Details for: MLXIPL

Gene ID: 51085

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MLXIPL

Ensembl ID: ENSG00000009950

Description: MLX interacting protein like

Cell Significance Landscape

Associated with

  • Ampk inhibits chrebp transcriptional activation activity
    (R-HSA-163680)
  • Chrebp activates metabolic gene expression
    (R-HSA-163765)
  • Integration of energy metabolism
    (R-HSA-163685)
  • Metabolism
    (R-HSA-1430728)
  • Pka-mediated phosphorylation of key metabolic factors
    (R-HSA-163358)
  • Pp2a-mediated dephosphorylation of key metabolic factors
    (R-HSA-163767)
  • Anatomical structure morphogenesis
    (GO:0009653)
  • Carbohydrate response element binding
    (GO:0035538)
  • Chromatin
    (GO:0000785)
  • Cytoplasm
    (GO:0005737)
  • Cytosol
    (GO:0005829)
  • Dna-binding transcription activator activity
    (GO:0001216)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription factor binding
    (GO:0140297)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Dna binding
    (GO:0003677)
  • Energy homeostasis
    (GO:0097009)
  • Fatty acid homeostasis
    (GO:0055089)
  • Glucose homeostasis
    (GO:0042593)
  • Glucose mediated signaling pathway
    (GO:0010255)
  • Lipid biosynthetic process
    (GO:0008610)
  • Negative regulation of dna-templated transcription
    (GO:0045892)
  • Negative regulation of oxidative phosphorylation
    (GO:0090324)
  • Negative regulation of peptidyl-serine phosphorylation
    (GO:0033137)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleoplasm
    (GO:0005654)
  • Nucleus
    (GO:0005634)
  • Positive regulation of cell population proliferation
    (GO:0008284)
  • Positive regulation of dna-templated transcription
    (GO:0045893)
  • Positive regulation of fatty acid biosynthetic process
    (GO:0045723)
  • Positive regulation of glycolytic process
    (GO:0045821)
  • Positive regulation of lipid biosynthetic process
    (GO:0046889)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Positive regulation of transcription from rna polymerase ii promoter by glucose
    (GO:0000432)
  • Protein heterodimerization activity
    (GO:0046982)
  • Protein homodimerization activity
    (GO:0042803)
  • Regulation of dna-templated transcription
    (GO:0006355)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii-specific dna-binding transcription factor binding
    (GO:0061629)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Transcription regulator complex
    (GO:0005667)
  • Triglyceride homeostasis
    (GO:0070328)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • adipocyte CL0000136
    CSI 26.71
    rCSI 34.3%
    PRS 82.88
  • hepatocyte CL0000182
    CSI 20.72
    rCSI 37.09%
    PRS 89.37
  • centrilobular region hepatocyte CL0019029
    CSI 20.55
    rCSI 53.62%
    PRS 86.85
  • stem cell CL0000034
    CSI 15.47
    rCSI 14.92%
    PRS 86.84
  • epicardial adipocyte CL1000309
    CSI 15.31
    rCSI 49.81%
    PRS 88.1
  • epithelial cell of proximal tubule CL0002306
    CSI 11.49
    rCSI 28.07%
    PRS 84.42
  • cholangiocyte CL1000488
    CSI 9.67
    rCSI 57.95%
    PRS 90.18
  • fallopian tube secretory epithelial cell CL4030006
    CSI 8.22
    rCSI 7.92%
    PRS 89.41
  • choroid plexus epithelial cell CL0000706
    CSI 8.11
    rCSI 13.28%
    PRS 84.05
  • midzonal region hepatocyte CL0019028
    CSI 7.76
    rCSI 18.21%
    PRS 88.49
  • type EC enteroendocrine cell CL0000577
    CSI 6.84
    rCSI 24.28%
    PRS 91.94
  • hepatic stellate cell CL0000632
    CSI 5.98
    rCSI 22.41%
    PRS 86.3
  • enteroendocrine cell of small intestine CL0009006
    CSI 5.62
    rCSI 12.37%
    PRS 93.57
  • innate lymphoid cell CL0001065
    CSI 5.32
    rCSI 10.99%
    PRS 85.23
  • Kupffer cell CL0000091
    CSI 4.75
    rCSI 10.87%
    PRS 91.71
  • periportal region hepatocyte CL0019026
    CSI 4.67
    rCSI 18.17%
    PRS 87.75
  • pancreatic A cell CL0000171
    CSI 4.66
    rCSI 4.88%
    PRS 92.55
  • conventional dendritic cell CL0000990
    CSI 4.11
    rCSI 3.43%
    PRS 85.58
  • type B pancreatic cell CL0000169
    CSI 3.88
    rCSI 8.59%
    PRS 90.8
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.86
    rCSI 6.21%
    PRS 79.12
  • GABAergic neuron CL0000617
    CSI 3.82
    rCSI 12.81%
    PRS 77.78
  • intrahepatic cholangiocyte CL0002538
    CSI 3.61
    rCSI 8.67%
    PRS 90.87
  • pancreatic D cell CL0000173
    CSI 3.42
    rCSI 3.36%
    PRS 92.47
  • enteroendocrine cell CL0000164
    CSI 3.41
    rCSI 4.66%
    PRS 89.33
  • subcutaneous adipocyte CL0002521
    CSI 3.27
    rCSI 16.74%
    PRS 92.55
  • enterocyte CL0000584
    CSI 2.86
    rCSI 4.61%
