PCMT1

Chr 6

protein-L-isoaspartate (D-aspartate) O-methyltransferase

Also known as: PIMT

NCBI Gene: 5110ENSG00000120265UniProt: P22061

This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

49
ClinVar variants
19
Pathogenic / LP
0.78
pLI score
0
Active trials
Clinical Summary— PCMT1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 29 VUS of 49 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.785
Z-score 2.95
OE 0.14 (0.06–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.90Z-score
OE missense 0.58 (0.48–0.69)
91 obs / 158.1 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.0.14 (0.06–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.48–0.69)
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.1.00
0≤1.21.6
LoF obs/exp: 2 / 13.8Missense obs/exp: 91 / 158.1Syn Z: -0.02

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS29
Likely Benign1
19
Pathogenic
29
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
25
4
0
29
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total02523149

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

View in ClinVar →

Protein Context — Lollipop Plot

PCMT1 · 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
PCMT1 regulates the migration, invasion, and apoptosis of prostate cancer through modulating the PI3K/AKT/GSK-3β pathway.
Zhong J et al.·Aging (Albany NY)
2023
PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer.
Dong L et al.·IUBMB Life
2018
PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer.
Liu J et al.·Eur J Med Res
2023
[Prognostic Value of PCMT1 Expression in Gastric Cancer and Its Regulatory Effect on Spindle Assembly Checkpoints].
Wang Y et al.·Sichuan Da Xue Xue Bao Yi Xue Ban
2023
Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus.
Yang ML et al.·Autoimmunity
2023
Proteomic Signatures and Blood Adenosine Triphosphate Levels as Markers of Empagliflozin Efficacy in Type 2 Diabetes Mellitus and Heart Failure.
Omurzakova U et al.·Horm Metab Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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