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 51
  • EC 2.3.3 51
  • 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 Citrate cycle (TCA cycle) and Glyoxylate and dicarboxylate 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
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J056298 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 -0.4 -362 4.7 SP1 CREB1 GATAD2A CTCF ZBTB33 PRDM10 ZNF629 LEF1 SOX13 IKZF1 ENSG00000257303 IL23A CS lnc-CNPY2-4 NEMP1 BAZ2A ZC3H10 CDK2 RN7SL809P TMEM198B
GH12J056286 Promoter 0.5 EPDnew 600.4 +14.3 14327 0.1 CEBPG CEBPB CS lnc-ANKRD52-3-002 piR-61945-103 lnc-CNPY2-4 COQ10A ENSG00000144785
GH12J056196 Enhancer 0.9 Ensembl ENCODE 10.7 +102.5 102490 5 TEAD4 PRDM10 ZNF629 ZIC2 ZNF600 ZBTB44 ZNF639 JUND ZXDB CEBPB NABP2 SMARCC2 RNF41 SLC39A5 ANKRD52 COQ10A ENSG00000258199 CS ENSG00000257740 IL23A
GH12J056206 Enhancer 0.7 ENCODE 11.2 +92.9 92911 1.9 CTCF PRDM10 JUND FOXA1 ZNF143 REST RAD21 ZNF501 POLR2A TRIM22 SLC39A5 ANKRD52 COQ10A CS ZC3H10 RPL41 RPS26 MYL6B RNF41 lnc-NABP2-3
GH12J056201 Enhancer 0.7 Ensembl 10.7 +98.0 97991 2 NR2C1 KAT8 DPF2 HDAC1 GATAD2B FOXK2 ZNF316 ZBTB40 NR2C2 YY1 SLC39A5 ANKRD52 COQ10A CS IL23A PAN2 MYL6B PHC1P1 lnc-NABP2-3 SMARCC2
- 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

Genomic Locations for CS Gene
chr12:56,271,699-56,300,391
(GRCh38/hg38)
Size:
28,693 bases
Orientation:
Minus strand
chr12:56,665,483-56,694,176
(GRCh37/hg19)
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 Model Products

  • Taconic Biosciences Mouse Models for CS

CRISPR Products

Inhibitory RNA Products

  • 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
endosome 1
lysosome 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 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 Activator, Agonist, Target 1509
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 :

CRISPR Products

Inhibitory RNA Products

  • 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)
  • Muscle(4)
  • Lung(4)
  • Skin(3.9)
  • Intestine(3.9)
  • Kidney(3.6)
  • Eye(3.5)
  • Blood(3.5)
  • Pancreas(3.4)
  • Thyroid gland(2.5)
  • Adrenal gland(2.5)
  • Stomach(2.4)
  • Spleen(2.4)
  • Bone marrow(2.4)
  • Lymph node(2.3)
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 30
  • 99.57 (n)
Dog
(Canis familiaris)
Mammalia CS 30 31
  • 93.28 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 93 (a)
OneToMany
-- 31
  • 90 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia CS 30 31
  • 92.92 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Csl 31
  • 90 (a)
OneToMany
Cs 30 17 31
  • 88.74 (n)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Cs 30
  • 89.45 (n)
Chicken
(Gallus gallus)
Aves CS 30 31
  • 77.78 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CS 31
  • 88 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cs 30
  • 77.83 (n)
Str.1513 30
Zebrafish
(Danio rerio)
Actinopterygii cs 31
  • 88 (a)
OneToOne
LOC100536541 30
  • 77.19 (n)
wufb58e04 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG3861 32
  • 73 (a)
kdn 30 31
  • 66.29 (n)
OneToOne
CG14740 32
  • 54 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012048 30
  • 67.56 (n)
Worm
(Caenorhabditis elegans)
Secernentea T20G5.2 32
  • 68 (a)
cts-1 30 31
  • 61.78 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CIT2 30 31
  • 57.67 (n)
OneToOne
CIT1 33
Thale Cress
(Arabidopsis thaliana)
eudicotyledons ATCS 30
  • 61.71 (n)
Soybean
(Glycine max)
eudicotyledons Gma.16706 30
Rice
(Oryza sativa)
Liliopsida Os02g0194100 30
  • 60.47 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 70 (a)
OneToOne
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.5369 30
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

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
708211 Likely Benign: not provided 56,273,097(-) G/A MISSENSE_VARIANT
728964 Benign: not provided 56,282,971(-) A/G SYNONYMOUS_VARIANT
737271 Likely Benign: not provided 56,285,943(-) C/T SYNONYMOUS_VARIANT
777689 Benign: not provided 56,276,015(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for CS Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for CS Gene

MalaCards: The human disease database

(39) MalaCards diseases for CS Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
critical illness polyneuropathy
  • polyneuropathy, critical illness
epidemic typhus
  • sylvatic typhus
neuroretinitis
  • focal retinitis and retinochoroiditis, juxtapapillary
endemic typhus
  • cat flea rickettsiosis
queensland tick typhus
  • australian tick typhus
- 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

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 23 41
  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 23
  3. 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
  4. Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase. (PMID: 28391595) Rhein VF … Walker JE (FEBS letters 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 41

Products for CS Gene

Sources for CS Gene