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    MLXIP MLX interacting protein [ Homo sapiens (human) ]

    Gene ID: 22877, updated on 27-Nov-2024

    Summary

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    Official Symbol
    MLXIPprovided by HGNC
    Official Full Name
    MLX interacting proteinprovided by HGNC
    Primary source
    HGNC:HGNC:17055
    See related
    Ensembl:ENSG00000175727 MIM:608090; AllianceGenome:HGNC:17055
    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
    MIR; MONDOA; bHLHe36
    Summary
    This gene encodes a protein that functions as part of a heterodimer to activate transcription. The encoded protein forms a heterodimer with Max-like protein X (MLX) and is involved in the regulation of genes in response to cellular glucose levels. [provided by RefSeq, Mar 2014]
    Expression
    Ubiquitous expression in colon (RPKM 27.3), ovary (RPKM 19.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MLXIP in Genome Data Viewer
    Location:
    12q24.31
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (122078756..122147344)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (122074570..122143121)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (122516662..122631891)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5004 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122460343-122461158 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5006 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7196 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7197 Neighboring gene BAF chromatin remodeling complex subunit BCL7A Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122492684-122493298 Neighboring gene Sharpr-MPRA regulatory region 9922 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7198 Neighboring gene Sharpr-MPRA regulatory region 8907 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7199 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122509410-122510254 Neighboring gene long intergenic non-protein coding RNA 2985 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7200 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5008 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7201 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7202 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7203 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122580754-122581254 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122581255-122581755 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:122582507-122583160 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122583161-122583814 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7205 Neighboring gene Sharpr-MPRA regulatory region 11163 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122611084-122611596 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:122611597-122612107 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:122614034-122615233 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122622713-122623575 Neighboring gene MPRA-validated peak2016 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:122651061-122651663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5010 Neighboring gene leucine rich repeat containing 43 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7209 Neighboring gene interleukin 31 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5011 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4 Neighboring gene diablo IAP-binding mitochondrial protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival. Wernicke CM, et al. Leuk Res, 2012 Sep. PMID 22748921
    2. MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress. Sipol A, et al. Blood, 2022 Feb 24. PMID 33908607, Free PMC Article
    3. Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity. Kaadige MR, et al. Proc Natl Acad Sci U S A, 2009 Sep 1. PMID 19706488, Free PMC Article
    4. Cellular acidosis triggers human MondoA transcriptional activity by driving mitochondrial ATP production. Wilde BR, et al. Elife, 2019 Feb 5. PMID 30717828, Free PMC Article
    5. Genetic polymorphisms of LMX1B and MLXIP are associated with hip osteoarthritis in the Chinese population. Chen C, et al. Biomark Med, 2024 Aug 17. PMID 39263770,

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic polymorphisms of LMX1B and MLXIP are associated with hip osteoarthritis in the Chinese population.
      Title: Genetic polymorphisms of LMX1B and MLXIP are associated with hip osteoarthritis in the Chinese population.
    2. MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress.
      Title: MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress.
    3. MondoA-Thioredoxin-Interacting Protein Axis Maintains Regulatory T-Cell Identity and Function in Colorectal Cancer Microenvironment.
      Title: MondoA-Thioredoxin-Interacting Protein Axis Maintains Regulatory T-Cell Identity and Function in Colorectal Cancer Microenvironment.
    4. TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion.
      Title: TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion.
    5. MondoA drives muscle lipid accumulation and insulin resistance.
      Title: MondoA drives muscle lipid accumulation and insulin resistance.
    6. In response to acidosis, MondoA shows preferential binding to just two targets, TXNIP and its paralog ARRDC4. Because these transcriptional targets are suppressors of glucose uptake, the authors propose that MondoA is critical for restoring metabolic homeostasis in response to high energy charge.
      Title: Cellular acidosis triggers human MondoA transcriptional activity by driving mitochondrial ATP production.
    7. Data (including data from studies in knockout mice) suggest that MONDOA shuttles to nucleus of pancreatic beta-cells where it is required for induction of glucose-responsive genes arrestin domain-containing protein 4 (ARRDC4) and thioredoxin interacting protein (TXNIP).
      Title: MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.
    8. MondoA-directed programs have a key role in the coordinated control of myocyte lipid balance and insulin signaling
      Title: MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling.
    9. Evaluation of the conservation of ChREBP and MondoA sequences demonstrate that MondoA is better conserved and potentially mediates more ancient function in glucose metabolism.
      Title: Contrasting Patterns in the Evolution of Vertebrate MLX Interacting Protein (MLXIP) and MLX Interacting Protein-Like (MLXIPL) Genes.
    10. These results suggest that C771G polymorphism of MLXIPL gene is associated with coronary stenosis and its severity.
      Title: C771G (His241Gln) polymorphism of MLXIPL gene, TG levels and coronary artery disease: a case control study.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
    EBI GWAS Catalog
    Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.
    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

    • KIAA0867

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    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 RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein dimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II 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 mitochondrial outer membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    MLX-interacting protein
    Names
    Mlx interactor
    class E basic helix-loop-helix protein 36
    transcriptional activator MondoA

    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_033995.1 RefSeqGene

      Range
      5029..73617
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_014938.6 → NP_055753.3  MLX-interacting protein

      See identical proteins and their annotated locations for NP_055753.3

      Status: REVIEWED

      Source sequence(s)
      AF245480, AW996647, BC151841, BE207198, BM007462, BM558759, BM857835, BQ218664, BQ445885, CA426212
      Consensus CDS
      CCDS73540.1
      UniProtKB/Swiss-Prot
      A7MBN0, O94945, Q7LC47, Q8IXP1, Q8TAH9, Q8WVQ0, Q8WYA5, Q9HAP2
      Related
      ENSP00000312834.6, ENST00000319080.12
      Conserved Domains (1) summary
      cd00083
      Location:718 → 773
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      122078756..122147344
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006719290.5 → XP_006719353.1  MLX-interacting protein isoform X1

      Conserved Domains (1) summary
      cd00083
      Location:718 → 774
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

    2. XM_006719292.5 → XP_006719355.1  MLX-interacting protein isoform X3

      Conserved Domains (1) summary
      cd00083
      Location:718 → 774
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

    3. XM_006719291.5 → XP_006719354.1  MLX-interacting protein isoform X2

      Conserved Domains (1) summary
      cd00083
      Location:718 → 773
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

    4. XM_047428537.1 → XP_047284493.1  MLX-interacting protein isoform X4

    5. XM_047428538.1 → XP_047284494.1  MLX-interacting protein isoform X6

    6. XM_006719293.4 → XP_006719356.1  MLX-interacting protein isoform X5

      Conserved Domains (1) summary
      PHA03247
      Location:339 → 568
      PHA03247; large tegument protein UL36; Provisional

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_011332697.1 Reference GRCh38.p14 PATCHES

      Range
      21022..86533
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      122074570..122143121
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371448.1 → XP_054227423.1  MLX-interacting protein isoform X1

    2. XM_054371450.1 → XP_054227425.1  MLX-interacting protein isoform X3

    3. XM_054371449.1 → XP_054227424.1  MLX-interacting protein isoform X2

    4. XM_054371451.1 → XP_054227426.1  MLX-interacting protein isoform X4

    5. XM_054371453.1 → XP_054227428.1  MLX-interacting protein isoform X6

    6. XM_054371452.1 → XP_054227427.1  MLX-interacting protein isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HAP2.2 GenPept UniProtKB/Swiss-Prot:Q9HAP2

    Gene LinkOut

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

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