NKX1-1
Chr 4NK1 homeobox 1
Also known as: HSPX153, NKX-1.1, SAX2
The protein is a transcription factor that regulates genes involved in energy homeostasis, with expression predominantly in the brainstem near serotonergic neurons. Mutations cause a severe neurodevelopmental disorder characterized by early-onset failure to thrive, lack of subcutaneous fat, and early lethality, following an autosomal recessive inheritance pattern. The gene shows moderate constraint against loss-of-function variants (pLI 0.71, LOEUF 0.72).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
161 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 138 |
Likely Pathogenic | — | — | — | — | 6 |
VUS | — | — | — | — | 14 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 2 |
| Total | — | 161 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NKX1-1 · 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 →No open access results found
External Resources
Links to major genomics databases and tools