ATAT1
protein-codingalpha tubulin acetyltransferase 1, the group of Lysine acetyltransferases
Gene summary
This gene encodes a protein that localizes to clathrin-coated pits, where it acetylates alpha tubulin on lysine 40. This process may be important in microtubule growth, for instance during chemotaxis and the formation of cilium. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
- C6orf134
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.0 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 ATAT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001413067.1. 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 | 2 | ||||
| missense | 30 | 4 | 34 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 34 | 4 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001399996.1 | 13 | MANE Select | |
| Ensembl | ENSP00000365668.4 | 13 | MANE Select | |
| RefSeq | NP_001026892.1 | 13 | Standard | |
| RefSeq | NP_001177653.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| atat1 | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in lymphocytes - TarBase
- Cilium Assembly
- Organelle biogenesis and maintenance
Biological Process
- spermatogenesis
- dentate gyrus development
- regulation of fat cell differentiation
- neuron development
- cilium assembly
Molecular Function
- lysine N-acetyltransferase activity, acting on acetyl phosphate as donor
- tubulin N-acetyltransferase activity
- coenzyme binding
Cellular Component
- Golgi apparatus
- cytosol
- microtubule
- clathrin-coated pit
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330083
- Coding exons
- 13
- Length
- 19982
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 47
- Defined
- 125748
- p
- 0.000187
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.38 | 180 | 240 | 0.750 | 0.0000142 | 2596 |
| Missense (PolyPhen) | 57 | 82.947 | 0.68719 | 868 | ||
| Synonymous | 1.15 | 69 | 82.3 | 0.839 | 0.00000412 | 829 |
| Loss of Function | 2.34 | 16 | 29.8 | 0.537 | 0.00000206 | 268 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0012 | notable |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00022 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly. {ECO:0000255|HAMAP-Rule:MF_03130, ECO:0000269|PubMed:20829795, ECO:0000269|PubMed:21068373, ECO:0000269|PubMed:24097348, ECO:0000269|PubMed:24906155}.;
Intolerance Scores
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |