HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MSX1
msh homeobox 1
Chromosome 4 Β· 4p16.2
NCBI Gene: 4487Ensembl: ENSG00000163132.8HGNC: HGNC:7391UniProt: P28360
169PubMed Papers
23Diseases
0Drugs
29Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cell morphogenesisembryonic nail plate morphogenesisprotein localization to nucleusnegative regulation of cell growthorofacial cleft 5Hypodontia - dysplasia of nailstooth agenesis, selective, 1tooth and nail syndrome
✦AI Summary

MSX1 is a transcriptional repressor that functions as a homeobox-containing DNA-binding protein regulating craniofacial and dental development 1. It binds consensus sequences in gene promoters to repress transcription of developmental factors and acts as a stage-specific regulator during odontogenesis, controlling odontoblast differentiation and dental mesenchymal cell proliferation 2. MSX1 phase separation, regulated by PRMT1-catalyzed methylation of its intrinsically disordered region, is essential for embryonic palatal fusion; hypomethylated MSX1 forms abnormal condensates impairing palatal mesenchymal cell proliferation 3. Beyond dentition, MSX1 plays critical roles in heart valve cell differentiation as a key transcription factor mediating endocardial-mesenchymal transition 4, and influences cardiac development through regulation of downstream signaling pathways 5. Clinically, MSX1 mutations cause non-syndromic orofacial clefts, the most common craniofacial birth defect, with specific SNPs showing varying risk associations across populations 67. MSX1 mutations also cause selective tooth agenesis and Witkop syndrome (dental-nail dysplasia), representing major genetic contributions to odontogenic anomalies 28. These findings establish MSX1 as a central developmental regulator with phase separation-dependent mechanisms underlying craniofacial and dental pathologies.

Sources cited
1
MSX1 phase separation regulated by PRMT1 methylation is essential for palatal development; defective phase separation causes cleft palate
PMID: 39843447
2
MSX1 genetic variants influence heart development at embryonic and newborn stages
PMID: 33201861
3
MSX1 is a key transcription factor mediating heart valve cell differentiation and endocardial-mesenchymal transition
PMID: 38357822
4
MSX1 plays crucial roles in epithelial-mesenchymal interactions, cellular proliferation, and differentiation; mutations cause cleft deformities, hypodontia, and Witkop syndrome
PMID: 27259221
5
MSX1 SNPs show significant associations with non-syndromic cleft lip/palate risk, with protective and susceptibility variants identified
PMID: 31132300
6
MSX1 is a major causative gene for tooth agenesis in both syndromic and non-syndromic forms
PMID: 40428404
7
MSX1 gene variant rs3821949 shows increased risk for nonsyndromic cleft lip/palate in Pakistani population
PMID: 37431261
8
MSX1 gene polymorphisms contribute to tooth agenesis risk, though rs12532 shows no significant association
PMID: 40226363
Disease Associationsβ“˜23
orofacial cleft 5Open Targets
0.77Strong
Hypodontia - dysplasia of nailsOpen Targets
0.75Strong
tooth agenesis, selective, 1Open Targets
0.73Strong
tooth and nail syndromeOpen Targets
0.70Strong
cleft lipOpen Targets
0.47Moderate
OligodontiaOpen Targets
0.46Moderate
orofacial cleftOpen Targets
0.44Moderate
genetic disorderOpen Targets
0.41Moderate
cleft palateOpen Targets
0.39Weak
tooth agenesisOpen Targets
0.39Weak
cleft lip/palateOpen Targets
0.39Weak
prostatitisOpen Targets
0.33Weak
allergic rhinitisOpen Targets
0.29Weak
Eczematoid dermatitisOpen Targets
0.28Weak
facial morphologyOpen Targets
0.26Weak
Genu valgumOpen Targets
0.26Weak
Genu varumOpen Targets
0.26Weak
Inguinal herniaOpen Targets
0.24Weak
allergic diseaseOpen Targets
0.23Weak
alcohol drinkingOpen Targets
0.21Weak
Ectodermal dysplasia 3, Witkop typeUniProt
Non-syndromic orofacial cleft 5UniProt
Tooth agenesis, selective, 1UniProt
Pathogenic Variants29
NM_002448.3(MSX1):c.275C>A (p.Ser92Ter)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome|Tooth agenesis, selective, 1
β˜…β˜…β˜†β˜†2025β†’ Residue 92
NM_002448.3(MSX1):c.541_546delinsCTTCA (p.Thr181fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 181
NM_002448.3(MSX1):c.364_365dup (p.Leu123fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 123
NM_002448.3(MSX1):c.250_252delinsC (p.Glu84fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 84
NM_002448.3(MSX1):c.623C>A (p.Ser208Ter)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome|MSX1-related disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 208
NM_002448.3(MSX1):c.691_692del (p.Gln231fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 231
NM_002448.3(MSX1):c.365dup (p.Leu123fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 123
NM_002448.3(MSX1):c.668_669del (p.Arg223fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 223
NM_002448.3(MSX1):c.469+5G>APathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_002448.3(MSX1):c.250G>T (p.Glu84Ter)Likely pathogenic
MSX1-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 84
NM_002448.3(MSX1):c.487dup (p.Ala163fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 163
NM_002448.3(MSX1):c.683dup (p.Arg229fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2021β†’ Residue 229
NM_002448.3(MSX1):c.280C>T (p.Gln94Ter)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 94
NM_002448.3(MSX1):c.655_659del (p.Trp219fs)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2019β†’ Residue 219
NM_002448.3(MSX1):c.661C>T (p.Gln221Ter)Pathogenic
Hypoplastic enamel-onycholysis-hypohidrosis syndrome
β˜…β˜†β˜†β˜†2016β†’ Residue 221
NM_002448.3(MSX1):c.739C>T (p.Pro247Ser)Pathogenic
Tooth agenesis, selective, 1
β˜…β˜†β˜†β˜†β†’ Residue 247
NM_002448.3(MSX1):c.466_469+1delPathogenic
Tooth agenesis, selective, 1
β˜…β˜†β˜†β˜†
NM_002448.3(MSX1):c.547C>T (p.Gln183Ter)Likely pathogenic
MSX1-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 183
NM_002448.3(MSX1):c.519_525dup (p.Arg176Ter)Pathogenic
Orofacial cleft 5
β˜†β˜†β˜†β˜†2021β†’ Residue 176
NM_002448.3(MSX1):c.910_911dup (p.Ter304TyrextTer?)Pathogenic
Tooth agenesis, selective, 1
β˜†β˜†β˜†β˜†2014β†’ Residue 304
View on ClinVar β†—
Related Genes
RUNX2Protein interaction100%IRF6Protein interaction98%BMP4Protein interaction96%SHHProtein interaction92%FGF8Protein interaction91%SATB2Protein interaction88%
Tissue Expression6 tissues
Brain
100%
Ovary
94%
Lung
84%
Heart
56%
Liver
16%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
MSX1RUNX2IRF6BMP4SHHFGF8SATB2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P28360
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.29LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.49–1.29]
RankingsWhere MSX1 stands among ~20K protein-coding genes
  • #2,627of 20,598
    Most Researched169 Β· top quartile
  • #1,839of 5,498
    Most Pathogenic Variants29
  • #13,578of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedMSX1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PRMT1-methylated MSX1 phase separates to control palate development.
PMID: 39843447
Nat Commun Β· 2025
1.00
2
Congenital heart disease risk loci identified by genome-wide association study in European patients.
PMID: 33201861
J Clin Invest Β· 2021
0.90
3
Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.
PMID: 38357822
Circulation Β· 2024
0.80
4
MSX1 gene in the etiology orofacial deformities.
PMID: 27259221
Postepy Hig Med Dosw (Online) Β· 2015
0.70
5
MSX1 gene polymorphisms and non-syndromic cleft lip with or without palate (NSCL/P): A meta-analysis.
PMID: 31132300
Oral Dis Β· 2019
0.60