NKX3-1

Chr 8

NK3 homeobox 1

Also known as: BAPX2, NKX3, NKX3.1, NKX3A

NCBI Gene: 4824ENSG00000167034UniProt: Q99801

This homeobox transcription factor regulates prostate epithelial cell proliferation and duct formation during normal prostate development. Mutations in NKX3-1 are primarily associated with prostate cancer susceptibility rather than pediatric neurological conditions. The gene shows low constraint against loss-of-function variants, reflecting its tissue-specific role in prostate biology.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
1.38
LOEUF
—
Mechanism
Clinical Summary— NKX3-1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 41 VUS of 131 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.000
Z-score 0.80
OE 0.70 (0.38–1.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.92–1.22)
133 obs / 126.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.38–1.38)
0≤0.351.4
Missense OE1.06 (0.92–1.22)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 6 / 8.5Missense obs/exp: 133 / 126.0Syn Z: 0.02

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS41
Likely Benign2
Benign2
78
Pathogenic
4
Likely Pathogenic
41
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
38
3
0
41
Likely Benign
0
1
1
0
2
Benign
0
0
0
2
2
Total039862127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NKX3-1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Association Aamong Ppolymorphisms in the Aapoptosis-Rrelated NKX3-1, Caspase-3, Caspase-9, and BCL-2 Genes and Prostate Cancer Susceptibility From 9706 Cases and 12,567 Controls.
Feng Y et al.·Cancer Rep (Hoboken)
2025Open AccessCohort
Prostatic lineage differentiation from human embryonic stem cells through inducible expression of NKX3-1.
Wang S et al.·Stem Cell Res Ther
2024Open Access
Fibroblast-derived exosomal microRNA regulates NKX3-1 expression in androgen-sensitive, androgen receptor-dependent prostate cancer cells.
Matsuda C et al.·J Cell Biochem
2023
Polymorphic variants of the CASP3, CASP9, BCL-2 and NKX3-1 genes as candidate markers for prostate cancer susceptibility and poor prognosis.
de Souza MR et al.·Mol Biol Rep
2022
KLF5-induced miR-487a augments the progression of osteosarcoma cells by targeting NKX3-1 in vitro.
Luo A et al.·Oncol Lett
2022Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients