CS

protein-coding

citrate synthase

Gene summary

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]

MANE transcript

NM_004077.3

Inheritance

—

ClinVar variants

U:36B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr12:56,271,699-56,300,391

External References & Databases

Ensembl (ENSG00000062485)

Transcript & Mutation Effects

hg38 • Region Span ~28.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004077.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	2 clinvar	3
missense			35 clinvar	1 clinvar		36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	36	2	2	40

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004077.3	RefSeq	NP_004068.2	11	MANE Select
ENST00000351328.8	Ensembl	ENSP00000342056.3	11	MANE Select
ENST00000542324.6	Ensembl	ENSP00000440543.2	11	Standard
ENST00000546891.5	Ensembl	ENSP00000446492.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

carbohydrate metabolic process
tricarboxylic acid cycle

Molecular Function

RNA binding
citrate (Si)-synthase activity

Cellular Component

nucleus
mitochondrion
mitochondrial matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000351328
Coding exons: 11
Length: 28694
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.33	107	257	0.416	0.0000132	3004
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.805

Intolerance Scores

LoFtool: 0.0494
RVIS EVS: -0.03
RVIS percentile EVS: 51.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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