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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MIXL1
Mix paired-like homeobox
Chromosome 1 · 1q42.12
NCBI Gene: 83881Ensembl: ENSG00000185155.12HGNC: HGNC:13363UniProt: Q9H2W2
14PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingRNA polymerase II-specific DNA-binding transcription factor bindingcis-regulatory region sequence-specific DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificneurodegenerative diseaseacute myeloid leukemianeoplasmbenign prostatic hyperplasia
✦AI Summary

MIXL1 (Mix paired-like homeobox) encodes a paired-type homeobox transcription factor that plays essential roles in early embryonic development and cellular differentiation. During embryogenesis, MIXL1 is transiently expressed in primitive streak-like cells and is required for proper mesendoderm morphogenesis and endoderm formation 12. The gene is transcriptionally regulated by TGF-β signaling through SMAD and FoxH1 binding sites in its promoter, with Nodal identified as a key embryonic regulator 3. MIXL1 expression correlates with enhanced definitive endoderm differentiation efficiency in human induced pluripotent stem cells, and enforced expression can improve endoderm differentiation propensity 4. In hematopoietic development, MIXL1 is expressed in B- and T-cell progenitors and enables isolation of primitive hematopoietic precursors 2. However, MIXL1 also has pathological significance in cancer. High MIXL1 expression is frequently observed in aggressive lymphomas, where it correlates with proliferation index and may contribute to lymphomagenesis 5. In acute myelogenous leukemia, MIXL1 functions as a proto-oncogene by transcriptionally activating c-REL and downstream survival genes BCL2L1 and BCL2A2, and MIXL1-expressing AML cells show sensitivity to BMP receptor inhibitors 6.

Sources cited
1
MIXL1 is transiently co-expressed with Oct4 in differentiating embryonic stem cells, marking mesendodermal precursor stages
PMID: 16433620
2
MIXL1 is expressed in primitive streak-like cells and enables isolation of primitive hematopoietic precursors
PMID: 18032708
3
MIXL1 transcription is regulated by TGF-β signaling through SMAD and FoxH1 binding sites, with Nodal as embryonic regulator
PMID: 15982639
4
MIXL1 activation correlates with enhanced endoderm differentiation efficiency in human iPSCs
PMID: 40280138
5
High MIXL1 expression is frequent in aggressive lymphomas and correlates with proliferation index
PMID: 17303500
6
MIXL1 functions as proto-oncogene in AML by transcriptionally activating c-REL and survival genes
PMID: 25544748
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.42Moderate
acute myeloid leukemiaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
benign prostatic hyperplasiaOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
pulmonary arterial hypertensionOpen Targets
0.02Suggestive
small cell lung carcinomaOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
Hodgkins lymphomaOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
diabetic nephropathyOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
renal fibrosisOpen Targets
0.01Suggestive
B-cell non-Hodgkins lymphomaOpen Targets
0.01Suggestive
hypertrophic cardiomyopathyOpen Targets
0.01Suggestive
idiopathic pulmonary fibrosisOpen Targets
0.01Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.01Suggestive
TremorOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SMAD2Protein interaction86%FOXA2Protein interaction75%TBXTProtein interaction75%EOMESProtein interaction75%FOXH1Protein interaction75%SOX17Protein interaction75%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
72%
Liver
61%
Brain
53%
Heart
39%
Lung
39%
Gene Interaction Network
Click a node to explore
MIXL1SMAD2FOXA2TBXTEOMESFOXH1SOX17
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9H2W2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.92LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.45 [0.84–1.92]
RankingsWhere MIXL1 stands among ~20K protein-coding genes
  • #15,928of 20,598
    Most Researched14
  • #17,436of 17,882
    Most Constrained (LOEUF)1.92
Genes detectedMIXL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Differential expression of the human MIXL1 gene product in non-Hodgkin and Hodgkin lymphomas.
PMID: 17303500
Hum Pathol · 2007
1.00
2
A single-cell and tissue-scale analysis suite resolves Mixl1's role in heart development.
PMID: 40330894
iScience · 2025
0.90
3
A role for BMP-induced homeobox gene MIXL1 in acute myelogenous leukemia and identification of type I BMP receptor as a potential target for therapy.
PMID: 25544748
Oncotarget · 2014
0.80
4
Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors.
PMID: 18032708
Blood · 2008
0.70
5
Mixl1 and oct4 proteins are transiently co-expressed in differentiating mouse and human embryonic stem cells.
PMID: 16433620
Stem Cells Dev · 2005
0.60