In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target genes Iype et al. (2004) [PubMed 15056733].[supplied by OMIM, Mar 2008] See more...

Aliases for NKX6-1 Gene

Aliases for NKX6-1 Gene

  • NK6 Homeobox 1 2 3 5
  • Homeobox Protein NK-6 Homolog A 3 4
  • Homeobox Protein Nkx-6.1 3 4
  • NKX6A 3 4
  • NK6 Transcription Factor Related, Locus 1 (Drosophila) 2
  • NK6 Transcription Factor Related, Locus 1 3
  • NK Homeobox (Drosophila), Family 6, A 2
  • NK6 Transcription Factor Homolog A 3
  • NK Homeo Box, Family 6, Member A 3
  • NK Homeobox, Family 6, A 3
  • NKX6.1 3
  • NKX6-1 5
  • Nkx6.1 2

External Ids for NKX6-1 Gene

Previous HGNC Symbols for NKX6-1 Gene

  • NKX6A

Previous GeneCards Identifiers for NKX6-1 Gene

  • GC04M085339
  • GC04M085708
  • GC04M085807
  • GC04M085872
  • GC04M085771
  • GC04M081156
  • GC04M085413

Summaries for NKX6-1 Gene

Entrez Gene Summary for NKX6-1 Gene

  • In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target genes Iype et al. (2004) [PubMed 15056733].[supplied by OMIM, Mar 2008]

GeneCards Summary for NKX6-1 Gene

NKX6-1 (NK6 Homeobox 1) is a Protein Coding gene. Diseases associated with NKX6-1 include Maturity-Onset Diabetes Of The Young and Pancreatic Agenesis. Among its related pathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Regulation of beta-cell development. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is NKX6-2.

UniProtKB/Swiss-Prot Summary for NKX6-1 Gene

  • Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Involved in the development of insulin-producing beta cells in the islets of Langerhans at the secondary transition (By similarity). Together with NKX2-2 and IRX3 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals (By similarity).

Gene Wiki entry for NKX6-1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NKX6-1 Gene

Genomics for NKX6-1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NKX6-1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J084498 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 257.1 +0.9 891 3.2 ZIC2 ZBTB10 FEZF1 ZNF341 SIN3A ZNF513 KLF9 SP2 BCL11B ZBTB48 NKX6-1 HSALNG0035608 lnc-NKX6-1-3 lnc-NKX6-1-4 GPAT3
GH04J084581 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 9.3 -84.8 -84817 5.6 ZNF600 ATF2 ZNF10 JUND POLR2A ZBTB10 YY1 ZNF217 REST FEZF1 CDS1 lnc-NKX6-1-5 NKX6-1 WDFY3-AS2 FJ601684-347 WDFY3
GH04J084530 Enhancer 0.8 Ensembl ENCODE 11 -32.0 -31997 1.8 FEZF1 CTBP1 PRDM6 TCF7L2 ZBTB40 PKNOX1 DPF2 NCOA3 SP7 OSR2 CDS1 NKX6-1 WDFY3-AS2 HSALNG0035613 piR-30188-131 LOC102723338 lnc-NKX6-1-5
GH04J083640 Enhancer 0.9 Ensembl ENCODE 9.8 +859.3 859274 0.6 ZNF654 ZNF592 CEBPA YY1 CTCF CEBPB REST TRIM22 ARNT NFATC3 ABRAXAS1 GPAT3 HELQ NKX6-1 RF00017-3915 HSALNG0035595-001 HSALNG0035595-002
GH04J083644 Enhancer 0.7 Ensembl 9.8 +854.4 854360 0.5 ZNF654 ATF2 CEBPA ATF3 CTCF REST CEBPB TRIM22 RAD21 IRF4 ABRAXAS1 GPAT3 NKX6-1 RF00017-3915 HSALNG0035595-001 HSALNG0035595-002
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NKX6-1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NKX6-1

Top Transcription factor binding sites by QIAGEN in the NKX6-1 gene promoter:
  • AREB6
  • GR
  • GR-alpha
  • GR-beta
  • POU2F1
  • POU2F1a
  • POU6F1 (c2)
  • Sp1
  • TBP
  • YY1

Genomic Locations for NKX6-1 Gene

Latest Assembly
chr4:84,491,985-84,499,292
(GRCh38/hg38)
Size:
7,308 bases
Orientation:
Minus strand

Previous Assembly
chr4:85,413,138-85,420,445
(GRCh37/hg19 by Entrez Gene)
Size:
7,308 bases
Orientation:
Minus strand

chr4:85,413,140-85,419,603
(GRCh37/hg19 by Ensembl)
Size:
6,464 bases
Orientation:
Minus strand

Genomic View for NKX6-1 Gene

Genes around NKX6-1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NKX6-1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NKX6-1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NKX6-1 Gene

Proteins for NKX6-1 Gene

  • Protein details for NKX6-1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P78426-NKX61_HUMAN
    Recommended name:
    Homeobox protein Nkx-6.1
    Protein Accession:
    P78426

    Protein attributes for NKX6-1 Gene

    Size:
    367 amino acids
    Molecular mass:
    37849 Da
    Quaternary structure:
    No Data Available

neXtProt entry for NKX6-1 Gene

Post-translational modifications for NKX6-1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NKX6-1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NKX6-1 Gene

Domains & Families for NKX6-1 Gene

Gene Families for NKX6-1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NKX6-1 Gene

InterPro:
Blocks:
  • Lambda and other repressor helix-turn-helix signature

Suggested Antigen Peptide Sequences for NKX6-1 Gene

GenScript: Design optimal peptide antigens:
  • Homeobox protein NK-6 homolog A (NKX61_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P78426

UniProtKB/Swiss-Prot:

NKX61_HUMAN :
  • The C-terminal domain contributes to sequence-specific DNA-binding.
Domain:
  • The C-terminal domain contributes to sequence-specific DNA-binding.
genes like me logo Genes that share domains with NKX6-1: view

Function for NKX6-1 Gene

Molecular function for NKX6-1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Involved in the development of insulin-producing beta cells in the islets of Langerhans at the secondary transition (By similarity). Together with NKX2-2 and IRX3 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals (By similarity).

Phenotypes From GWAS Catalog for NKX6-1 Gene

Gene Ontology (GO) - Molecular Function for NKX6-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA,IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IEA --
GO:0003677 DNA binding IEA --
GO:0003682 chromatin binding IEA --
genes like me logo Genes that share ontologies with NKX6-1: view
genes like me logo Genes that share phenotypes with NKX6-1: view

Animal Models for NKX6-1 Gene

MGI Knock Outs for NKX6-1:

Transcription Factor Targets for NKX6-1 Gene

Selected GeneGlobe predicted Target genes for NKX6-1
Targeted motifs for NKX6-1 Gene
HOMER Transcription Factor Regulatory Elements motif NKX6-1
  • Consensus sequence: GKTAATGR Submotif: canonical Cell Type: Islet GEO ID: GSE40975

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NKX6-1

No data available for Enzyme Numbers (IUBMB) and Human Phenotype Ontology for NKX6-1 Gene

Localization for NKX6-1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NKX6-1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NKX6-1 gene
Compartment Confidence
nucleus 5
extracellular 4
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NKX6-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IBA 21873635
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with NKX6-1: view

Pathways & Interactions for NKX6-1 Gene

genes like me logo Genes that share pathways with NKX6-1: view

Pathways by source for NKX6-1 Gene

SIGNOR curated interactions for NKX6-1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for NKX6-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA,ISS --
GO:0001764 neuron migration IEA --
GO:0003309 type B pancreatic cell differentiation IEA --
GO:0003323 type B pancreatic cell development IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with NKX6-1: view

Drugs & Compounds for NKX6-1 Gene

No Compound Related Data Available

Transcripts for NKX6-1 Gene

mRNA/cDNA for NKX6-1 Gene

1 REFSEQ mRNAs :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NKX6-1

Alternative Splicing Database (ASD) splice patterns (SP) for NKX6-1 Gene

No ASD Table

Relevant External Links for NKX6-1 Gene

GeneLoc Exon Structure for
NKX6-1

Expression for NKX6-1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NKX6-1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NKX6-1 Gene

This gene is overexpressed in Esophagus - Muscularis (x23.9) and Esophagus - Gastroesophageal Junction (x21.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NKX6-1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NKX6-1

SOURCE GeneReport for Unigene cluster for NKX6-1 Gene:

Hs.546270

mRNA Expression by UniProt/SwissProt for NKX6-1 Gene:

P78426-NKX61_HUMAN
Tissue specificity: Pancreatic beta cells.

