ENOPH1
Chr 4enolase-phosphatase 1
Also known as: E1, MASA, MST145, mtnC
ENOPH1 encodes a bifunctional enzyme that catalyzes key steps in the methionine salvage pathway, converting methylthioadenosine-derived intermediates to regenerate methionine. Biallelic mutations cause a rare autosomal recessive disorder characterized by intellectual disability, developmental delay, and seizures with onset in infancy or early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.82), suggesting some tolerance to haploinsufficiency while homozygous loss causes significant neurological impairment.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
61 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 | 34 | 0 | 34 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 10 | 4 | 0 | 14 |
Likely Benign | 0 | 1 | 1 | 1 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 11 | 43 | 1 | 55 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ENOPH1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools