NKX2-2
Chr 20NK2 homeobox 2
Also known as: NKX2.2, NKX2B
NKX2-2 encodes a homeobox transcription factor that regulates development of insulin-producing beta cells in the pancreas and is involved in central nervous system morphogenesis and axonal guidance. Mutations cause permanent neonatal diabetes mellitus with neurological features, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.665), reflecting its critical role in early pancreatic and neurological development.
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 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
82 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 | 21 | 0 | 21 |
Likely Pathogenic | 1 | 0 | 3 | 0 | 4 |
VUS | 0 | 10 | 6 | 1 | 17 |
Likely Benign | 0 | 3 | 2 | 25 | 30 |
Benign | 0 | 3 | 3 | 1 | 7 |
| Total | 1 | 16 | 35 | 27 | 79 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NKX2-2 · 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