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MSX1

Chr 4p16.2

msh homeobox 1

Aliases:
HYD1, OFC5
MANE:
ENST00000382723.5

Annotations refreshed 10 hours ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Clefting

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Ectodermal dysplasia

    BOTH monoallelic and biallelic, autosomal or pseudoautosomal
  • Ectodermal dysplasia without a known gene mutation

    BOTH monoallelic and biallelic, autosomal or pseudoautosomal
  • Fetal anomalies

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Intellectual disability

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

  • orofacial cleft 5

    0.76
  • Hypodontia - dysplasia of nails

    0.74
  • tooth agenesis, selective, 1

    0.73
  • tooth and nail syndrome

    0.70
  • tooth agenesis

    0.48
  • cleft lip

    0.47
  • Oligodontia

    0.46
  • hereditary disease

    0.41
  • cleft palate

    0.40
  • cleft lip/palate

    0.39

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Homeobox protein MSX-1

Acts as a transcriptional repressor (By similarity). Capable of transcription autoinactivation (By similarity). Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR (By similarity). Represses transcription of myoblast differentiation factors (By similarity). Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1 (By similarity). Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells (By similarity). At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells (By similarity). May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme (By similarity). Required for BMP4 expression in dental mesenchyme cells (By similarity). Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells (By similarity). Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells (By similarity). Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells (By similarity). At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle (By similarity). Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN (By similarity). Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation (By similarity). Plays a role in embryonic bone formation of the middle ear, skull and nasal bones (By similarity). Required for correct formation and thickness of the nail plate (By similarity). May play a role in limb-pattern formation (By similarity)

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.