LCMT1

Chr 16

leucine carboxyl methyltransferase 1

Also known as: CGI-68, LCMT, PPMT1

NCBI Gene: 51451ENSG00000205629UniProt: Q9UIC8

LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal leucine residue (leu309) of the catalytic subunit of protein phosphatase-2A (PPP2CA; MIM 176915) (De Baere et al., 1999 [PubMed 10600115]).[supplied by OMIM, Mar 2008]

102
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LCMT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 51 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.87LOEUF
pLI 0.000
Z-score 2.01
OE 0.53 (0.33–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.87 (0.76–0.99)
160 obs / 184.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.33–0.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.76–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 11 / 20.9Missense obs/exp: 160 / 184.0Syn Z: -0.06

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS51
Likely Benign2
Benign1
27
Pathogenic
3
Likely Pathogenic
51
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
48
3
0
51
Likely Benign
0
2
0
0
2
Benign
0
0
1
0
1
Total05034084

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Construction and validation of a prognostic model for colorectal cancer based on migrasome-related long non-coding RNAs.
Lv Q et al.·PeerJ
2025Functional
White spot syndrome virus hijacks host PP2A-FOXO axes to promote its propagation.
Li C et al.·Int J Biol Macromol
2024
Identification and validation of a tyrosine metabolism-related prognostic prediction model and characterization of the tumor microenvironment infiltration in hepatocellular carcinoma.
Zhou Y et al.·Front Immunol
2022Functional
Leucine Carboxyl Methyltransferase 1 Overexpression Protects Against Cognitive and Electrophysiological Impairments in Tg2576 APP Transgenic Mice.
Gnanaprakash M et al.·J Alzheimers Dis
2021
NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.
Palanichamy K et al.·Clin Cancer Res
2017
Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation.
Meng L et al.·Front Immunol
2021
PP2A methylesterase, PME-1, and PP2A methyltransferase, LCMT-1, control sensitivity to impairments caused by injury-related oligomeric tau.
Sundaresh SN et al.·Alzheimers Dement
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
Rasool RU et al.·Nat Commun
2023🔓 Open Access
Low-dose benzo[a]pyrene exposure induces hepatic lipid deposition through LCMT1/PP2Ac-mediated autophagy inhibition.
Li Y et al.·Food Chem Toxicol
2023
Hepatic leucine carboxyl methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism.
Mo J et al.·J Nutr Biochem
2023
HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia.
Lei L et al.·Int J Mol Sci
2022🔓 Open Access
LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma.
Zhang N et al.·Transl Oncol
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools