The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008] See more...

Aliases for CS Gene

Aliases for CS Gene

  • Citrate Synthase 2 3 5
  • Citrate Synthase, Mitochondrial 3 4
  • Citrate (Si)-Synthase 3 4
  • EC 2.3.3.1 4 50
  • EC 2.3.3 50
  • CS 5

External Ids for CS Gene

Previous GeneCards Identifiers for CS Gene

  • GC12M056540
  • GC12P056603
  • GC12M056382
  • GC12M054951
  • GC12M056666
  • GC12M053704

Summaries for CS Gene

Entrez Gene Summary for CS Gene

  • The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008]

GeneCards Summary for CS Gene

CS (Citrate Synthase) is a Protein Coding gene. Diseases associated with CS include Critical Illness Polyneuropathy and Epidemic Typhus. Among its related pathways are Mitochondrial protein import and Carbon metabolism. Gene Ontology (GO) annotations related to this gene include citrate (Si)-synthase activity.

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CS Gene

Genomics for CS Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CS 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 CS on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the CS gene promoter:
  • GR
  • GR-alpha
  • Nkx2-5
  • PPAR-alpha

Genomic Locations for CS Gene

Latest Assembly
chr12:56,271,699-56,300,391
(GRCh38/hg38)
Size:
28,693 bases
Orientation:
Minus strand

Previous Assembly
chr12:56,665,483-56,694,114
(GRCh37/hg19 by Entrez Gene)
Size:
28,632 bases
Orientation:
Minus strand

chr12:56,665,483-56,694,176
(GRCh37/hg19 by Ensembl)
Size:
28,694 bases
Orientation:
Minus strand

Genomic View for CS Gene

Genes around CS on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for CS Gene

Proteins for CS Gene

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

    Protein Symbol:
    O75390-CISY_HUMAN
    Recommended name:
    Citrate synthase, mitochondrial
    Protein Accession:
    O75390
    Secondary Accessions:
    • Q71UT9
    • Q7KZH0
    • Q96FZ8
    • Q9BWN8

    Protein attributes for CS Gene

    Size:
    466 amino acids
    Molecular mass:
    51712 Da
    Quaternary structure:
    • Homodimer.
    SequenceCaution:
    • Sequence=CAE45911.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
    Miscellaneous:
    • Citrate synthase is found in nearly all cells capable of oxidative metabolism.

    Three dimensional structures from OCA and Proteopedia for CS Gene

neXtProt entry for CS Gene

Selected DME Specific Peptides for CS Gene

O75390:
  • PNVDAHSG
  • GGMRGMKGL
  • RLYLTIH
  • VVPGYGHAVLRK
  • TALNSES
  • DPMFKLV
  • DLIPKEQ
  • IYRNLYR
  • EGIRFRG
  • VVPGYGH
  • ETSVLDP
  • LFWLLVTG
  • SALSDPYL
  • WSRALGFPLERPKSMS
  • YTVLFGV
  • AAKIYRN
  • HSGVLLQY
  • HLVGSALS
  • MDLIAKLP
  • TVLFGVSR
  • GLAGPLHGLANQEVL
  • FGVSRALG
  • VLRKTDPRY
  • RAALPSHVVTML
  • DHEGGNVSAHT
  • LLEQGKAKNPWPNVD
  • GGEEPLPE
  • QREFALKH
  • NFTNMLGY
  • LDWSHNFTNML
  • EPLPEGLFWLL
  • DHEGGNVSAH
  • KYWELIYED
  • SCLVLAARHASASSTNLKD

Post-translational modifications for CS Gene

  • Methylated (PubMed:28391595, PubMed:28887308). Trimethylation at Lys-395 by CSKMT decreases citrate synthase activity (PubMed:28887308).
  • Ubiquitination at Lys43, Lys103, Lys327, Lys382, and Lys459
  • Modification sites at PhosphoSitePlus

Domains & Families for CS Gene

Gene Families for CS Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for CS Gene

GenScript: Design optimal peptide antigens:
  • Citrate synthase (B4DJV2_HUMAN)
  • Citrate synthase, mitochondrial (CISY_HUMAN)
  • Citrate synthase (Q0QEL2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O75390

UniProtKB/Swiss-Prot:

