The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional... See more...

Aliases for MLX Gene

Aliases for MLX Gene

  • MAX Dimerization Protein MLX 2 3 5
  • Class D Basic Helix-Loop-Helix Protein 13 3 4
  • Transcription Factor-Like Protein 4 3 4
  • Max-Like Protein X 3 4
  • BHLHd13 3 4
  • TCFL4 3 4
  • MLX, MAX Dimerization Protein 3
  • Transcription Factor-Like 4 2
  • MAX-Like BHLHZIP Protein 3
  • Max-Like BHLHZip Protein 4
  • MAX-Like Protein X 2
  • BigMax Protein 3
  • Protein BigMax 4
  • BHLHD13 4
  • MAD7 3
  • MXD7 3
  • TF4 3

External Ids for MLX Gene

Previous HGNC Symbols for MLX Gene

  • TCFL4

Previous GeneCards Identifiers for MLX Gene

  • GC17P037973
  • GC17P040719
  • GC17P036483

Summaries for MLX Gene

Entrez Gene Summary for MLX Gene

  • The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional repressors, namely, Mad1 and Mad4. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for MLX Gene

MLX (MAX Dimerization Protein MLX) is a Protein Coding gene. Diseases associated with MLX include Takayasu Arteritis and Pontocerebellar Hypoplasia, Type 12. Among its related pathways are Apoptosis and Autophagy and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is MLXIPL.

UniProtKB/Swiss-Prot Summary for MLX Gene

  • Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation.

Gene Wiki entry for MLX Gene

Additional gene information for MLX Gene

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

Genomics for MLX Gene

GeneHancer (GH) Regulatory Elements for MLX Gene

Promoters and enhancers for MLX Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MLX on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MLX gene promoter:
  • C/EBPalpha
  • Egr-3
  • HNF-4alpha1
  • Pax-2a
  • Pax-6
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for MLX Gene

Genomic Locations for MLX Gene
chr17:42,567,060-42,573,239
(GRCh38/hg38)
Size:
6,180 bases
Orientation:
Plus strand
chr17:40,719,078-40,725,257
(GRCh37/hg19)
Size:
6,180 bases
Orientation:
Plus strand

Genomic View for MLX Gene

Genes around MLX on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MLX Gene

Proteins for MLX Gene

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

    Protein Symbol:
    Q9UH92-MLX_HUMAN
    Recommended name:
    Max-like protein X
    Protein Accession:
    Q9UH92
    Secondary Accessions:
    • A8K2J3
    • B2RAV8
    • B2RD73
    • Q53XM6
    • Q96FL2
    • Q9H2V0
    • Q9H2V1
    • Q9H2V2
    • Q9NXN3

    Protein attributes for MLX Gene

    Size:
    298 amino acids
    Molecular mass:
    33300 Da
    Quaternary structure:
    • Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAD1, MAD4, MNT, WBSCR14 and MLXIP. Can also bind DNA as a homodimer.

    Alternative splice isoforms for MLX Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MLX Gene

Post-translational modifications for MLX Gene

  • Ubiquitination at Lys170 and Lys179
  • Modification sites at PhosphoSitePlus

Other Protein References for MLX Gene

No data available for DME Specific Peptides for MLX Gene

Domains & Families for MLX Gene

Gene Families for MLX Gene

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

Protein Domains for MLX Gene

Suggested Antigen Peptide Sequences for MLX Gene

GenScript: Design optimal peptide antigens:
  • Transcription factor-like protein 4 (MLX_HUMAN)
genes like me logo Genes that share domains with MLX: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for MLX Gene

Function for MLX Gene

Molecular function for MLX Gene

UniProtKB/Swiss-Prot Function:
Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation.

Phenotypes From GWAS Catalog for MLX Gene

Gene Ontology (GO) - Molecular Function for MLX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 10918583
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IMP 10918583
GO:0003677 DNA binding IDA 11230181
GO:0003700 DNA-binding transcription factor activity IBA,NAS 10918583
genes like me logo Genes that share ontologies with MLX: view
genes like me logo Genes that share phenotypes with MLX: view

Human Phenotype Ontology for MLX Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MLX Gene

MGI Knock Outs for MLX:
  • Mlx Mlx<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLX

Clone Products

  • Addgene plasmids for MLX

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for MLX Gene

Localization for MLX Gene

Subcellular locations from UniProtKB/Swiss-Prot for MLX Gene

Isoform Alpha: Cytoplasm. Note=Found predominantly in the cytoplasm (PubMed:10918583). {ECO:0000269 PubMed:10918583}.
Isoform Beta: Cytoplasm. Note=Found predominantly in the cytoplasm (PubMed:10918583). {ECO:0000269 PubMed:10918583}.
Isoform Gamma: Nucleus. Note=Found predominantly in the nucleus (PubMed:10918583). {ECO:0000269 PubMed:10918583}.

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 MLX gene
Compartment Confidence
nucleus 5
cytosol 4
extracellular 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nuclear membrane (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MLX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IBA 10918583
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 10918583
GO:0005829 cytosol IDA --
GO:0031965 nuclear membrane IDA --
genes like me logo Genes that share ontologies with MLX: view

Pathways & Interactions for MLX Gene

genes like me logo Genes that share pathways with MLX: view

Pathways by source for MLX Gene

Gene Ontology (GO) - Biological Process for MLX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 10918583
GO:0006355 regulation of transcription, DNA-templated NAS,IEA 10593926
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0045892 negative regulation of transcription, DNA-templated IDA 11230181
GO:0045944 positive regulation of transcription by RNA polymerase II IDA 11073985
genes like me logo Genes that share ontologies with MLX: view

No data available for SIGNOR curated interactions for MLX Gene

Drugs & Compounds for MLX Gene

(1) Drugs for MLX Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for MLX Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with MLX: view

Transcripts for MLX Gene

mRNA/cDNA for MLX Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MLX

Clone Products

  • Addgene plasmids for MLX

Alternative Splicing Database (ASD) splice patterns (SP) for MLX Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b
SP1: - - - - -
SP2: - - -
SP3: - - -
SP4: - - - - -
SP5: - - -
SP6: - - -
SP7: - - -
SP8: - - - - - - -
SP9: -
SP10: -

Relevant External Links for MLX Gene

GeneLoc Exon Structure for
MLX
ECgene alternative splicing isoforms for
MLX

Expression for MLX Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MLX Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MLX Gene

This gene is overexpressed in Plasma (23.3), Tlymphocyte (16.0), Monocytes (13.4), Neutrophil (6.6), and Brain (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MLX Gene



Protein tissue co-expression partners for MLX Gene

NURSA nuclear receptor signaling pathways regulating expression of MLX Gene:

MLX

SOURCE GeneReport for Unigene cluster for MLX Gene:

Hs.714749

mRNA Expression by UniProt/SwissProt for MLX Gene:

Q9UH92-MLX_HUMAN
Tissue specificity: Expressed in all tissues tested, including spleen, thymus, prostate, ovary, intestine, colon, peripheral blood leukocyte, heart, liver, skeletal muscle and kidney. Lower levels of expression in testis, brain, placenta and lung.

Evidence on tissue expression from TISSUES for MLX Gene

  • Nervous system(4.8)
  • Intestine(4.5)
  • Liver(4.5)
  • Eye(4.2)
  • Heart(3.3)
  • Blood(3.2)
  • Lung(3.2)
  • Muscle(3.1)
  • Kidney(2.5)
  • Skin(2.4)
  • Stomach(2.1)
  • Urine(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MLX Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
Thorax:
  • aorta
  • heart
  • heart valve
  • lung
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • peripheral nervous system
  • red blood cell
  • skin
  • sweat gland
  • white blood cell
genes like me logo Genes that share expression patterns with MLX: view

No data available for mRNA differential expression in normal tissues for MLX Gene

Orthologs for MLX Gene

This gene was present in the common ancestor of animals.

Orthologs for MLX Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MLX 33 32
  • 99.66 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MLX 33
  • 95 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MLX 33
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MLX 33 32
  • 93.97 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MLX 33 32
  • 93.62 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mlx 32
  • 91.05 (n)
mouse
(Mus musculus)
Mammalia Mlx 17 33 32
  • 90.49 (n)
chicken
(Gallus gallus)
Aves MLX 33 32
  • 79.69 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MLX 33
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mlx 32
  • 74.75 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.15007 32
zebrafish
(Danio rerio)
Actinopterygii mlx 33 32
  • 75.46 (n)
OneToOne
-- 32
fruit fly
(Drosophila melanogaster)
Insecta bigmax 33 32
  • 60.41 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000682 32
  • 57.82 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 41 (a)
OneToOne
Species where no ortholog for MLX was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • 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 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)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MLX Gene

ENSEMBL:
Gene Tree for MLX (if available)
TreeFam:
Gene Tree for MLX (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MLX: view image

Paralogs for MLX Gene

Paralogs for MLX Gene

(2) SIMAP similar genes for MLX Gene using alignment to 2 proteins:

  • MLX_HUMAN
  • K7EID0_HUMAN

Pseudogenes.org Pseudogenes for MLX Gene

genes like me logo Genes that share paralogs with MLX: view

Variants for MLX Gene

Sequence variations from dbSNP and Humsavar for MLX Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs140709867 pathogenic, Neurodegeneration with brain iron accumulation 6 42,565,668(+) C/A/T upstream_transcript_variant
rs146857074 uncertain-significance, Neurodegeneration with brain iron accumulation 6 42,565,476(+) C/A/T upstream_transcript_variant
rs1555625395 uncertain-significance, Neurodegeneration with brain iron accumulation 6 42,565,968(+) AAAA/AA upstream_transcript_variant
rs577714887 pathogenic, PONTOCEREBELLAR HYPOPLASIA, TYPE 12 42,565,656(+) C/G upstream_transcript_variant
rs74886553 benign, not specified, Neurodegeneration with brain iron accumulation 6 42,565,654(+) C/G/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for MLX Gene

Variant ID Type Subtype PubMed ID
esv33998 OTHER inversion 15654335
nsv1064012 CNV gain 25217958
nsv1146669 OTHER inversion 26484159

Variation tolerance for MLX Gene

Residual Variation Intolerance Score: 21.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.65; 91.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MLX Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MLX

SNP Genotyping and Copy Number Assay Products

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

Disorders for MLX Gene

MalaCards: The human disease database

(3) MalaCards diseases for MLX Gene - From: Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MLX in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MLX

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MLX: view

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

Publications for MLX Gene

  1. Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway? (PMID: 10918583) Meroni G … Reymond A (Oncogene 2000) 3 4 23 56
  2. Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors. (PMID: 10593926) Billin AN … Ayer DE (The Journal of biological chemistry 1999) 3 4 23 56
  3. TCFL4: a gene at 17q21.1 encoding a putative basic helix-loop-helix leucine-zipper transcription factor. (PMID: 8973301) Bjerknes M … Cheng H (Gene 1996) 2 3 23 56
  4. Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. (PMID: 18458340) Stoltzman CA … Ayer DE (Proceedings of the National Academy of Sciences of the United States of America 2008) 3 23 56
  5. MondoA-Mlx heterodimers are candidate sensors of cellular energy status: mitochondrial localization and direct regulation of glycolysis. (PMID: 16782875) Sans CL … Ayer DE (Molecular and cellular biology 2006) 3 4 56

Products for MLX Gene

Sources for MLX Gene