PKMYT1

Chr 16

protein kinase, membrane associated tyrosine/threonine 1

Also known as: MYT1, PPP1R126

NCBI Gene: 9088ENSG00000127564UniProt: Q99640

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein is a membrane-associated kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating cyclin-dependent kinase 1. The activity of the encoded protein is regulated by polo-like kinase 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

172
ClinVar variants
35
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— PKMYT1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 116 VUS of 172 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.
0.52LOEUF
pLI 0.219
Z-score 3.13
OE 0.25 (0.13–0.52)
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.
0.07Z-score
OE missense 0.99 (0.90–1.09)
286 obs / 289.5 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.0.25 (0.13–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.09)
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.1.07
0≤1.21.6
LoF obs/exp: 5 / 20.2Missense obs/exp: 286 / 289.5Syn Z: -0.62

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
VUS116
Likely Benign2
Benign1
35
Pathogenic
116
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
103
13
0
116
Likely Benign
0
2
0
0
2
Benign
0
0
0
1
1
Total0105481154

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

View in ClinVar →

Protein Context — Lollipop Plot

PKMYT1 · 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
Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification.
Hu Y et al.·Mol Cancer
2022
PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.
Liu B et al.·Signal Transduct Target Ther
2025
A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.
Ghelli Luserna di Rorà A et al.·J Hematol Oncol
2020Review
Synthetic lethality of mRNA quality control complexes in cancer.
Prindle V et al.·Nature
2025
LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.
He Y et al.·Mol Cancer
2021
Meisoindigo Acts as a Molecular Glue to Target PKMYT1 for Degradation in Chronic Myeloid Leukemia Therapy.
Zhang ZX et al.·Adv Sci (Weinh)
2025
Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.
Szychowski J et al.·J Med Chem
2022
Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR.
Xu H et al.·Nat Commun
2025
Targeting Protein Kinase, Membrane-Associated Tyrosine/Threonine 1 (PKMYT1) for Precision Cancer Therapy: From Discovery to Clinical Trial.
Yang M et al.·J Med Chem
2024Review
Low-Molecular Weight Cyclin E Confers a Vulnerability to PKMYT1 Inhibition in Triple-Negative Breast Cancer.
Li M et al.·Cancer Res
2024
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