245041, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene zinc finger protein 655 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7167609-7168110 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7168111-7168610 Neighboring gene complement C1s Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7188509-7189008 Neighboring gene Sharpr-MPRA regulatory region 13442 Neighboring gene complement C1r subcomponent like Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:7260830-7262029 Neighboring gene C1RL antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7265863-7266364 Neighboring gene RNA, U6 small nuclear 485, pseudogene Neighboring gene retinol binding protein 5

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
      Title: Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.
    2. C1r Upregulates Production of Matrix Metalloproteinase-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.
      Title: C1r Upregulates Production of Matrix Metalloproteinase-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.
    3. A familial case of periodontal Ehlers-Danlos syndrome lacking skin extensibility and joint hypermobility with a missense mutation in C1R.
      Title: A familial case of periodontal Ehlers-Danlos syndrome lacking skin extensibility and joint hypermobility with a missense mutation in C1R.
    4. C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration.
      Title: C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration.
    5. C1q binding to surface-bound IgG is stabilized by C1r2s2 proteases.
      Title: C1q binding to surface-bound IgG is stabilized by C1r(2)s(2) proteases.
    6. C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.
      Title: C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.
    7. periodontal Ehlers-Danlos syndrome caused by missense mutations in C1R is consistently associated with a leukoencephalopathy
      Title: Periodontal Ehlers-Danlos syndrome is associated with leukoencephalopathy.
    8. The serine protease domains of C1r and C1s are at the periphery of the C1r2s2 tetramer both when alone or within the nonactivated C1 complex. The C1 complex adopts a conformation incompatible with intramolecular activation of C1. Instead, intermolecular proteolytic activation between neighboring C1 complexes bound to a complement-activating surface occurs. Many structurally unrelated molecular patterns can activate C1.
      Title: Structure and activation of C1, the complex initiating the classical pathway of the complement cascade.
    9. We identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Using the Sanger method of DNA sequencing in 14 family members, we confirmed the presence of the mutation in 4 patients with early-onset systemic lupus erythematosus and in an asymptomatic 9-year-old girl. Complement levels were low in sera from patients with truncated C1r protein.
      Title: Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease.
    10. Periodontal Ehlers-Danlos Syndrome in at least the great majority of cases results from specific classes of heterozygous mutations in C1R and C1S.
      Title: Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    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
    Ehlers-Danlos syndrome, periodontal type 1
    MedGen: C4551499 OMIM: 130080 GeneReviews: Periodontal Ehlers-Danlos Syndrome
    		not available

    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

    Potential readthrough

    Included gene: C1RL

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables molecular sequestering activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type peptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in complement activation, classical pathway TAS
    Traceable Author Statement
    more info
    		  
    involved_in immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in zymogen activation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in zymogen activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in blood microparticle HDA PubMed 
    is_active_in blood microparticle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 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
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    complement C1r subcomponent
    Names
    complement component 1, r subcomponent
    NP_001341275.1
    NP_001724.4

    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_062465.1 RefSeqGene

      Range
      5163..16620
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1321

    mRNA and Protein(s)

    1. NM_001354346.2 → NP_001341275.1  complement C1r subcomponent isoform 2 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AC233309, AK298445, BC035220
      Consensus CDS
      CCDS86272.1
      UniProtKB/Swiss-Prot
      A6NJQ8, P00736, Q68D77, Q8J012
      UniProtKB/TrEMBL
      B4DPQ0, F5GZR1
      Related
      ENSP00000444271.3, ENST00000536053.6
      Conserved Domains (5) summary
      smart00020
      Location:477 → 711
      Tryp_SPc; Trypsin-like serine protease
      smart00042
      Location:41 → 152
      CUB; Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein
      pfam00431
      Location:207 → 316
      CUB; CUB domain
      pfam00084
      Location:323 → 385
      Sushi; Sushi repeat (SCR repeat)
      pfam14670
      Location:175 → 203
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    2. NM_001733.7 → NP_001724.4  complement C1r subcomponent isoform 1 preproprotein

      Status: REVIEWED

      Source sequence(s)
      BC035220, M14058
      Consensus CDS
      CCDS81658.1
      UniProtKB/Swiss-Prot
      A6NJQ8, P00736, Q68D77, Q8J012
      UniProtKB/TrEMBL
      A0A3B3ISR2
      Related
      ENSP00000497341.1, ENST00000647956.2
      Conserved Domains (5) summary
      smart00020
      Location:463 → 697
      Tryp_SPc; Trypsin-like serine protease
      smart00042
      Location:27 → 138
      CUB; Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein
      pfam00431
      Location:193 → 302
      CUB; CUB domain
      pfam00084
      Location:309 → 371
      Sushi; Sushi repeat (SCR repeat)
      pfam14670
      Location:161 → 189
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      7080219..7092445 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_021160008.1 Reference GRCh38.p14 PATCHES

      Range
      8674..20131 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      7093689..7105531 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P00736.2 GenPept UniProtKB/Swiss-Prot:P00736

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