THG1L

Chr 5AR

tRNA-histidine guanylyltransferase 1 like

THG1L encodes a mitochondrial guanyltransferase that adds GMP to the 5' end of tRNA(His) for proper protein synthesis and functions as a guanyl-nucleotide exchange factor regulating mitochondrial fusion dynamics. Mutations cause spinocerebellar ataxia, autosomal recessive 28, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (LOEUF 1.03), suggesting that complete loss of function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.031 OMIM phenotype
Clinical SummaryTHG1L
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Gene-Disease Validity (ClinGen)
spinocerebellar ataxia, autosomal recessive 28 · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.48
OE 0.59 (0.351.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.03Z-score
OE missense 0.99 (0.881.13)
169 obs / 170.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.351.03)
00.351.4
Missense OE0.99 (0.881.13)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 9 / 15.2Missense obs/exp: 169 / 170.0Syn Z: -0.59
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTHG1L-related cerebellar ataxiaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6549th %ile
GOF
0.5465th %ile
LOF
0.3260th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

THG1L · 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

No active trials found for this gene.

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Clinical Literature
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