LCMT1

Chr 16

leucine carboxyl methyltransferase 1

Also known as: CGI-68, LCMT, PPMT1

LCMT1 encodes a methyltransferase that methylates the C-terminal leucine residue of protein phosphatase 2A catalytic subunits, which is critical for proper phosphatase regulation. Mutations cause autosomal recessive intellectual disability with variable neurological features including seizures and developmental delay. This gene shows low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.87
Clinical SummaryLCMT1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.01
OE 0.53 (0.330.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.63Z-score
OE missense 0.87 (0.760.99)
160 obs / 184.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.330.87)
00.351.4
Missense OE0.87 (0.760.99)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 11 / 20.9Missense obs/exp: 160 / 184.0Syn Z: -0.06
DN
0.7035th %ile
GOF
0.4974th %ile
LOF
0.2191th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LCMT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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