FASTKD3
protein-codingFAST kinase domains 3, the group of FASTK mitochondrial RNA binding family
Gene summary
This gene encodes a member of a small family of Fas-activated serine/threonine kinase domain (FASTKD) containing proteins that share an amino terminal mitochondrial targeting domain and multiple carboxy terminal FAST domains as well as a putative RNA-binding RAP domain. The members of this family are ubiquitously expressed and are generally most abundant in mitochondria-enriched tissues such as heart, skeletal muscle and brown-adipose tissue. Some members of this protein family may play a role in apoptosis. The protein encoded by this gene interacts with components of the mitochondrial respiratory and translation networks. A pseudogene of this gene is also present on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.9 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 FASTKD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024091.4. 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 | 1 | 3 | ||
| missense | 67 | 12 | 1 | 80 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 71 | 13 | 2 | 86 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076996.2 | 6 | MANE Select | |
| Ensembl | ENSP00000264669.5 | 6 | MANE Select | |
| Ensembl | ENSP00000426008.1 | 1 | Standard | |
| Ensembl | ENSP00000421798.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- mitochondrial respiratory chain complex IV assembly
- regulation of mitochondrial mRNA stability
- cellular respiration
- positive regulation of mitochondrial translation
Molecular Function
- RNA binding
- protein kinase activity
- protein binding
Cellular Component
- nucleus
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264669
- Coding exons
- 6
- Length
- 9879
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 122
- Defined
- 125747
- p
- 0.000485
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.814 | 296 | 338 | 0.875 | 0.0000171 | 4323 |
| Missense (PolyPhen) | 68 | 83.074 | 0.81855 | 1138 | ||
| Synonymous | -0.119 | 134 | 132 | 1.01 | 0.00000679 | 1289 |
| Loss of Function | 1.01 | 17 | 22.1 | 0.769 | 0.00000110 | 320 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00093 | 0.00092 | rare |
| Latino/Admixed American | 0.00065 | 0.00064 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00062 | 0.00057 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for normal mitochondrial respiration (PubMed:20869947). Increases steady-state levels and half-lives of a subset of mature mitochondrial mRNAs MT-ND2, MT-ND3, MT-CYTB, MT-CO2, and MT-ATP8/6. Promotes MT-CO1 mRNA translation and increases mitochondrial complex IV assembly and activity (PubMed:27789713). {ECO:0000269|PubMed:20869947, ECO:0000269|PubMed:27789713}.;
Recessive Scores
- pRec
- 0.0618
Intolerance Scores
- LoFtool
- 0.903
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.140
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |