CSKMT

protein-coding

citrate synthase lysine methyltransferase, the group of Small nucleolar RNA protein coding host genes|7BS protein lysine methyltransferases

Gene summary

Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine dimethylation; peptidyl-lysine monomethylation; and peptidyl-lysine trimethylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

METTL12

MANE transcript

NM_001043229.2

Inheritance

—

ClinVar variants

U:45B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr11:62,665,309-62,668,496

External References & Databases

Ensembl (ENSG00000214756)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 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 CSKMT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001043229.2. 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						0
missense			44 clinvar			44
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	45	0	1	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001043229.2	RefSeq	NP_001036694.1	2	MANE Select
ENST00000532971.2	Ensembl	ENSP00000431287.1	2	MANE Select
ENST00000913097.1	Ensembl	ENSP00000583156.1	2	Standard
ENST00000913097.2	Ensembl	ENSP00000583156.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein methylation
peptidyl-lysine trimethylation
peptidyl-lysine monomethylation
peptidyl-lysine dimethylation

Molecular Function

lysine N-methyltransferase activity
protein-lysine N-methyltransferase activity

Cellular Component

mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000532971
Coding exons: 2
Length: 3188
Individuals with no LoFs: 124040
Homozygous LoFs: 14
Heterozygous LoFs: 741
Defined: 124795
p: 0.00303

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.02	169	136	1.25	0.00000682	1516
Missense (PolyPhen)		54	45.735	1.1807		551
Synonymous	-0.817	69	60.9	1.13	0.00000322	547
Loss of Function	0.907	5	7.72	0.648	5.01e-7	65

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0010	0.0010	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.0042	0.0040	notable
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.019	0.019	notable
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein-lysine methyltransferase that selectively trimethylates citrate synthase (CS) in mitochondria (PubMed:28391595, PubMed:28887308). Seems to conduct trimethylation in a highly distributive manner rather than in a processive manner, and thus introduces a single methly group per binding event (PubMed:28887308). {ECO:0000269|PubMed:28391595, ECO:0000269|PubMed:28887308}.;

Intolerance Scores

RVIS EVS: 0.71
RVIS percentile EVS: 85.53

Essentials

Essential (gene trap): N