PRKX
protein-codingprotein kinase cAMP-dependent X-linked catalytic subunit, the group of AGC family kinases
Gene summary
This gene encodes a serine threonine protein kinase that has similarity to the catalytic subunit of cyclic AMP dependent protein kinases. The encoded protein is developmentally regulated and may be involved in renal epithelial morphogenesis. This protein may also be involved in macrophage and granulocyte maturation. Abnormal recombination between this gene and a related pseudogene on chromosome Y is a frequent cause of sex reversal disorder in XX males and XY females. Pseudogenes of this gene are found on chromosomes X, 15 and Y. [provided by RefSeq, Feb 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~109.3 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 PRKX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005044.5. 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 | 4 | 3 | 1 | 8 | ||
| missense | 59 | 3 | 62 | |||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 71 | 6 | 1 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005035.1 | 8 | MANE Select | |
| Ensembl | ENSP00000262848.5 | 8 | MANE Select | |
| Ensembl | ENSP00000580455.1 | 7 | Standard | |
| Ensembl | ENSP00000580455.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chemokine signaling pathway
- EGFR1
Biological Process
- angiogenesis
- endothelial cell proliferation
- cell adhesion
- peptidyl-serine phosphorylation
- myeloid cell differentiation
Molecular Function
- cAMP-dependent protein kinase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262848
- Coding exons
- 8
- Length
- 109239
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 4
- Defined
- 125745
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.60 | 93 | 148 | 0.630 | 0.0000132 | 2362 |
| Missense (PolyPhen) | 26 | 51.943 | 0.50055 | 888 | ||
| Synonymous | -1.10 | 78 | 66.6 | 1.17 | 0.00000670 | 673 |
| Loss of Function | 1.80 | 4 | 10.2 | 0.391 | 7.18e-7 | 195 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00013 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000037 | 0.000026 | rare |
| South Asian | 0.000053 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation. {ECO:0000269|PubMed:12082174, ECO:0000269|PubMed:16236808, ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:17980165, ECO:0000269|PubMed:19367327, ECO:0000269|PubMed:21684272, ECO:0000269|PubMed:9860982}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving PRKX is a cause of sex reversal disorder. Translocation t(X;Y)(p22;p11) with PRKY. Chromosomal translocations proximal to PRKY account for about 30% of the cases of sex reversal disorder in XX males and XY females.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.388
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.966
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |