THUMPD3
Chr 3THUMP domain 3 tRNA guanosine methyltransferase
The THUMPD3 protein is the catalytic subunit of a methyltransferase complex that methylates guanosine nucleotides at specific positions in tRNAs, essential for proper tRNA modification and function. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, representing a neurodevelopmental disorder affecting brain growth and cognitive development. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that biallelic mutations are likely required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
161 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 | 50 | 0 | 50 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 72 | 12 | 0 | 84 |
Likely Benign | 0 | 2 | 1 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 74 | 68 | 0 | 142 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
THUMPD3 · 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