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. [prov... See more...

Aliases for C1R Gene

Aliases for C1R Gene

  • Complement C1r 2 3 5
  • Complement Component 1, R Subcomponent 2 3
  • Complement C1r Subcomponent 3 4
  • EC 4 50
  • Complement Component 1 Subcomponent R 4
  • EC 3.4.21 50
  • EDSPD1 3
  • C1R 5

External Ids for C1R Gene

Previous GeneCards Identifiers for C1R Gene

  • GC12M007198
  • GC12M007376
  • GC12M007067
  • GC12M007057
  • GC12M007058
  • GC12M007133
  • GC12M007047
  • GC12M007187
  • GC12M007081
  • GC12M007092
  • GC12M007098
  • GC12M007095
  • GC12M007110
  • GC12M007088
  • GC12M007135
  • GC12M007156

Summaries for C1R Gene

Entrez Gene Summary for C1R Gene

  • 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]

GeneCards Summary for C1R Gene

C1R (Complement C1r) is a Protein Coding gene. Diseases associated with C1R include Ehlers-Danlos Syndrome, Periodontal Type, 1 and Periodontal Ehlers-Danlos Syndrome. Among its related pathways are Complement and coagulation cascades and Creation of C4 and C2 activators. Gene Ontology (GO) annotations related to this gene include calcium ion binding and serine-type peptidase activity. An important paralog of this gene is C1S.

UniProtKB/Swiss-Prot Summary for C1R Gene

  • C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.

Gene Wiki entry for C1R Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for C1R Gene

Genomics for C1R Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for C1R Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around C1R on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for C1R

Top Transcription factor binding sites by QIAGEN in the C1R gene promoter:
  • C/EBPbeta
  • GATA-1
  • GATA-2
  • GATA-3
  • Ik-2
  • IRF-1
  • NF-1
  • NF-1/L
  • NF-kappaB
  • NF-kappaB1

Genomic Locations for C1R Gene

Latest Assembly
12,327 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
57,519 bases
Minus strand

(GRCh37/hg19 by Ensembl)
57,691 bases
Minus strand

Alternative Locations (GRCh38/hg38)

  • chr12(PATCHES):8,674-20,131 (-)

Genomic View for C1R Gene

Genes around C1R on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
C1R Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for C1R Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for C1R Gene

Proteins for C1R Gene

  • Protein details for C1R Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Complement C1r subcomponent
    Protein Accession:
    Secondary Accessions:
    • A6NJQ8
    • Q68D77
    • Q8J012

    Protein attributes for C1R Gene

    705 amino acids
    Molecular mass:
    80119 Da
    Quaternary structure:
    • C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds.

    Three dimensional structures from OCA and Proteopedia for C1R Gene

neXtProt entry for C1R Gene

Selected DME Specific Peptides for C1R Gene


Post-translational modifications for C1R Gene

  • The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
  • Glycosylation at Asn125, Asn221, Asn514, and Asn581
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • C1R_HUMAN (713)

Domains & Families for C1R Gene

Gene Families for C1R Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for C1R Gene

  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature
  • CUB domain
  • Aspartic acid and asparagine hydroxylation site
  • EGF-like calcium-binding
  • Sushi domain/SCR domain/CCP module

Suggested Antigen Peptide Sequences for C1R Gene

GenScript: Design optimal peptide antigens:
  • Complement component 1 subcomponent r (C1R_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase S1 family.
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with C1R: view

Function for C1R Gene

Molecular function for C1R Gene

UniProtKB/Swiss-Prot Function:
C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC; EC=;.
GENATLAS Biochemistry:
complement component 1,r subcomponent,83kDa,tetramerizing C1s (2C1r,2C1s) possessing a proteinase activity to C1s,classical pathway of C3 activation,see C1Q@

Enzyme Numbers (IUBMB) for C1R Gene

Phenotypes From GWAS Catalog for C1R Gene

Gene Ontology (GO) - Molecular Function for C1R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA,IBA 21873635
GO:0005509 calcium ion binding IEA,IDA 20178990
GO:0005515 protein binding IPI 2387866
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA,TAS 2834284
genes like me logo Genes that share ontologies with C1R: view
genes like me logo Genes that share phenotypes with C1R: view