    PRS 87.86
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.85
    rCSI 3.4%
    PRS 78.22
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.81
    rCSI 3.98%
    PRS 88.72
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.69
    rCSI 4.76%
    PRS 77.62
  • glutamatergic neuron CL0000679
    CSI 2.64
    rCSI 5.43%
    PRS 79.48
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.6
    rCSI 6.21%
    PRS 80.73
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.59
    rCSI 8.09%
    PRS 81.16
  • inhibitory interneuron CL0000498
    CSI 2.5
    rCSI 5.77%
    PRS 81.87
  • intestinal epithelial cell CL0002563
    CSI 2.31
    rCSI 2.42%
    PRS 88.4
  • basal cell of epidermis CL0002187
    CSI 2.25
    rCSI 3.99%
    PRS 62.55
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.22
    rCSI 2.76%
    PRS 76.03
  • colonocyte CL1000347
    CSI 1.86
    rCSI 2.66%
    PRS 89.04
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.84
    rCSI 4.46%
    PRS 76
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.7
    rCSI 6.42%
    PRS 78.35
  • pancreatic PP cell CL0002275
    CSI 1.44
    rCSI 5.71%
    PRS 93.77
  • amacrine cell CL0000561
    CSI 1.43
    rCSI 4.15%
    PRS 82.72
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.39
    rCSI 3.75%
    PRS 92.8
  • type L enteroendocrine cell CL0002279
    CSI 1.32
    rCSI 2.48%
    PRS 92.76
  • enteroendocrine cell of colon CL0009042
    CSI 1.31
    rCSI 6.12%
    PRS 92.88
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.25
    rCSI 1.51%
    PRS 72.13
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.1
    rCSI 3.97%
    PRS 76.17
  • suprabasal keratinocyte CL4033013
    CSI 1.06
    rCSI 1.73%
    PRS 62.37
  • parietal epithelial cell CL1000452
    CSI 0.98
    rCSI 2.63%
    PRS 85.68
  • retinal ganglion cell CL0000740
    CSI 0.98
    rCSI 2.17%
    PRS 80.6
  • kidney connecting tubule epithelial cell CL1000768
    CSI 0.93
    rCSI 2.37%
    PRS 84.81
  • helper T cell CL0000912
    CSI 0.93
    rCSI 1.32%
    PRS 86.86
  • podocyte CL0000653
    CSI 0.91
    rCSI 4.06%
    PRS 91.14
  • paneth cell of epithelium of small intestine CL1000343
    CSI 0.9
    rCSI 2.53%
    PRS 93.64
  • melanocyte of skin CL1000458
    CSI 0.9
    rCSI 1.22%
    PRS 62.28
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.79
    rCSI 4.63%
    PRS 78.6
  • central nervous system neuron CL2000029
    CSI 0.69
    rCSI 5.09%
    PRS 82.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MLXIPL](/details-gene/51085) (MLX Interacting Protein Like) encodes the protein ChREBP (Carbohydrate-responsive element-binding protein), a key transcription factor that orchestrates the cellular response to glucose levels. As a member of the Mlx transcription factor network, it plays a central role in energy homeostasis by regulating the expression of genes involved in glycolysis and lipogenesis [Link](https://doi.org/10.1093/hmg/10.6.617). **Overall**, the expression profile of [MLXIPL](/details-gene/51085) is dominated by metabolically active cells, with the highest significance observed in [adipocyte](/details-cell/CL0000136) (CSI: 26.71) and [hepatocyte](/details-cell/CL0000182) (CSI: 20.72). This expression pattern is highly consistent with its established function as a master regulator of glucose and lipid metabolism. ## Cellular Roles and Expression Landscape The expression landscape of [MLXIPL](/details-gene/51085) underscores its role as a critical sensor and effector of metabolic state, primarily in tissues responsible for nutrient processing and storage. Its profound significance in [adipocyte](/details-cell/CL0000136)s and various [hepatocyte](/details-cell/CL0000182) populations, including [centrilobular region hepatocyte](/details-cell/CL0019029)s, highlights its function in converting excess carbohydrates into fatty acids for storage. Beyond these primary metabolic hubs, [MLXIPL](/details-gene/51085) also shows notable significance in other specialized cell types involved in nutrient handling and secretion. This includes high expression in the [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney, which is responsible for glucose reabsorption, as well as in secretory cells such as [cholangiocyte](/details-cell/CL1000488)s and [fallopian tube secretory epithelial cell](/details-cell/CL4030006)s. Its expression in [enteroendocrine cell of small intestine](/details-cell/CL0009006) suggests a potential role in gut-level nutrient sensing and signaling. The moderate but clear significance in liver-resident immune cells like the [Kupffer cell](/details-cell/CL0000091) and [innate lymphoid cell](/details-cell/CL0001065) may