Brain-lung-thyroid syndrome: genes and variants
Brain-lung-thyroid syndrome is linked to 1 analyzed protein (NKX2-1). 14 DNA variants are known to cause it; 11 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Brain-lung-thyroid syndrome
NKX2-1: Homeobox protein Nkx-2.1
It controls developmental and tissue-specific gene programs in lung, thyroid, and basal ganglia. Haploinsufficiency causes brain-lung-thyroid syndrome, variably combining chorea or developmental movement disorder, neonatal respiratory disease, and thyroid dysfunction.
14 disease-causing and 11 uncertain variants in NKX2-1 are linked to Brain-lung-thyroid syndrome.
Where Brain-lung-thyroid syndrome variants cluster
- NKX2-1 Homeobox (positions 161–220): 13 of 14 disease-causing changes, 5.7× more than its size predicts.
Known disease-causing variants in Brain-lung-thyroid syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NKX2-1 R213C | 213 | Homeobox | Disease-causing (★★) |
| NKX2-1 P202L | 202 | Homeobox | Disease-causing (★★) |
| NKX2-1 W208L | 208 | Homeobox | Disease-causing (★★) |
| NKX2-1 L176Q | 176 | Homeobox | Disease-causing (★★) |
| NKX2-1 R179P | 179 | Homeobox | Disease-causing (★★) |
| NKX2-1 P261R | 261 | Disease-causing (★★) | |
| NKX2-1 R161L | 161 | Homeobox | Disease-causing (★★) |
| NKX2-1 V205A | 205 | Homeobox | Disease-causing (★) |
| NKX2-1 R213P | 213 | Homeobox | Disease-causing (★) |
| NKX2-1 H212D | 212 | Homeobox | Disease-causing (★) |
| NKX2-1 Q204L | 204 | Homeobox | Disease-causing (★) |
| NKX2-1 I207M | 207 | Homeobox | Disease-causing (★) |
| NKX2-1 Q172L | 172 | Homeobox | Disease-causing (★) |
| NKX2-1 V205F | 205 | Homeobox | Disease-causing |
Same protein, different disease
- Benign hereditary chorea is also caused by NKX2-1 variants; they fall partly in the same places as the Brain-lung-thyroid syndrome variants (4 disease-causing).
Diseases related to Brain-lung-thyroid syndrome
- Multiple myeloma, also linked to NKX2-1
- Thyroid cancer, nonmedullary, 2, also linked to NKX2-1
- Benign hereditary chorea, also linked to NKX2-1
- Hereditary ataxia, also linked to NKX2-1
Frequently asked questions
Which genes are linked to Brain-lung-thyroid syndrome?
In CATVariant, Brain-lung-thyroid syndrome is linked to 1 analyzed protein: NKX2-1 (Homeobox protein Nkx-2.1).
How many genetic variants are linked to Brain-lung-thyroid syndrome?
52 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 11 are of uncertain significance or have conflicting reports.
Which uncertain variants in Brain-lung-thyroid syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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