PASK
protein-codingPAS domain containing serine/threonine kinase, the group of PAS domain containing
Gene summary
This gene encodes a member of the serine/threonine kinase family that contains two PAS domains. Expression of this gene is regulated by glucose, and the encoded protein plays a role in the regulation of insulin gene expression. Downregulation of this gene may play a role in type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.2 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 PASK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015148.4. 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 | 5 | 8 | 8 | 21 | ||
| missense | 214 | 26 | 8 | 248 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 226 | 34 | 16 | 276 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055963.2 | 17 | MANE Select | |
| Ensembl | ENSP00000234040.5 | 17 | MANE Select | |
| RefSeq | NP_001239048.1 | 17 | Standard | |
| RefSeq | NP_001239049.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- intracellular signal transduction
- regulation of respiratory gaseous exchange
- negative regulation of glycogen biosynthetic process
- positive regulation of translation
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- phosphatidylinositol binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358649
- Coding exons
- 17
- Length
- 44166
- Individuals with no LoFs
- 124965
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 781
- Defined
- 125748
- p
- 0.00312
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0430 | 772 | 769 | 1.00 | 0.0000493 | 8602 |
| Missense (PolyPhen) | 244 | 273.35 | 0.89262 | 3245 | ||
| Synonymous | -0.480 | 353 | 342 | 1.03 | 0.0000251 | 2785 |
| Loss of Function | 1.76 | 40 | 53.9 | 0.741 | 0.00000289 | 618 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0016 | 0.0016 | notable |
| Latino/Admixed American | 0.0023 | 0.0023 | notable |
| Ashkenazi Jewish | 0.0013 | 0.0013 | notable |
| East Asian | 0.0019 | 0.0017 | notable |
| Finnish | 0.0027 | 0.0027 | notable |
| European (Non-Finnish) | 0.0045 | 0.0044 | notable |
| South Asian | 0.0017 | 0.0017 | notable |
| Other | 0.0034 | 0.0034 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate to respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.833
- RVIS EVS
- 0.32
- RVIS percentile EVS
- 72.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.761
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |