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    PAX4 paired box 4 [ Homo sapiens (human) ]

    Gene ID: 5078, updated on 27-Dec-2024

    Summary

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    Official Symbol
    PAX4provided by HGNC
    Official Full Name
    paired box 4provided by HGNC
    Primary source
    HGNC:HGNC:8618
    See related
    Ensembl:ENSG00000106331 MIM:167413; AllianceGenome:HGNC:8618
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KPD; MODY9
    Summary
    This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See PAX4 in Genome Data Viewer
    Location:
    7q32.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (127610292..127618142, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (128921978..128929835, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (127250346..127258196, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375489 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:127249495-127249995 Neighboring gene PAX4 5' regulatory region Neighboring gene fascin actin-bundling protein 3 Neighboring gene ARF GTPase 5 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:127291844-127292462 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26588 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr7:127305706-127306528 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26589 Neighboring gene SND1 divergent transcript Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:127343327-127343826 Neighboring gene staphylococcal nuclease and tudor domain containing 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:127366923-127367714 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:127375481-127375695 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:127438882-127439229 Neighboring gene CD2 cytoplasmic tail binding protein 2 pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. PAX4 has the potential to function as a tumor suppressor in human melanoma. Hata S, et al. Int J Oncol, 2008 Nov. PMID 18949370
    2. Overexpression of PAX4 reduces glucagon expression in differentiating hESCs. Gage BK, et al. Islets, 2014. PMID 25483960, Free PMC Article
    3. Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients. Chen M, et al. Pharmacogenomics J, 2014 Oct. PMID 24752311
    4. Defective PAX4 R192H transcriptional repressor activities associated with maturity onset diabetes of the young and early onset-age of type 2 diabetes. Kooptiwut S, et al. J Diabetes Complications, 2012 Jul-Aug. PMID 22521316
    5. Expression of dominant negative form of PAX4 in human insulinoma. Miyamoto T, et al. Biochem Biophys Res Commun, 2001 Mar 23. PMID 11263967

    See all (75) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.
      Title: PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.
    2. Pax4 in Health and Diabetes.
      Title: Pax4 in Health and Diabetes.
    3. Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.
      Title: Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.
    4. Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY.
      Title: Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY.
    5. Transcription factor PAX4 facilitates gastric cancer progression through interacting with miR-27b-3p/Grb2 axis.
      Title: Transcription factor PAX4 facilitates gastric cancer progression through interacting with miR-27b-3p/Grb2 axis.
    6. [Alternative Variants of Pax4 Human Transcription Factor: Comparative Transcriptional Activity].
      Title: [Alternative Variants of Pax4 Human Transcription Factor: Comparative Transcriptional Activity].
    7. genetic association studies in population in Republic of Korea: Data suggest that SNPs in PAX4 and GLP1R are associated with type 2 diabetes (T2D) in the population studied. In genome-wide associations, PAX4 Arg192His increased risk of T2D; GLP1R Arg131Gln decreased risk of T2D. (PAX4 = paired box 4 protein; GLP1R = glucagon-like peptide 1 receptor)
      Title: Nonsynonymous Variants in PAX4 and GLP1R Are Associated With Type 2 Diabetes in an East Asian Population.
    8. The rs10229583 polymorphism near PAX4 is associated with gestational diabetes mellitus in Chinese women.
      Title: The rs10229583 polymorphism near paired box gene 4 is associated with gestational diabetes mellitus in Chinese women.
    9. Study identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes.
      Title: Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.
    10. Viability of beta-cell was reduced under glucotoxic stress condition for the cells overexpressing either PAX4 R192H or PAX4 P321H or both. Thus these PAX4 polymorphisms may increase T2D risk by defective transcription regulation of target genes and/or decreased beta-cell survival in high glucose condition.
      Title: PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects.
    Submit: New GeneRIF Correction See all GeneRIFs (43)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Diabetes mellitus, ketosis-prone
    MedGen: C3837958 OMIM: 612227 GeneReviews: Not available
    		not available
    Maturity-onset diabetes of the young type 9
    MedGen: C2677132 OMIM: 612225 GeneReviews: Maturity-Onset Diabetes of the Young Overview
    		not available
    Type 2 diabetes mellitus
    MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC129960

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in animal organ morphogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in brain development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in forebrain development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in retina development in camera-type eye IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sensory organ development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in type B pancreatic cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    paired box protein Pax-4
    Names
    paired box gene 4
    paired domain gene 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012848.1 RefSeqGene

      Range
      2585..10435
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001366110.1 → NP_001353039.1  paired box protein Pax-4 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC073934
      Consensus CDS
      CCDS94191.1
      UniProtKB/TrEMBL
      A0A1W2PPX4, A4D0Z1
      Related
      ENSP00000491782.1, ENST00000639438.3
      Conserved Domains (2) summary
      smart00351
      Location:5 → 129
      PAX; Paired Box domain
      pfam00046
      Location:174 → 226
      Homeobox; Homeobox domain

    2. NM_001366111.1 → NP_001353040.1  paired box protein Pax-4 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AB008913, AC073934
      Consensus CDS
      CCDS94190.1
      UniProtKB/Swiss-Prot
      O43316, O95161, Q6B0H0
      UniProtKB/TrEMBL
      J3KPG0
      Related
      ENSP00000368014.4, ENST00000378740.6
      Conserved Domains (2) summary
      smart00351
      Location:5 → 129
      PAX; Paired Box domain
      pfam00046
      Location:174 → 226
      Homeobox; Homeobox domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      127610292..127618142 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      128921978..128929835 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_006193.2: Suppressed sequence

      Description
      NM_006193.2: This RefSeq has been removed because currently there is insufficient support for the transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43316.1 GenPept UniProtKB/Swiss-Prot:O43316

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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