Human Phenotype Ontology for C1R Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for C1R Gene

MGI Knock Outs for C1R:
  • C1ra C1ra<tm1.1(KOMP)Vlcg>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for C1R

No data available for Transcription Factor Targets and HOMER Transcription for C1R Gene

Localization for C1R Gene

Subcellular locations from UniProtKB/Swiss-Prot for C1R Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for C1R gene
Compartment Confidence
extracellular 5
plasma membrane 4
nucleus 3
cytosol 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for C1R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS, NAS --
GO:0005615 extracellular space IDA, IBA 20178990
GO:0070062 extracellular exosome HDA 23533145
GO:0072562 blood microparticle IBA, HDA 21873635
genes like me logo Genes that share ontologies with C1R: view

Pathways & Interactions for C1R Gene

genes like me logo Genes that share pathways with C1R: view

Pathways by source for C1R Gene

1 GeneGo (Thomson Reuters) pathway for C1R Gene
  • Immune response Classical complement pathway
2 Qiagen pathways for C1R Gene
  • Classical Complement Pathway
  • Complement Pathway

SIGNOR curated interactions for C1R Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for C1R Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0006955 immune response TAS 737019
GO:0006956 complement activation TAS --
GO:0006958 complement activation, classical pathway IEA,TAS --
genes like me logo Genes that share ontologies with C1R: view

Drugs & Compounds for C1R Gene

(13) Drugs for C1R Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Conestat alfa Approved, Investigational Pharma Target, inhibitor 0
Human C1-esterase inhibitor Approved Pharma Target, inhibitor 0
Palivizumab Approved, Investigational Pharma Target 28
Zinc Approved, Investigational Pharma Target 1706
zinc acetate Approved, Investigational Pharma Target 0
genes like me logo Genes that share compounds with C1R: view

Transcripts for C1R Gene

mRNA/cDNA for C1R Gene

11 NCBI additional mRNA sequence :
16 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for C1R

Alternative Splicing Database (ASD) splice patterns (SP) for C1R Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b · 4c · 4d · 4e ^ 5a · 5b ^ 6a · 6b · 6c · 6d · 6e · 6f · 6g ^ 7a · 7b · 7c ^ 8 ^ 9a ·
SP1: - - - -
SP2: - -
SP3: - - - - - -
SP4: - - - - - -
SP5: - - - - - -
SP6: - - -
SP7: - -
SP8: -
SP9: - - - - -

ExUns: 9b

Relevant External Links for C1R Gene

GeneLoc Exon Structure for

Expression for C1R Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for C1R Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for C1R Gene

This gene is overexpressed in Liver (x7.7).

Protein differential expression in normal tissues from HIPED for C1R Gene

This gene is overexpressed in Plasma (23.7), Serum (23.6), and Synovial fluid (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for C1R Gene

Protein tissue co-expression partners for C1R Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for C1R

SOURCE GeneReport for Unigene cluster for C1R Gene:


Evidence on tissue expression from TISSUES for C1R Gene

  • Liver(4.8)
  • Intestine(4.6)
  • Skin(4.6)
  • Bone marrow(4.4)
  • Spleen(3.2)
  • Lymph node(3.2)
  • Lung(3.1)
  • Pancreas(3.1)
  • Heart(3.1)
  • Nervous system(3.1)
  • Kidney(3)
  • Muscle(3)
  • Blood(2.9)
  • Gall bladder(2.7)
  • Adrenal gland(2.6)
  • Stomach(2.6)
  • Eye(2.5)
  • Bone(2.2)
  • Thyroid gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for C1R Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cheek
  • ear
  • eye
  • face
  • head
  • lip
  • meninges
  • mouth
  • neck
  • scalp
  • thyroid
  • bronchus
  • esophagus
  • heart
  • lung
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
  • spleen
  • stomach
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
  • blood
  • blood vessel
  • coagulation system
  • lymph node
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with C1R: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt for C1R Gene

Orthologs for C1R Gene

This gene was present in the common ancestor of chordates.

