NAT8
protein-codingN-acetyltransferase 8 (putative), the group of GCN5 related N-acetyltransferases
Gene summary
This gene, isolated using the differential display method to detect tissue-specific genes, is specifically expressed in kidney and liver. The encoded protein shows amino acid sequence similarity to N-acetyltransferases. A similar protein in Xenopus affects cell adhesion and gastrulation movements, and may be localized in the secretory pathway. A highly similar paralog is found in a cluster with this gene. [provided by RefSeq, Sep 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.7 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 NAT8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003960.4. 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 | 0 | |||||
| missense | 48 | 8 | 2 | 58 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 49 | 8 | 2 | 59 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003951.3 | 1 | MANE Select | |
| Ensembl | ENSP00000272425.3 | 1 | MANE Select | |
| Ensembl | ENSP00000522444.1 | 1 | Standard | |
| Ensembl | ENSP00000522444.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione metabolism - Homo sapiens (human)
- Metapathway biotransformation Phase I and II
- Metabolism of proteins
- Amyloid fiber formation
Biological Process
- glutathione metabolic process
- positive regulation of gene expression
- peptidyl-lysine N6-acetylation
- response to drug
- negative regulation of apoptotic process
Molecular Function
- lysine N-acetyltransferase activity, acting on acetyl phosphate as donor
- protein binding
- cysteine-S-conjugate N-acetyltransferase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- endoplasmic reticulum-Golgi intermediate compartment
- integral component of membrane
- endoplasmic reticulum-Golgi intermediate compartment membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000272425
- Coding exons
- 1
- Length
- 1562
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.57 | 186 | 135 | 1.38 | 0.00000799 | 1465 |
| Missense (PolyPhen) | 33 | 24.051 | 1.3721 | 310 | ||
| Synonymous | -1.69 | 70 | 54.2 | 1.29 | 0.00000292 | 483 |
| Loss of Function |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acetylates the free alpha-amino group of cysteine S- conjugates to form mercapturic acids (PubMed:20392701). This is the final step in a major route for detoxification of a wide variety of reactive electrophiles which starts with their incorporation into glutathione S-conjugates. The glutathione S- conjugates are then further processed into cysteine S-conjugates and finally mercapturic acids which are water soluble and can be readily excreted in urine or bile. Alternatively, may have a lysine N-acetyltransferase activity catalyzing peptidyl-lysine N6- acetylation of various proteins. Thereby, may regulate apoptosis through the acetylation and the regulation of the expression of PROM1 (PubMed:24556617). May also regulate amyloid beta-peptide secretion through acetylation of BACE1 and the regulation of its expression in neurons (PubMed:19011241). {ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:20392701, ECO:0000269|PubMed:24556617}.;
Recessive Scores
- pRec
- 0.742
Intolerance Scores
- LoFtool
- 0.633
- RVIS EVS
- 0.86
- RVIS percentile EVS
- 88.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.206
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |