PKMYT1

Chr 16

protein kinase, membrane associated tyrosine/threonine 1

Also known as: MYT1, PPP1R126

The protein encoded by this gene is a membrane-associated serine/threonine kinase that negatively regulates cell cycle progression by phosphorylating and inactivating cyclin-dependent kinase 1, thereby controlling the transition from G2 phase to mitosis. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy with severe seizures and developmental delays. The gene shows moderate tolerance to loss-of-function variants, and the associated disorder primarily affects the central nervous system with prominent neurodevelopmental features.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.52
Clinical SummaryPKMYT1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.219
Z-score 3.13
OE 0.25 (0.130.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.07Z-score
OE missense 0.99 (0.901.09)
286 obs / 289.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.130.52)
00.351.4
Missense OE0.99 (0.901.09)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 20.2Missense obs/exp: 286 / 289.5Syn Z: -0.62
DN
0.6551th %ile
GOF
0.6737th %ile
LOF
0.4037th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

PKMYT1 · 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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