TKTL2
Chr 4transketolase like 2
TKTL2 encodes a protein with transketolase activity that plays an essential role in total cellular transketolase activity and cell proliferation. Mutations cause autosomal recessive intellectual disability with seizures and macrocephaly. The gene is not highly constrained against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
142 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 | 39 | 0 | 39 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 89 | 6 | 0 | 95 |
Likely Benign | 0 | 5 | 0 | 2 | 7 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 94 | 46 | 2 | 142 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TKTL2 · 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