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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NKX1-2
NK1 homeobox 2
Chromosome 10 · 10q26.13
NCBI Gene: 390010Ensembl: ENSG00000229544.9HGNC: HGNC:31652UniProt: Q9UD57
7PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificregulation of transcription by RNA polymerase IIcell differentiationglomerulonephritisopen-angle glaucomaAbnormality of the skeletal systemB-cell acute lymphoblastic leukemia
✦AI Summary

NKX1-2 is a transcriptional regulator that functions as a master controller of multiple developmental processes. In pre-implantation embryo development, NKX1-2 serves as a Wnt-dependent master regulator essential for proper embryogenesis, controlling ribosome biogenesis, RNA translation, and nucleolus structure 1. Loss of NKX1-2 function leads to chromosome 10, reduced blastomere numbers, and impaired blastocoel formation, ultimately causing developmental arrest 1. The protein plays a crucial role in cell fate determination, promoting adipogenesis in mesenchymal stem cells while inhibiting osteoblast differentiation by suppressing the antiadipogenic factor NR2F2 2. NKX1-2 expression is induced during 3T3-L1 adipocyte differentiation, and its knockdown almost completely blocks this process 2. In liver regeneration, NKX1-2 is downstream of lncHand2 and triggers c-Met signaling pathway activation 3. The gene also marks neuromesodermal progenitor cells and is involved in human primordial germ cell-like cell specification 45. Additionally, NKX1-2 shows expression in the central nervous system during development and its methylation status can be influenced by environmental temperature 67.

Sources cited
1
NKX1-2 is a Wnt-dependent master regulator controlling pre-implantation development, ribosome biogenesis, and nucleolus structure
PMID: 38701778
2
NKX1-2 promotes adipogenesis while inhibiting osteoblast differentiation by suppressing NR2F2
PMID: 31615896
3
NKX1-2 triggers c-Met signaling in liver regeneration downstream of lncHand2
PMID: 29653123
4
NKX1-2 is required for identifying primordial germ cell-like cell progenitors
PMID: 39710672
5
NKX1-2 marks neuromesodermal progenitor cells in human development
PMID: 29899136
6
NKX1-2 shows expression patterns in central nervous system development
PMID: 15183316
7
NKX1-2 methylation status can be affected by environmental temperature
PMID: 31884209
Disease Associationsⓘ20
glomerulonephritisOpen Targets
0.13Weak
open-angle glaucomaOpen Targets
0.12Weak
Abnormality of the skeletal systemOpen Targets
0.10Suggestive
B-cell acute lymphoblastic leukemiaOpen Targets
0.10Suggestive
osteoarthritis, hipOpen Targets
0.09Suggestive
cervical carcinomaOpen Targets
0.08Suggestive
liver diseaseOpen Targets
0.07Suggestive
brain astrocytomaOpen Targets
0.07Suggestive
AnisometropiaOpen Targets
0.07Suggestive
total hip arthroplastyOpen Targets
0.07Suggestive
CholecystitisOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.06Suggestive
diabetes mellitusOpen Targets
0.06Suggestive
spina bifidaOpen Targets
0.06Suggestive
chondromalaciaOpen Targets
0.06Suggestive
oropharynx cancerOpen Targets
0.05Suggestive
dementiaOpen Targets
0.04Suggestive
corneal ulcerOpen Targets
0.04Suggestive
placenta praeviaOpen Targets
0.04Suggestive
osteoarthritis, kneeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ANXA13Shared pathway100%ELF1Shared pathway100%ELF2Shared pathway100%ELF5Shared pathway100%ELK3Shared pathway100%ELK4Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
13%
Heart
0%
Ovary
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
NKX1-2ANXA13ELF1ELF2ELF5ELK3ELK4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UD57
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.89LoF Tolerant
pLIⓘ
0.66Intermediate
Observed/Expected LoF0.19 [0.07–0.89]
RankingsWhere NKX1-2 stands among ~20K protein-coding genes
  • #17,881of 20,598
    Most Researched7
  • #8,048of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedNKX1-2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The transcription factor NKX1-2 promotes adipogenesis and may contribute to a balance between adipocyte and osteoblast differentiation.
PMID: 31615896
J Biol Chem · 2019
1.00
2
Expression of sax1/nkx1.2 and sax2/nkx1.1 in zebrafish.
PMID: 15183316
Gene Expr Patterns · 2004
0.90
3
The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.
PMID: 38701778
Stem Cell Reports · 2024
0.80
4
Environmental temperature and human epigenetic modifications: A systematic review.
PMID: 31884209
Environ Pollut · 2020
0.70
5
Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling.
PMID: 29653123
J Hepatol · 2018
0.60