IMPACT
Chr 18impact RWD domain protein
Also known as: RWDD5
IMPACT encodes a translational regulator that maintains protein synthesis during cellular stress conditions by inhibiting the GCN2 kinase pathway and is required for proper neuronal differentiation and neurite outgrowth. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically manifesting in early childhood. This gene is highly intolerant to loss-of-function variants, primarily affecting the central nervous system.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
72 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 17 | 6 | 0 | 23 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 17 | 40 | 0 | 57 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IMPACT · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Timing and Resistance Exercise: Impact on Eating and Metabolism
NOT YET RECRUITINGA Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer
RECRUITINGNANOVAE to Treat Knee Osteoarthritis (KOA)
NOT YET RECRUITINGProbiotic Impact on Cognitive Performance, and Metabolic Outcomes in Overweight Young Adults With Impaired Glucose Regulation
RECRUITINGIntravesical Gentamicin to Prevent Recurrent UTI
RECRUITINGInspire HER: Inspiring the Heart and Emotions for Radical Health
RECRUITINGHCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy
ACTIVE NOT RECRUITINGThe GENPET Study - An Imaging Study of FCH-PET-CT in Men With Prostate Cancer and a DNA Repair Gene Mutation.
RECRUITINGInfusion of Alloreactive nk Cells for Mrd-positive Aml Patients
RECRUITINGGPR146 and Cholesterol Metabolism
NOT YET RECRUITINGGenetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response
ACTIVE NOT RECRUITINGA 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.
RECRUITINGExternal Resources
Links to major genomics databases and tools