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Aliases for C1S Gene

Aliases for C1S Gene

  • Complement C1s 2 3 5
  • Complement Component 1, S Subcomponent 2 3
  • Complement Component 1 Subcomponent S 3 4
  • EC 4 58
  • C1 Esterase 3 4
  • Basic Proline-Rich Peptide IB-1 3
  • Complement C1s Subcomponent 3
  • EC 3.4.21 58
  • EDSPD2 3

External Ids for C1S Gene

Previous GeneCards Identifiers for C1S Gene

  • GC12U990009
  • GC12P006975
  • GC12P007038
  • GC12P007096
  • GC12P007028
  • GC12P007042
  • GC12P007182
  • GC12P007229
  • GC12P007283
  • GC12P007328
  • GC12P007377

Summaries for C1S Gene

Entrez Gene Summary for C1S Gene

  • This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]

GeneCards Summary for C1S Gene

C1S (Complement C1s) is a Protein Coding gene. Diseases associated with C1S include Ehlers-Danlos Syndrome, Periodontal Type, 2 and Periodontal Ehlers-Danlos Syndrome. Among its related pathways are Complement Pathway and Staphylococcus aureus infection. GO annotations related to this gene include calcium ion binding and serine-type endopeptidase activity. An important paralog of this gene is MASP1.

UniProtKB/Swiss-Prot for C1S Gene

  • C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.

Gene Wiki entry for C1S Gene

Additional gene information for C1S Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for C1S Gene

Genomics for C1S Gene

Regulatory Elements for C1S Gene

Enhancers for C1S Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12H006923 1.7 FANTOM5 ENCODE dbSUPER 10.9 -61.1 -61109 6.8 HDGF ARID4B SIN3A ZNF2 YY1 ZNF143 FOS DEK PAF1 SP3 ZNF384 CHD4 ENSG00000219410 LRRC23 ENSG00000247853 SCARNA12 EMG1 PHB2 RPL13P5 NCAPD2
GH12H006762 1.8 FANTOM5 ENCODE dbSUPER 9.8 -221.9 -221855 7.2 HDGF PKNOX1 FOXA2 ARNT ZFP64 ARID4B SIN3A FEZF1 ZNF2 ZBTB7B ENSG00000219410 ZNF384 CHD4 NCAPD2 EMG1 ENSG00000247853 PTPN6 SPSB2 GDF3 TNFRSF1A
GH12H006602 1.7 FANTOM5 ENCODE dbSUPER 9.8 -382.5 -382532 7.4 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 ZNF384 ENSG00000219410 ENSG00000247853 CHD4 NOP2 ING4 NCAPD2 SPSB2 EMG1 SCARNA12
GH12H006459 1.4 Ensembl ENCODE dbSUPER 9.8 -526.1 -526116 6.3 HDGF PKNOX1 ZFP64 BMI1 ZNF143 ZNF207 ATF7 ETV6 RUNX3 CREM ZNF384 ENSG00000219410 CHD4 ENSG00000247853 TAPBPL MRPL51 VAMP1 P3H3 NOP2 SCARNA12
GH12H006662 1.2 ENCODE 9.8 -325.0 -325033 2.2 PKNOX1 FOXA2 ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 SLC30A9 ZNF384 CHD4 ENSG00000219410 ENSG00000247853 EMG1 NCAPD2 SPSB2 SCARNA12 NOP2 ENSG00000256967
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around C1S on UCSC Golden Path with GeneCards custom track

Genomic Locations for C1S Gene

Genomic Locations for C1S Gene
82,774 bases
Plus strand

Genomic View for C1S Gene

Genes around C1S on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
C1S Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for C1S Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for C1S Gene

Proteins for C1S Gene

  • Protein details for C1S Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Complement C1s subcomponent
    Protein Accession:
    Secondary Accessions:
    • D3DUT4
    • Q9UCU7
    • Q9UCU8
    • Q9UCU9
    • Q9UCV0
    • Q9UCV1
    • Q9UCV2
    • Q9UCV3
    • Q9UCV4
    • Q9UCV5
    • Q9UM14

    Protein attributes for C1S Gene

    688 amino acids
    Molecular mass:
    76684 Da
    Quaternary structure:
    • C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.