point towards a role in immunometabolism, linking systemic energy status with hepatic immune surveillance. ## Pathways and Molecular Function Functionally, [MLXIPL](/details-gene/51085) operates as a DNA-binding transcription factor with both activator and repressor activities ([GO:0001216](https://www.ebi.ac.uk/QuickGO/term/GO:0001216), [GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227)). Its primary molecular function is to bind carbohydrate response elements ([GO:0035538](https://www.ebi.ac.uk/QuickGO/term/GO:0035538)) in the promoters of target genes, typically as a heterodimer. This activity is central to its role in mediating cellular responses to glucose. The Reactome pathways further illuminate its role as a nexus of metabolic control. [MLXIPL](/details-gene/51085) is a direct effector in the '[Chrebp activates metabolic gene expression](/details-pathway/R-HSA-163765)' pathway, driving processes like fatty acid biosynthesis ([GO:0045723](https://www.ebi.ac.uk/QuickGO/term/GO:0045723)) and glycolysis ([GO:0045821](https://www.ebi.ac.uk/QuickGO/term/GO:0045821)). Its activity is tightly regulated by the energy state of the cell, as shown by its inclusion in pathways like '[Ampk inhibits chrebp transcriptional activation activity](/details-pathway/R-HSA-163680)' and '[Pka-mediated phosphorylation of key metabolic factors](/details-pathway/R-HSA-163358)'. This positions [MLXIPL](/details-gene/51085) as a key component in the broader '[Integration of energy metabolism](/details-pathway/R-HSA-163685)', translating high glucose signals into anabolic programs while being suppressed under conditions of low energy. ## Research Directions The central role of [MLXIPL](/details-gene/51085) in linking carbohydrate metabolism to lipogenesis makes it a critical gene for understanding and potentially treating metabolic disorders. ### Proposed Hypotheses 1. **Role in Hepatic Steatosis:** Given its high expression in [hepatocyte](/details-cell/CL0000182)s and its function in promoting lipid biosynthesis ([GO:0008610](https://www.ebi.ac.uk/QuickGO/term/GO:0008610)), aberrant activation or overexpression of [MLXIPL](/details-gene/51085) in the liver is a likely driver of lipid accumulation and the progression of non-alcoholic fatty liver disease (NAFLD). 2. **Adipocyte Function and Insulin Resistance:** The exceptional significance of [MLXIPL](/details-gene/51085) in [adipocyte](/details-cell/CL0000136)s suggests it is critical for normal adipocyte function. Altered [MLXIPL](/details-gene/51085) activity could impair adipocyte capacity for lipid storage, leading to ectopic lipid deposition in other tissues and contributing to systemic insulin resistance. 3. **Regulation of Immunometabolism:** The expression of [MLXIPL](/details-gene/51085) in [innate lymphoid cell](/details-cell/CL0001065)s and [Kupffer cell](/details-cell/CL0000091)s suggests a hypothesis where it acts as a nutrient sensor that couples metabolic state to immune cell effector function. For example, in a high-glucose environment, [MLXIPL](/details-gene/51085) may promote a pro-inflammatory phenotype in these cells by fueling glycolysis. ### Key Experiment To test the hypothesis that [MLXIPL](/details-gene/51085) is a key driver of NAFLD (Hypothesis 1), a compelling experiment would involve a liver-specific knockout of [MLXIPL](/details-gene/51085) in mice. These knockout mice and wild-type controls would be subjected to a high-fructose, high-fat diet to induce NAFLD. The primary outcomes would be a comparison of liver histology (H&E and Oil Red O staining) to quantify steatosis, measurement of hepatic triglyceride content, and serum levels of liver enzymes (ALT, AST). Furthermore, RNA-sequencing of liver tissue would be performed to confirm the disruption of the lipogenic and glycolytic gene programs normally activated by ChREBP. ### Therapeutic Potential As a transcription factor, [MLXIPL](/details-gene/51085) itself is a challenging direct drug target. However, its central role in metabolic disease makes it an important node for therapeutic intervention. The therapeutic strategy would focus on **inhibition** of its activity or downstream pathways, particularly for conditions like NAFLD, obesity, and hyperlipidemia. This could be achieved by targeting upstream kinases (e.g., AMPK activators) that phosphorylate and inhibit ChREBP activity or by developing small molecules that disrupt its heterodimerization or DNA binding. Such approaches could selectively dampen the lipogenic response to high carbohydrate intake without globally suppressing cellular function, representing a promising avenue for treating metabolic syndrome.

