CSKMT

Chr 11

citrate synthase lysine methyltransferase

Also known as: CS-KMT, METTL12, U99HG

NCBI Gene: 751071 ENSG00000214756 UniProt: A8MUP2

The protein functions as a mitochondrial protein-lysine methyltransferase that selectively trimethylates citrate synthase, introducing methyl groups in a distributive manner. Mutations in this gene have not been definitively associated with human disease based on the provided information. The gene shows tolerance to loss-of-function variants with low constraint scores.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.002

Z-score 0.91

OE 0.65 (0.34–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.02Z-score

OE missense 1.25 (1.10–1.42)

169 obs / 135.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.34–1.35)

0≤0.351.4

Missense OE?1.25 (1.10–1.42)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 5 / 7.7Missense obs/exp: 169 / 135.5Syn Z: -0.82

Background carrier burden — how many people carry a rare variant somewhere in CSKMT?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

348 rare PASS variants

Rare truncating (LoF)

1 in 690

89 rare PASS variants

Rare synonymous (reference)

1 in 250

152 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CSKMT. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 1,100
South Asian	~43k	1 in 140	1 in 350
Remaining (unassigned)	~30k	1 in 130	1 in 560
European (Finnish)	~27k	1 in 480	1 in 4,500
Admixed American	~22k	1 in 190	1 in 360
African / African American	~21k	1 in 130	1 in 960
East Asian	~20k	1 in 180	1 in 2,500
Ashkenazi Jewish	~13k	1 in 1,300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