    Three dimensional structures from OCA and Proteopedia for C1S Gene

neXtProt entry for C1S Gene

Selected DME Specific Peptides for C1S Gene


Post-translational modifications for C1S Gene

  • The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
  • Glycosylation at Asn174 and Asn406
  • Modification sites at PhosphoSitePlus

Domains & Families for C1S Gene

Gene Families for C1S Gene

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

Suggested Antigen Peptide Sequences for C1S Gene

GenScript: Design optimal peptide antigens:

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 C1S: view

Function for C1S Gene

Molecular function for C1S Gene

GENATLAS Biochemistry:
complement component 1,s subcomponent,83kDa,tetramerizing with C1r (2C1r,2C1S),activating C2 and C4 after cleavage,classical pathway of C3 activation
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=12.3 uM for complement component C2 (at 37 degrees Celsius) {ECO:0000269 PubMed:11527969}; KM=1.9 uM for complement component C4 (at 37 degrees Celsius) {ECO:0000269 PubMed:11527969}; Note=Less efficient than MASP2 in C4 cleavage.;
UniProtKB/Swiss-Prot CatalyticActivity:
Cleavage of Arg- -Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)- -Lys bond in complement component C2 to form C2a and C2b: the classical pathway C3 convertase.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by SERPING1.
UniProtKB/Swiss-Prot Function:
C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.

Enzyme Numbers (IUBMB) for C1S Gene

Phenotypes From GWAS Catalog for C1S Gene

Gene Ontology (GO) - Molecular Function for C1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity TAS,IEA --
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 2387866
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with C1S: view
genes like me logo Genes that share phenotypes with C1S: view

Human Phenotype Ontology for C1S Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for C1S Gene

Localization for C1S 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 C1S gene
Compartment Confidence
extracellular 5
plasma membrane 2
nucleus 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for C1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0070062 extracellular exosome IDA 23376485
GO:0072562 blood microparticle IDA 22516433
genes like me logo Genes that share ontologies with C1S: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for C1S Gene

Pathways & Interactions for C1S Gene

genes like me logo Genes that share pathways with C1S: view

Gene Ontology (GO) - Biological Process for C1S Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001867 complement activation, lectin pathway IBA --
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0006956 complement activation TAS --
GO:0006958 complement activation, classical pathway TAS,IEA --
genes like me logo Genes that share ontologies with C1S: view

No data available for SIGNOR curated interactions for C1S Gene

Drugs & Compounds for C1S Gene

(33) Drugs for C1S Gene - From: DrugBank, FDA Approved Drugs, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Abciximab Approved Pharma Target 65
Adalimumab Approved Pharma Target 512
Basiliximab Approved, Investigational Pharma Target 140
Cetuximab Approved Pharma Target EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 762
Conestat alfa Approved Pharma Target, inhibitor 0

(7) Additional Compounds for C1S Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with C1S: view

Transcripts for C1S Gene

mRNA/cDNA for C1S Gene

(4) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(10) Selected AceView cDNA sequences:
(21) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for C1S Gene

Complement component 1, s subcomponent:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for C1S Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c · 6d · 6e ^ 7a · 7b · 7c ^ 8a · 8b · 8c ^ 9a · 9b · 9c ·
SP1: - - - - - - -
SP2: - - - - -
SP3: - -
SP4: - - - - - - - - - - - - - - -
SP5: - - - - - - - - - -
SP6: - - - - - - - - - - - - -
SP7: - - - - - - - - - - - - - - - - -
SP9: - - - - - - - - - - -
SP10: - - - - - - - - - - - - -
SP11: - - - - -
SP12: - - -
SP13: - - -
SP14: -
SP15: - - -
SP16: - -
SP18: - - - - -
SP19: - - - - - - - -
SP21: - - - - -

ExUns: 9d · 9e ^ 10a · 10b ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b · 13c ^ 14a · 14b ^ 15a · 15b · 15c ^ 16 ^ 17 ^ 18a · 18b · 18c
SP1: - -
SP2: - -
SP3: -
SP7: - - - -
SP8: - - -

Relevant External Links for C1S Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for C1S Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for C1S Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for C1S Gene

This gene is overexpressed in Liver (x7.6).

