LETM1
Chr 4ARleucine zipper and EF-hand containing transmembrane protein 1
Also known as: CONDMIM, KHE, Mdm38, SLC55A1
The LETM1 protein localizes to the inner mitochondrial membrane where it maintains mitochondrial tubular morphology and mediates calcium and potassium/proton transport across the membrane. Mutations cause childhood-onset neurodegeneration with multisystem involvement due to mitochondrial dysfunction, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (pLI near 1, LOEUF 0.738), indicating that complete loss of function is likely incompatible with survival.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
508 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 | 1 | 5 | 140 | 0 | 146 |
Likely Pathogenic | 2 | 1 | 10 | 0 | 13 |
VUS | 5 | 144 | 21 | 3 | 173 |
Likely Benign | 0 | 10 | 39 | 86 | 135 |
Benign | 0 | 11 | 6 | 8 | 25 |
Conflicting | — | 3 | |||
| Total | 8 | 171 | 216 | 97 | 495 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LETM1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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