Orthologs for C1R Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia C1R 29 30
  • 99.57 (n)
(Canis familiaris)
Mammalia C1R 29 30
  • 87.2 (n)
(Rattus norvegicus)
Mammalia C1r 29
  • 83.97 (n)
(Mus musculus)
Mammalia C1ra 29 16 30
  • 83.62 (n)
C1rb 16 30
  • 72 (a)
(Bos Taurus)
Mammalia -- 30
  • 78 (a)
C1R 30
  • 73 (a)
(Monodelphis domestica)
Mammalia -- 30
  • 64 (a)
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 61 (a)
(Gallus gallus)
Aves C1R 29
  • 65.75 (n)
-- 30
  • 58 (a)
(Anolis carolinensis)
Reptilia -- 30
  • 55 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100498646 29
  • 59.48 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 28 (a)
-- 30
  • 28 (a)
-- 30
  • 26 (a)
-- 30
  • 23 (a)
CSA.10613 30
  • 20 (a)
Species where no ortholog for C1R was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for C1R Gene

Gene Tree for C1R (if available)
Gene Tree for C1R (if available)
Evolutionary constrained regions (ECRs) for C1R: view image
Alliance of Genome Resources:
Additional Orthologs for C1R

Paralogs for C1R Gene

(33) SIMAP similar genes for C1R Gene using alignment to 13 proteins:

  • F5H1N6_HUMAN
  • F5H1V0_HUMAN
  • F5H2D0_HUMAN
  • F5H3A3_HUMAN
  • F5H3N3_HUMAN
  • F5H6Y3_HUMAN
  • F6T9X8_HUMAN
genes like me logo Genes that share paralogs with C1R: view

Variants for C1R Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for C1R Gene

Complement component C1r deficiency [MIM:216950] leads to the failure of the classical complement system activation pathway (C1 deficiency). Individuals with C1 deficiency are highly susceptible to infections by microorganisms and have greater risk in developing autoimmune diseases such as systemic lupus erythematosus (SLE).

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for C1R Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
1012818 Likely Benign: not provided 7,088,679(-) G/A
NM_001733.7(C1R):c.969C>T (p.Asn323=)
1012819 Uncertain Significance: not provided 7,088,695(-) A/C
NM_001733.7(C1R):c.953T>G (p.Phe318Cys)
1013005 Likely Benign: not provided 7,091,657(-) G/A
NM_001733.7(C1R):c.26C>T (p.Pro9Leu)
931271 Uncertain Significance: Ehlers-Danlos syndrome, type 8 7,089,415(-) G/T
NM_001733.7(C1R):c.646C>A (p.Pro216Thr)
972707 Likely Pathogenic: Ehlers-Danlos syndrome 7,090,215(-) A/G
NM_001733.7(C1R):c.265T>C (p.Cys89Arg)

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for C1R Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for C1R Gene

Gene Damage Index Score: 7.67; 82.90% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for C1R Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Structural Variations from Database of Genomic Variants (DGV) for C1R Gene

Disorders for C1R Gene

MalaCards: The human disease database

(20) MalaCards diseases for C1R Gene - From: OMI, CVR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search C1R in MalaCards View complete list of genes associated with diseases


  • Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1) [MIM:130080]: A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD1 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD1 inheritance is autosomal dominant. {ECO:0000269 PubMed:27745832}. Note=The disease is caused by variants affecting the gene represented in this entry.

Genatlas disease for C1R Gene

lupus systemic-like syndrome

Additional Disease Information for C1R

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with C1R: view

Publications for C1R Gene

  1. Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement. (PMID: 27745832) Kapferer-Seebacher I … Zschocke J (American journal of human genetics 2016) 3 4 72
  2. The human complement component C1R gene: the exon-intron structure and the molecular basis of allelic diversity. (PMID: 12914573) Nakagawa M … Umetsu K (Annals of human genetics 2003) 3 4 22
  3. Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease. (PMID: 28544690) Demirkaya E … Aksentijevich I (Arthritis & rheumatology (Hoboken, N.J.) 2017) 3 72
  4. Analysis of human C1q by combined bottom-up and top-down mass spectrometry: detailed mapping of post-translational modifications and insights into the C1r/C1s binding sites. (PMID: 20008834) Pflieger D … Daniel R (Molecular & cellular proteomics : MCP 2010) 3 22
  5. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PMID: 16335952) Liu T … Smith RD (Journal of proteome research 2005) 3 4

Products for C1R Gene

Sources for C1R Gene