CISY_HUMAN :
  • Belongs to the citrate synthase family.
Family:
  • Belongs to the citrate synthase family.
genes like me logo Genes that share domains with CS: view

Function for CS Gene

Molecular function for CS Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=acetyl-CoA + H2O + oxaloacetate = citrate + CoA + H(+); Xref=Rhea:RHEA:16845, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:16947, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10117};.
GENATLAS Biochemistry:
citrate synthase,mitochondrial,catalyzing the first step of citric acid cycle

Enzyme Numbers (IUBMB) for CS Gene

Phenotypes From GWAS Catalog for CS Gene

Gene Ontology (GO) - Molecular Function for CS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22681889
GO:0004108 citrate (Si)-synthase activity IEA,IDA 9543345
GO:0016740 transferase activity IEA --
GO:0046912 transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer IEA --
genes like me logo Genes that share ontologies with CS: view
genes like me logo Genes that share phenotypes with CS: view

Animal Models for CS Gene

MGI Knock Outs for CS:
  • Cs Cs<tm1.1(KOMP)Wtsi>

Animal Models for research

  • Taconic Biosciences Mouse Models for CS

Inhibitory RNAs for research

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

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CS Gene

Localization for CS Gene

Subcellular locations from UniProtKB/Swiss-Prot for CS Gene

Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
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 CS gene
Compartment Confidence
mitochondrion 5
extracellular 4
nucleus 4
plasma membrane 2
cytoskeleton 2
peroxisome 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus HDA 21630459
GO:0005739 mitochondrion IDA --
GO:0005759 mitochondrial matrix IEA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with CS: view

Pathways & Interactions for CS Gene

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

UniProtKB/Swiss-Prot O75390-CISY_HUMAN

  • Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 1/2.

Gene Ontology (GO) - Biological Process for CS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IBA,IDA 9543345
GO:0006099 tricarboxylic acid cycle IEA,TAS --
GO:0006101 citrate metabolic process IEA --
genes like me logo Genes that share ontologies with CS: view

No data available for SIGNOR curated interactions for CS Gene

Drugs & Compounds for CS Gene

(41) Drugs for CS Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Citric acid Approved, Vet_approved Nutra Target 1606
Water Approved Pharma 0
alpha-Fluoro-carboxymethyldethia coenzyme A complex Experimental Pharma Target 0
D-Malic acid Experimental Pharma Target 0
Nitromethyldethia coenzyme A Experimental Pharma Target 0

(43) Additional Compounds for CS Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
acetyl-coa
  • AcCoA
  • Acetyl coenzyme A
  • S-Acetyl-CoA
  • S-Acetyl-coenzyme A
  • Ac-CoA
72-89-9
Oxalacetic acid
  • 2-Oxobutanedioic acid
  • 2-Oxosuccinic acid
  • 3-Carboxy-3-oxopropanoic acid
  • Keto-succinic acid
  • Ketosuccinic acid
328-42-7
genes like me logo Genes that share compounds with CS: view

Transcripts for CS Gene

mRNA/cDNA for CS Gene

2 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
33 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 CS

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

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b · 6c · 6d ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b ·
SP1: - - - - - - -
SP2: - - -
SP3: - - - - - -
SP4:
SP5: - - - - - -
SP6: - - - - - - - -
SP7: - -
SP8: - - - - - - - - - - -
SP9: - - - - - -
SP10: - - - - - - - - - - -
SP11: - - - - - - - - - - - -
SP12: - - - - - - - - - - - - - -
SP13: - - - -
SP14: -
SP15: - - - -

ExUns: 13c ^ 14 ^ 15 ^ 16 ^ 17
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:

Relevant External Links for CS Gene

GeneLoc Exon Structure for
CS

Expression for CS Gene

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

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

This gene is overexpressed in Heart - Left Ventricle (x4.6) and Muscle - Skeletal (x4.5).

Protein differential expression in normal tissues from HIPED for CS Gene

This gene is overexpressed in Heart (8.7).

