PKMYT1
protein-codingprotein kinase, membrane associated tyrosine/threonine 1, the group of Protein phosphatase 1 regulatory subunits
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PKMYT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004203.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 109 | 2 | 111 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 116 | 2 | 1 | 119 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004194.3 | 8 | MANE Select | |
| Ensembl | ENSP00000262300.8 | 8 | MANE Select | |
| RefSeq | NP_001245379.1 | 8 | Standard | |
| RefSeq | NP_001245380.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Oocyte meiosis - Homo sapiens (human)
- Progesterone-mediated oocyte maturation - Homo sapiens (human)
- Cell Cycle
- G2/M DNA replication checkpoint
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- G2/M transition of mitotic cell cycle
- mitotic cell cycle
- protein phosphorylation
- regulation of mitotic nuclear division
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- kinase activity
Cellular Component
- Golgi membrane
- nucleus
- nucleoplasm
- nucleolus
- endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262300
- Coding exons
- 8
- Length
- 12516
- Individuals with no LoFs
- 125236
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125248
- p
- 0.0000479
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0740 | 286 | 290 | 0.988 | 0.0000187 | 3104 |
| Missense (PolyPhen) | 49 | 68.258 | 0.71786 | 785 | ||
| Synonymous | -0.625 | 134 | 125 | 1.07 | 0.00000760 | 1097 |
| Loss of Function | 3.13 | 5 | 20.2 | 0.248 | 9.66e-7 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00019 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000070 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development. {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:9001210}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.532
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.51
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |