GADD45A
protein-codinggrowth arrest and DNA damage inducible alpha
Gene summary
This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Dec 2010]
- DDIT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.1 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 GADD45A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001924.4. 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 | ||||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 13 | 0 | 1 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001915.1 | 4 | MANE Select | |
| Ensembl | ENSP00000360025.4 | 4 | MANE Select | |
| RefSeq | NP_001186670.1 | 3 | Standard | |
| RefSeq | NP_001186671.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Non-small cell lung cancer - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Melanoma - Homo sapiens (human)
- Cell cycle - Homo sapiens (human)
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- activation of MAPKKK activity
- DNA repair
- negative regulation of protein kinase activity
- apoptotic process
Molecular Function
- RNA polymerase II core promoter sequence-specific DNA binding
- protein binding
- kinase binding
- protein homodimerization activity
- protein heterodimerization activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370986
- Coding exons
- 4
- Length
- 3278
- Individuals with no LoFs
- 125554
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125558
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.41 | 60 | 99.5 | 0.603 | 0.00000478 | 1076 |
| Missense (PolyPhen) | 15 | 47.084 | 0.31858 | 494 | ||
| Synonymous | -1.31 | 54 | 43.0 | 1.25 | 0.00000200 | 328 |
| Loss of Function | 1.36 | 3 | 6.84 | 0.439 | 2.91e-7 | 81 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0.000099 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.838
Intolerance Scores
- LoFtool
- 0.341
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |