MLXIPL MLX interacting protein like [Homo sapiens (human)] - Gene

Summary

Official Symbol: MLXIPLprovided by HGNC
Official Full Name: MLX interacting protein likeprovided by HGNC
Primary source: HGNC:HGNC:12744
See related: Ensembl:ENSG00000009950 MIM:605678; AllianceGenome:HGNC:12744
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: MIO; MLX; CHREBP; MONDOB; WBSCR14; WS-bHLH; bHLHd14
Summary: This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Expression: Biased expression in fat (RPKM 35.0), liver (RPKM 27.7) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q11.23

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (73593202..73647907, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (74794073..74848925, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (73007532..73038852, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.
Title: A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.
Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity.
Title: Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity.
Knockdown of ChREBP ameliorates retinal microvascular endothelial cell injury and angiogenic responses in diabetic retinopathy.
Title: Knockdown of ChREBP ameliorates retinal microvascular endothelial cell injury and angiogenic responses in diabetic retinopathy.
ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits.
Title: ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits.
The role of ChREBP in carbohydrate sensing and NAFLD development.
Title: The role of ChREBP in carbohydrate sensing and NAFLD development.
New insights into the inter-organ crosstalk mediated by ChREBP.
Title: New insights into the inter-organ crosstalk mediated by ChREBP.
MLXIPL promotes the migration, invasion, and glycolysis of hepatocellular carcinoma cells by phosphorylation of mTOR.
Title: MLXIPL promotes the migration, invasion, and glycolysis of hepatocellular carcinoma cells by phosphorylation of mTOR.
HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis.
Title: HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis.
Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.
Title: Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.
Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP.
Title: Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP.

Submit: New GeneRIF Correction See all GeneRIFs (87)

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
Williams syndrome MedGen: C0175702 OMIM: 194050 GeneReviews: Williams Syndrome	Compare labs

EBI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 30 loci contribute to polygenic dyslipidemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants influencing circulating lipid levels and risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. EBI GWAS Catalog EBI GWAS CatalogPubMed
Newly identified loci that influence lipid concentrations and risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D7S2476 (e-PCR), detects polymorphism
- UniSTS:54018

D7S2476 (e-PCR), detects polymorphism
- UniSTS:60951

PMC156606P4 (e-PCR)
- UniSTS:271411

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-107367 (e-PCR)
- UniSTS:170333

D10S16 (e-PCR)
- UniSTS:155756

Wbscr14 (e-PCR), detects polymorphism
- UniSTS:230801

Wbscr14 (e-PCR), detects polymorphism
- UniSTS:230802

D7S809 (e-PCR)
- UniSTS:148631

RH64919 (e-PCR)
- UniSTS:73928

G60573 (e-PCR)
- UniSTS:137679

D7S1624 (e-PCR)
- UniSTS:19709

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to DNA binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables DNA binding	NAS Non-traceable Author Statement more info	PubMed
enables DNA-binding transcription activator activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity	NAS Non-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 DNA-binding transcription factor binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation 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-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables carbohydrate response element binding	TAS Traceable Author Statement more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
NOT enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in fatty acid homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in glucose mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of oxidative phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fatty acid biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lipid biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of transcription from RNA polymerase II promoter by glucose	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in triglyceride homeostasis	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of transcription regulator complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: carbohydrate-responsive element-binding protein

Names: Mlx interactor; WS basic-helix-loop-helix leucine zipper protein; Williams Beuren syndrome chromosome region 14; Williams-Beuren syndrome chromosome region 14 protein 1; Williams-Beuren syndrome chromosome region 14 protein 2; Williams-Beuren syndrome chromosome region 14 protein 3; carbohydrate response element binding protein; class D basic helix-loop-helix protein 14; williams-Beuren syndrome chromosomal region 14 protein

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

NG_009307.2 RefSeqGene

Range

28385..59705

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_032951.3 → NP_116569.1 carbohydrate-responsive element-binding protein isoform alpha

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (alpha).

Source sequence(s)

AF156603, AF245470, BC012925

Consensus CDS

CCDS5553.1

UniProtKB/Swiss-Prot

C5HU02, C5HU03, C5HU04, Q96E48, Q9BY03, Q9BY04, Q9BY05, Q9BY06, Q9NP71, Q9Y2P3

UniProtKB/TrEMBL

C5HU01

Related

ENSP00000320886.3, ENST00000313375.8

Conserved Domains (2) summary

cd00083
Location:648 → 708

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, ...

cl21462
Location:694 → 735

bZIP; Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain
NM_032952.3 → NP_116570.1 carbohydrate-responsive element-binding protein isoform beta

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform beta).

Source sequence(s)

AF156603, AF245471, BC012925

Consensus CDS

CCDS47605.1

UniProtKB/TrEMBL

C5HU01

Related

ENSP00000406296.2, ENST00000429400.6

Conserved Domains (1) summary

cd00083
Location:648 → 680

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, ...
NM_032953.3 → NP_116571.1 carbohydrate-responsive element-binding protein isoform gamma

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform gamma).

Source sequence(s)

AF156603, AF245472, BC012925

Consensus CDS

CCDS47606.1

UniProtKB/TrEMBL

C5HU01

Related

ENSP00000412330.2, ENST00000414749.6

Conserved Domains (2) summary

cd00083
Location:645 → 706

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, ...

cl21462
Location:692 → 733

bZIP; Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain
NM_032954.3 → NP_116572.1 carbohydrate-responsive element-binding protein isoform delta

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform delta).

Source sequence(s)

AF156603, AF245473, BC012925

Consensus CDS

CCDS5554.1

UniProtKB/TrEMBL

C5HU01

Related

ENSP00000346629.1, ENST00000354613.5

Conserved Domains (1) summary

cd00083
Location:645 → 678

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, ...

RNA

NR_134541.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF245474, BC012925, BG772360

Related

ENST00000345114.9

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

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

73593202..73647907 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047420437.1 → XP_047276393.1 carbohydrate-responsive element-binding protein isoform X9
XM_047420435.1 → XP_047276391.1 carbohydrate-responsive element-binding protein isoform X7
XM_047420433.1 → XP_047276389.1 carbohydrate-responsive element-binding protein isoform X5

Related

ENSP00000392636.1, ENST00000434326.5
XM_047420434.1 → XP_047276390.1 carbohydrate-responsive element-binding protein isoform X6
XM_047420432.1 → XP_047276388.1 carbohydrate-responsive element-binding protein isoform X4
XM_011516278.2 → XP_011514580.1 carbohydrate-responsive element-binding protein isoform X2

UniProtKB/TrEMBL

C5HU01

Conserved Domains (2) summary

cd00083
Location:712 → 772

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, ...

pfam08614
Location:651 → 792

ATG16; Autophagy protein 16 (ATG16)
XM_011516279.2 → XP_011514581.1 carbohydrate-responsive element-binding protein isoform X3

UniProtKB/TrEMBL

C5HU01

Conserved Domains (1) summary

cd00083
Location:713 → 769

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, ...
XM_011516277.2 → XP_011514579.1 carbohydrate-responsive element-binding protein isoform X1

UniProtKB/TrEMBL

C5HU01

Conserved Domains (2) summary

cd00083
Location:713 → 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, ...

pfam08614
Location:652 → 793

ATG16; Autophagy protein 16 (ATG16)
XM_047420436.1 → XP_047276392.1 carbohydrate-responsive element-binding protein isoform X8
XM_017012263.2 → XP_016867752.1 carbohydrate-responsive element-binding protein isoform X10

RNA

XR_007060040.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

74794073..74848925 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054358326.1 → XP_054214301.1 carbohydrate-responsive element-binding protein isoform X9
XM_054358324.1 → XP_054214299.1 carbohydrate-responsive element-binding protein isoform X7
XM_054358322.1 → XP_054214297.1 carbohydrate-responsive element-binding protein isoform X5
XM_054358323.1 → XP_054214298.1 carbohydrate-responsive element-binding protein isoform X6
XM_054358321.1 → XP_054214296.1 carbohydrate-responsive element-binding protein isoform X4
XM_054358319.1 → XP_054214294.1 carbohydrate-responsive element-binding protein isoform X2
XM_054358320.1 → XP_054214295.1 carbohydrate-responsive element-binding protein isoform X3
XM_054358318.1 → XP_054214293.1 carbohydrate-responsive element-binding protein isoform X1
XM_054358325.1 → XP_054214300.1 carbohydrate-responsive element-binding protein isoform X8
XM_054358327.1 → XP_054214302.1 carbohydrate-responsive element-binding protein isoform X10

RNA

XR_008487623.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_032994.2: Suppressed sequence

Description

NM_032994.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.