TMLHE

Chr XXLR

trimethyllysine hydroxylase, epsilon

Also known as: AUTSX6, BBOX2, TMLD, TMLH, TMLHED, XAP130

NCBI Gene: 55217ENSG00000185973UniProt: Q9NVH6OMIM: 300777

Trimethyllysine dioxygenase catalyzes the first step of carnitine biosynthesis by converting trimethyllysine to hydroxytrimethyllysine, enabling fatty acid transport across the inner mitochondrial membrane. X-linked recessive mutations cause autism susceptibility. The gene is highly intolerant to loss-of-function variants (pLI 0.9999), indicating critical functional importance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
XLRLOEUF 1.181 OMIM phenotype
Clinical Summary— TMLHE
🧬
Gene-Disease Validity (ClinGen)
autism spectrum disorder · XLDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 1.13
OE 0.65 (0.38–1.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.64Z-score
OE missense 0.84 (0.72–0.99)
112 obs / 132.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.38–1.18)
0≤0.351.4
Missense OE0.84 (0.72–0.99)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 8 / 12.3Missense obs/exp: 112 / 132.7Syn Z: -0.35

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TMLHE · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
X-Linked Autism Type 9 Caused by a Hemizygote Pathogenic Variant in the TMLHE Gene: Etiological Diagnosis in an Adult Male with Moderate Intellectual Disability.
Verhoeven WMA et al.·Int Med Case Rep J
2025Open Access
Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels.
Liepinsh E et al.·Mol Autism
2023Open Access
Low cardiac content of long-chain acylcarnitines in TMLHE knockout mice prevents ischaemia-reperfusion-induced mitochondrial and cardiac damage.
Liepinsh E et al.·Free Radic Biol Med
2021
Complex recombination with deletion in the F8 and duplication in the TMLHE mediated by int22h copies during early embryogenesis.
Chen C et al.·Thromb Haemost
2017
Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation.
Ziats MN et al.·Am J Med Genet A
2015
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients