TBL1X
Chr XX-linkedtransducin beta like 1 X-linked
Also known as: CHNG8, EBI, SMAP55, TBL1
The protein functions as an F-box-like protein that recruits the ubiquitin/proteasome complex to nuclear receptor-regulated transcription units and plays an essential role in transcription activation by mediating degradation of repressor complexes. Mutations cause X-linked congenital nongoitrous hypothyroidism. This gene is highly constrained against loss-of-function variants, indicating that such variants are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
311 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 | 84 | 0 | 84 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 1 | 77 | 13 | 0 | 91 |
Likely Benign | 0 | 2 | 1 | 6 | 9 |
Benign | 0 | 1 | 12 | 3 | 16 |
Conflicting | — | 1 | |||
| Total | 2 | 80 | 111 | 9 | 203 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TBL1X · 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