Evidence on tissue expression from TISSUES for NKX6-1 Gene

  • Pancreas(4.8)
  • Nervous system(2.8)
  • Stomach(2.6)
  • Intestine(2.4)
  • Heart(2.4)
  • Liver(2.3)
  • Muscle(2.3)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with NKX6-1: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NKX6-1 Gene

Orthologs for NKX6-1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for NKX6-1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NKX6-1 29 30
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NKX6-1 29 30
  • 91.23 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NKX6-1 30
  • 91 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia NKX6-1 29 30
  • 90.14 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nkx6-1 29
  • 89.56 (n)
Mouse
(Mus musculus)
Mammalia Nkx6-1 29 16 30
  • 89.01 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NKX6-1 30
  • 81 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NKX6-1 30
  • 94 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nkx6-1 29
  • 72.78 (n)
Zebrafish
(Danio rerio)
Actinopterygii nkx6.1 29 30
  • 70.68 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta HGTX 30
  • 30 (a)
OneToMany
Barley
(Hordeum vulgare)
Liliopsida Hv.1836 29
Wheat
(Triticum aestivum)
Liliopsida Ta.2891 29
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 34 (a)
OneToMany
Species where no ortholog for NKX6-1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Worm (Caenorhabditis elegans)

Evolution for NKX6-1 Gene

ENSEMBL:
Gene Tree for NKX6-1 (if available)
TreeFam:
Gene Tree for NKX6-1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NKX6-1: view image
Alliance of Genome Resources:
Additional Orthologs for NKX6-1

Paralogs for NKX6-1 Gene

(9) SIMAP similar genes for NKX6-1 Gene using alignment to 2 proteins:

  • NKX61_HUMAN
  • F8VWZ9_HUMAN
genes like me logo Genes that share paralogs with NKX6-1: view

Variants for NKX6-1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NKX6-1 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs147737825 Benign: not provided 84,493,490(-) C/T
NM_006168.2(NKX6-1):c.903G>A (p.Thr301=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NKX6-1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NKX6-1 Gene

Variant ID Type Subtype PubMed ID
nsv829998 CNV gain 17160897

Variation tolerance for NKX6-1 Gene

Gene Damage Index Score: 1.55; 30.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NKX6-1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NKX6-1
Leiden Open Variation Database (LOVD)
NKX6-1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NKX6-1 Gene

Disorders for NKX6-1 Gene

MalaCards: The human disease database

(7) MalaCards diseases for NKX6-1 Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NKX6-1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NKX6-1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NKX6-1 Gene

Publications for NKX6-1 Gene

  1. Isolation, characterization, and chromosomal mapping of the human Nkx6.1 gene (NKX6A), a new pancreatic islet homeobox gene. (PMID: 9119408) Inoue H … Permutt MA (Genomics 1997) 2 3 4 22
  2. Distinct regulation of hepatic nuclear factor 1alpha by NKX6.1 in pancreatic beta cells. (PMID: 20106981) Donelan W … Yang LJ (The Journal of biological chemistry 2010) 3 22
  3. Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects. (PMID: 16873704) Yokoi N … Seino S (Diabetes 2006) 3 40
  4. Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding. (PMID: 32457219) Tran DT … Itkin-Ansari P (Diabetes 2020) 3
  5. NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer. (PMID: 32707737) Chung HH … Shih YL (International journal of molecular sciences 2020) 3

Products for NKX6-1 Gene

Sources for NKX6-1 Gene