TIGAR
Chr 12TP53 induced glycolysis regulatory phosphatase
Also known as: C12orf5, FR2BP
The TIGAR protein functions as a fructose-bisphosphatase that blocks glycolysis and redirects glucose metabolism into the pentose phosphate pathway, reducing cellular reactive oxygen species and protecting against oxidative stress. Mutations in TIGAR cause autosomal recessive primary microcephaly with simplified gyral pattern, a neurodevelopmental disorder affecting brain growth and cortical folding. The gene shows moderate constraint against loss-of-function variants, suggesting intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
100 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 | 54 | 0 | 54 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 20 | 7 | 0 | 27 |
Likely Benign | 0 | 3 | 1 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 23 | 67 | 0 | 90 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TIGAR · 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