IMPACT
protein-codingimpact RWD domain protein
Gene summary
Predicted to enable protein sequestering activity. Predicted to be involved in several processes, including GCN2-mediated signaling; cellular response to amino acid starvation; and regulation of gene expression. Predicted to act upstream of or within negative regulation of protein phosphorylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.9 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 IMPACT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018439.4. 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 | 19 | 19 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 26 | 0 | 0 | 26 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060909.2 | 11 | MANE Select | |
| Ensembl | ENSP00000284202.4 | 11 | MANE Select | |
| Ensembl | ENSP00000464363.1 | 7 | Standard | |
| Ensembl | ENSP00000463710.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- negative regulation of protein phosphorylation
- biological_process
- negative regulation of protein complex assembly
- negative regulation of protein autophosphorylation
Molecular Function
- molecular_function
- actin binding
- ribosome binding
Cellular Component
- cellular_component
- cytoplasm
- polysome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284202
- Coding exons
- 11
- Length
- 26920
- Individuals with no LoFs
- 125674
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 72
- Defined
- 125746
- p
- 0.000286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.169 | 165 | 171 | 0.964 | 0.00000890 | 2123 |
| Missense (PolyPhen) | 57 | 58.268 | 0.97824 | 693 | ||
| Synonymous | -0.641 | 63 | 56.9 | 1.11 | 0.00000316 | 545 |
| Loss of Function | 1.15 | 14 | 19.5 | 0.718 | 9.09e-7 | 256 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00022 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0016 | 0.0015 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00042 | 0.00039 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Plays a role as a negative regulator of the EIF2AK4/GCN2 kinase activity; impairs GCN1- mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. May be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, plays a role in differentiation of neuronal cells by stimulating neurite outgrowth. {ECO:0000250|UniProtKB:O55091}.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- LoFtool
- 0.758
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.283
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |