MNAT1
protein-codingMNAT1 component of CDK activating kinase, the group of Nucleotide excision repair|CDK activating kinase complex|Ring finger proteins
Gene summary
The protein encoded by this gene, along with cyclin H and CDK7, forms the CDK-activating kinase (CAK) enzymatic complex. This complex activates several cyclin-associated kinases and can also associate with TFIIH to activate transcription by RNA polymerase II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~235.2 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 MNAT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002431.4. 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 | 1 | 1 | ||||
| missense | 32 | 1 | 33 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 32 | 1 | 1 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002422.1 | 8 | MANE Select | |
| Ensembl | ENSP00000261245.4 | 8 | MANE Select | |
| RefSeq | NP_001171434.1 | 7 | Standard | |
| Ensembl | ENSP00000446437.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nucleotide excision repair - Homo sapiens (human)
- Basal transcription factors - Homo sapiens (human)
- Eukaryotic Transcription Initiation
- G1 to S cell cycle control
- DNA Repair
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- G1/S transition of mitotic cell cycle
- DNA repair
- transcription-coupled nucleotide-excision repair
- nucleotide-excision repair, preincision complex assembly
Molecular Function
- protein binding
- DNA-dependent ATPase activity
- zinc ion binding
- RNA polymerase II CTD heptapeptide repeat kinase activity
- protein N-terminus binding
Cellular Component
- nucleoplasm
- transcription factor TFIIH holo complex
- cytosol
- cyclin-dependent protein kinase activating kinase holoenzyme complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261245
- Coding exons
- 8
- Length
- 235212
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125748
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.718 | 123 | 148 | 0.834 | 0.00000650 | 2026 |
| Missense (PolyPhen) | 46 | 52.692 | 0.87301 | 772 | ||
| Synonymous | 0.473 | 48 | 52.4 | 0.917 | 0.00000237 | 538 |
| Loss of Function | -0.105 | 18 | 17.5 | 1.03 | 8.92e-7 | 230 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00025 | rare |
| Latino/Admixed American | 0.000093 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00037 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. {ECO:0000269|PubMed:10024882}.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.866
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |