Meis1: A Key Homeobox Transcription Factor in Development and Disease
Comprehensive genomic and functional analysis of Meis1 (Meis Homeobox 1) – a critical regulator of hematopoiesis, neurogenesis, and oncogenesis.
Gene Information Card
| Symbol | Meis1 |
|---|---|
| Full Name | Meis Homeobox 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2p14 |
| NCBI Gene ID | 4211 ncbi.nlm.nih.gov/gene/4211 |
| Ensembl ID | ENSG00000143995 |
| UniProt ID | O00470 |
| OMIM ID | 601739 |
| HGNC ID | 7000 |
| Aliases | MEIS1A, MEIS1B, MGC111080 |
Description
Meis1 (Meis Homeobox 1) encodes a homeobox transcription factor belonging to the TALE (three-amino-acid loop extension) family. It plays essential roles in embryonic development, hematopoiesis, and neurogenesis. Meis1 acts as a cofactor for HOX proteins, regulating target gene expression. Dysregulation of Meis1 is implicated in leukemogenesis, particularly in acute myeloid leukemia (AML) with MLL rearrangements, as well as in neurodevelopmental disorders and vascular malformations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Meis1 overexpression cooperates with HOXA9 or MLL fusions to block differentiation and promote proliferation. | PMID: 15692067; COSMIC; ClinVar |
| Neurodevelopmental disorder with or without brain anomalies | Loss-of-function mutations in Meis1 impair forebrain development, leading to intellectual disability and structural brain defects. | PMID: 31006511; ClinVar |
| Capillary malformation-arteriovenous malformation (CM-AVM) | Heterozygous missense mutations in Meis1 disrupt endothelial cell signaling, causing vascular anomalies. | PMID: 31006511; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Brain (cerebral cortex) | 8.2 | Low |
| Heart | 6.1 | Low |
| Lung | 4.3 | Low |
| Spleen | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.3 | High expression; consistent with role in hematopoiesis |
| HEK293 (embryonic kidney) | 7.1 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 10.4 | High expression; relevant to neurogenesis |
| HepG2 (liver) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1016C>T (p.Pro339Leu) | Missense | <0.1% | Reported in CM-AVM; disrupts DNA-binding affinity |
| c.1243G>A (p.Glu415Lys) | Missense | <0.1% | Associated with neurodevelopmental disorder; reduces transcriptional activity |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Likely loss-of-function; observed in AML |
| c.1420_1421del (p.Leu474fs) | Frameshift | <0.1% | Truncating mutation; loss of homeodomain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations (e.g., p.Leu474fs, p.Met1Val) lead to truncated or absent protein, impairing transcriptional activation and contributing to neurodevelopmental phenotypes.
Gain of Function (GOF)
Overexpression (not point mutations) in AML acts as a gain-of-function by enhancing HOX-mediated leukemogenic transcription.
Dominant Negative (DN)
Missense mutations in the homeodomain (e.g., p.Pro339Leu) may interfere with DNA binding and heterodimerization, exerting dominant-negative effects in vascular development.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0003700) | • Sequence-specific DNA binding (GO:0043565) |
| • Regulation of transcription by RNA polymerase II (GO:0006357) | • Forebrain development (GO:0030900) |
| • Hematopoiesis (GO:0030097) | • Cell differentiation (GO:0030154) |
Pathways
• HOX/MEIS1 signaling in hematopoiesis (Reactome: R-HSA-5619507)
• MLL fusion protein activation of HOXA9/MEIS1 in AML (KEGG: hsa05221)
• TALE homeobox transcription factor network (WikiPathways: WP3661)
Protein Summary
The Meis1 protein (UniProt O00470) is a 390-amino-acid homeobox transcription factor containing a TALE homeodomain and a MEIS domain required for HOX cofactor interaction. It localizes to the nucleus and regulates genes involved in cell proliferation, differentiation, and migration. Post-translational modifications include phosphorylation and sumoylation, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Meis1 Knockout TM4 Cell Line | EDJ-KQ78174 | Mouse | 17268 | Details Get a Quote |
| MEIS1 Knockout HEK293 Cell Line | EDJ-KQ5197 | Human | 4211 | Details Get a Quote |
| MEIS1 Knockout HeLa Cell Line | EDJ-KQ26958 | Human | 4211 | Details Get a Quote |
| MEIS1 Knockout A-549 Cell Line | EDJ-KQ28192 | Human | 4211 | Details Get a Quote |
| MEIS1 Knockout HCT 116 Cell Line | EDJ-KQ70819 | Human | 4211 | Details Get a Quote |
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