CS

citrate synthase

Basic information

Region (hg38): 12:56271698-56300391

Links

ENSG00000062485 ∙ NCBI:1431 ∙ OMIM:118950 ∙ HGNC:2422 ∙ Uniprot:O75390 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CS gene.

• Inborn genetic diseases (9 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	1	2

Variants in CS

This is a list of pathogenic ClinVar variants found in the CS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-56273097-G-A		not specified	Conflicting classifications of pathogenicity (Jun 03, 2022)
12-56273166-C-T		not specified	Uncertain significance (May 17, 2023)
12-56273235-A-C		not specified	Uncertain significance (Nov 17, 2022)
12-56273696-A-G		not specified	Uncertain significance (Jun 29, 2023)
12-56274778-C-T		not specified	Uncertain significance (Jan 17, 2024)
12-56274826-G-A		not specified	Uncertain significance (Jan 03, 2024)
12-56276015-G-A			Benign (Aug 08, 2018)
12-56276131-C-T		not specified	Uncertain significance (Nov 14, 2023)
12-56282430-T-G		not specified	Uncertain significance (Mar 23, 2023)
12-56282436-C-T		not specified	Uncertain significance (Dec 13, 2021)
12-56282481-T-C		not specified	Uncertain significance (Nov 21, 2023)
12-56282971-A-G			Benign (Apr 04, 2018)
12-56282985-G-A		not specified	Uncertain significance (Oct 05, 2023)
12-56283844-A-G		not specified	Uncertain significance (Mar 05, 2024)
12-56283855-C-T		not specified	Uncertain significance (Dec 13, 2023)
12-56285933-G-C		not specified	Uncertain significance (Nov 10, 2022)
12-56285943-C-T			Likely benign (Mar 29, 2018)
12-56300180-C-A		not specified	Uncertain significance (Jan 03, 2024)
12-56300197-G-C		not specified	Uncertain significance (Mar 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CS	protein_coding	protein_coding	ENST00000351328	11	28694

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.984	0.0160	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.33	107	257	0.416	0.0000132	3004
Missense in Polyphen		20	93.233	0.21452		1104
Synonymous	2.66	65	98.6	0.659	0.00000505	947
Loss of Function	4.42	4	30.2	0.132	0.00000209	287

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000680	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Warburg Effect;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Amino Acid metabolism;TCA Cycle;Citrate cycle;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of proteins;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;Lysine degradation;TCA cycle;TCA cycle;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.805

Intolerance Scores

• loftool: 0.0494
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.682
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cs
• Phenotype: hearing/vestibular/ear phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: carbohydrate metabolic process;tricarboxylic acid cycle
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;extracellular exosome
• Molecular function: RNA binding;citrate (Si)-synthase activity