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



Protein tissue co-expression partners for CS Gene

- Elite partner

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

SOURCE GeneReport for Unigene cluster for CS Gene:

Hs.743252

Evidence on tissue expression from TISSUES for CS Gene

  • Nervous system(5)
  • Heart(4.8)
  • Liver(4.7)
  • Lung(3.9)
  • Muscle(3.8)
  • Intestine(3.8)
  • Skin(3.8)
  • Kidney(3.5)
  • Eye(3.5)
  • Blood(3.3)
  • Pancreas(3.3)
  • Thyroid gland(2.4)
  • Adrenal gland(2.4)
  • Bone marrow(2.3)
  • Stomach(2.3)
  • Spleen(2.3)
  • Lymph node(2.1)
genes like me logo Genes that share expression patterns with CS: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CS Gene

Orthologs for CS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CS Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CS 29
  • 99.57 (n)
Dog
(Canis familiaris)
Mammalia CS 29 30
  • 93.28 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 93 (a)
OneToMany
-- 30
  • 90 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia CS 29 30
  • 92.92 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Csl 30
  • 90 (a)
OneToMany
Cs 29 16 30
  • 88.74 (n)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Cs 29
  • 89.45 (n)
Chicken
(Gallus gallus)
Aves CS 29 30
  • 77.78 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CS 30
  • 88 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cs 29
  • 77.83 (n)
Str.1513 29
Zebrafish
(Danio rerio)
Actinopterygii cs 30
  • 88 (a)
OneToOne
LOC100536541 29
  • 77.19 (n)
wufb58e04 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG3861 31
  • 73 (a)
kdn 29 30
  • 66.29 (n)
OneToOne
CG14740 31
  • 54 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012048 29
  • 67.56 (n)
Worm
(Caenorhabditis elegans)
Secernentea T20G5.2 31
  • 68 (a)
cts-1 29 30
  • 61.78 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CIT2 29 30
  • 57.67 (n)
OneToOne
CIT1 32
Thale Cress
(Arabidopsis thaliana)
eudicotyledons ATCS 29
  • 61.71 (n)
Soybean
(Glycine max)
eudicotyledons Gma.16706 29
Rice
(Oryza sativa)
Liliopsida Os02g0194100 29
  • 60.47 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 70 (a)
OneToOne
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.5369 29
Species where no ortholog for CS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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)
  • 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)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for CS Gene

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

Paralogs for CS Gene

genes like me logo Genes that share paralogs with CS: view

No data available for Paralogs for CS Gene

Variants for CS Gene

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

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs1004878872 Likely Benign: not provided 56,285,943(-) C/T
NM_004077.3(CS):c.174G>A (p.Thr58=)
SYNONYMOUS
rs139054969 Likely Benign: not provided 56,273,097(-) G/A
NM_004077.3(CS):c.1388C>T (p.Ser463Phe)
MISSENSE
rs141833651 Benign: not provided 56,282,971(-) A/G
NM_004077.3(CS):c.288T>C (p.Phe96=)
SYNONYMOUS
rs61738833 Benign: not provided 56,276,015(-) G/A
NM_004077.3(CS):c.769C>T (p.Leu257=)
SYNONYMOUS

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

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

Structural Variations from Database of Genomic Variants (DGV) for CS Gene

Variant ID Type Subtype PubMed ID
nsv482992 CNV gain+loss 15286789

Variation tolerance for CS Gene

Residual Variation Intolerance Score: 59.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.32; 7.14% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CS Gene

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

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CS Gene

Disorders for CS Gene

MalaCards: The human disease database

(35) MalaCards diseases for CS Gene - From: COP and GCD

Disorder Aliases PubMed IDs
critical illness polyneuropathy
  • polyneuropathy, critical illness
epidemic typhus
  • sylvatic typhus
mitochondrial pyruvate carrier deficiency
  • mpycd
bartonellosis
  • bartonella infectious disease
senile cataract
- elite association - COSMIC cancer census association via MalaCards
Search CS in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CS

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

No data available for UniProtKB/Swiss-Prot and Genatlas for CS Gene

Publications for CS Gene

  1. Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis. (PMID: 17298551) Bonache S … Larriba S (International journal of andrology 2007) 3 22 40
  2. [Cloning and tissue expression pattern analysis of the human citrate synthase cDNA]. (PMID: 12549038) Liu Q … Zhao SY (Shi yan sheng wu xue bao 2000) 3 4 22
  3. Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase. (PMID: 28391595) Rhein VF … Walker JE (FEBS letters 2017) 3 4
  4. Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation. (PMID: 28887308) Małecki J … Falnes PØ (The Journal of biological chemistry 2017) 3 4
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 40

Products for CS Gene

Sources for CS Gene