Protein differential expression in normal tissues from HIPED for C1S Gene

This gene is overexpressed in Serum (25.9), Plasma (13.3), and Synovial fluid (9.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for C1S Gene

Protein tissue co-expression partners for C1S Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of C1S Gene:


SOURCE GeneReport for Unigene cluster for C1S Gene:


Evidence on tissue expression from TISSUES for C1S Gene

  • Liver(4.9)
  • Nervous system(4.9)
  • Blood(4.6)
  • Lung(4.5)
  • Intestine(4.4)
  • Spleen(4.3)
  • Bone marrow(4)
  • Skin(3.5)
  • Heart(3.1)
  • Stomach(2.8)
  • Kidney(2.7)
  • Gall bladder(2.6)
  • Muscle(2.6)
  • Eye(2.3)
  • Pancreas(2.3)
  • Lymph node(2.2)
  • Adrenal gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for C1S 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 C1S: view

No data available for mRNA Expression by UniProt/SwissProt for C1S Gene

Orthologs for C1S Gene

This gene was present in the common ancestor of chordates.

Orthologs for C1S Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia C1S 33 34
  • 99.18 (n)
(Canis familiaris)
Mammalia C1S 33 34
  • 84.88 (n)
(Rattus norvegicus)
Mammalia C1s 33
  • 80.3 (n)
(Mus musculus)
Mammalia Gm5077 33 34
  • 80.01 (n)
C1s 34
  • 74 (a)
C1s2 16
(Bos Taurus)
Mammalia C1S 33 34
  • 79.99 (n)
(Monodelphis domestica)
Mammalia C1S 34
  • 69 (a)
(Ornithorhynchus anatinus)
Mammalia C1S 34
  • 67 (a)
(Gallus gallus)
Aves C1S 33 34
  • 63.15 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 58 (a)
-- 34
  • 55 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia c1s 33
  • 58.03 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.5153 33
(Danio rerio)
Actinopterygii c1r 34
  • 36 (a)
C1S (3 of 3) 34
  • 35 (a)
C1S (2 of 3) 34
  • 34 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 28 (a)
-- 34
  • 27 (a)
-- 34
  • 26 (a)
-- 34
  • 26 (a)
CSA.10613 34
  • 23 (a)
Species where no ortholog for C1S was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 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)

Evolution for C1S Gene

Gene Tree for C1S (if available)
Gene Tree for C1S (if available)

Paralogs for C1S Gene

Variants for C1S Gene

Sequence variations from dbSNP and Humsavar for C1S Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_077120 Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2) [MIM:617174]
rs121909582 Pathogenic 7,070,184(+) TGGTG(C/T)GGCTG reference, missense
rs886040974 Pathogenic 7,066,591(+) AGAGA(-/TGT)GGTGC cds-indel
rs886040975 Pathogenic 7,066,526(+) TGCCC(C/T)GCCCT reference, missense
rs1000056659 -- 7,066,458(+) ATAGA(A/G)TGAGA intron-variant

Variation tolerance for C1S Gene

Residual Variation Intolerance Score: 26.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.59; 78.06% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for C1S Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for C1S Gene

Disorders for C1S Gene

MalaCards: The human disease database

(23) MalaCards diseases for C1S Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
ehlers-danlos syndrome, periodontal type, 2
  • ehlers-danlos syndrome, periodontal type 2
periodontal ehlers-danlos syndrome
  • ehlers-danlos syndrome, type viii
c1s deficiency
  • complement component c1s deficiency
ehlers-danlos syndrome, periodontal type, 1
  • ehlers-danlos syndrome, type viii
immunodeficiency due to a classical component pathway complement deficiency
  • immunodeficiency due to a c1, c4, or c2 component complement deficiency
- elite association - COSMIC cancer census association via MalaCards
Search C1S in MalaCards View complete list of genes associated with diseases


  • Complement component C1s deficiency (C1SD) [MIM:613783]: A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. {ECO:0000269 PubMed:11390518}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2) [MIM:617174]: A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD2 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. EDSPD2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269 PubMed:27745832}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for C1S Gene

lupus systemic-like syndrome

Relevant External Links for C1S

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with C1S: view

Publications for C1S Gene

  1. X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement. (PMID: 12788922) Gregory LA … Gaboriaud C (The Journal of biological chemistry 2003) 3 4 22 60
  2. Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases. (PMID: 11390518) Dragon-Durey MA … Fridman WH (Journal of immunology (Baltimore, Md. : 1950) 2001) 3 4 22 60
  3. 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 60
  4. Risk of meningioma and common variation in genes related to innate immunity. (PMID: 20406964) Rajaraman P … Inskip PD (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2010) 3 45 60
  5. Polymorphisms in innate immunity genes and risk of childhood leukemia. (PMID: 20438785) Han S … Kang D (Human immunology 2010) 3 45 60

Products for C1S Gene

Sources for C1S Gene

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