Genular Protein ID: 1323900039

Symbol: MLXPL_HUMAN

Name: Carbohydrate-responsive element-binding protein

UniProtKB Accession Codes:

Q9NP71 C5HU02 C5HU03 C5HU04 Q96E48 Q9BY03 Q9BY04 Q9BY05 Q9BY06 Q9Y2P3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 2 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 15 Ensembl 5 ExpressionAtlas 1 GO 36 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 6 Pumba 1 RNAct 1 Reactome 4 RefSeq 4 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10780788

Title: WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse ortholog.

PubMed ID: 10780788

DOI: 10.1038/sj.ejhg.5200435

PubMed ID: 11230181

Title: WBSCR14, a gene mapping to the Williams-Beuren syndrome deleted region, is a new member of the Mlx transcription factor network.

PubMed ID: 11230181

DOI: 10.1093/hmg/10.6.617

PubMed ID: 9860302

Title: Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes.

PubMed ID: 9860302

DOI: 10.1007/s004390050874

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14759258

Title: An unappreciated role for RNA surveillance.

PubMed ID: 14759258

DOI: 10.1186/gb-2004-5-2-r8

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 852
  • Mass: 93073
  • Checksum: D49E5C3D7C0A72EC
  • Sequence:
    • MAGALAGLAA GLQVPRVAPS PDSDSDTDSE DPSLRRSAGG LLRSQVIHSG HFMVSSPHSD 
SLPRRRDQEG SVGPSDFGPR SIDPTLTRLF ECLSLAYSGK LVSPKWKNFK GLKLLCRDKI 
RLNNAIWRAW YIQYVKRRKS PVCGFVTPLQ GPEADAHRKP EAVVLEGNYW KRRIEVVMRE 
YHKWRIYYKK RLRKPSREDD LLAPKQAEGR WPPPEQWCKQ LFSSVVPVLL GDPEEEPGGR 
QLLDLNCFLS DISDTLFTMT QSGPSPLQLP PEDAYVGNAD MIQPDLTPLQ PSLDDFMDIS 
DFFTNSRLPQ PPMPSNFPEP PSFSPVVDSL FSSGTLGPEV PPASSAMTHL SGHSRLQARN 
SCPGPLDSSA FLSSDFLLPE DPKPRLPPPP VPPPLLHYPP PAKVPGLEPC PPPPFPPMAP 
PTALLQEEPL FSPRFPFPTV PPAPGVSPLP APAAFPPTPQ SVPSPAPTPF PIELLPLGYS 
EPAFGPCFSM PRGKPPAPSP RGQKASPPTL APATASPPTT AGSNNPCLTQ LLTAAKPEQA 
LEPPLVSSTL LRSPGSPQET VPEFPCTFLP PTPAPTPPRP PPGPATLAPS RPLLVPKAER 
LSPPAPSGSE RRLSGDLSSM PGPGTLSVRV SPPQPILSRG RPDSNKTENR RITHISAEQK 
RRFNIKLGFD TLHGLVSTLS AQPSLKVSKA TTLQKTAEYI LMLQQERAGL QEEAQQLRDE 
IEELNAAINL CQQQLPATGV PITHQRFDQM RDMFDDYVRT RTLHNWKFWV FSILIRPLFE 
SFNGMVSTAS VHTLRQTSLA WLDQYCSLPA LRPTVLNSLR QLGTSTSILT DPGRIPEQAT 
RAVTEGTLGK PL