MSX1
Chr 4ADmsh homeobox 1
Also known as: ECTD3, HOX7, HYD1, STHAG1
This gene encodes a transcriptional repressor that regulates embryonic development, particularly controlling odontogenesis (tooth development), craniofacial formation including palatal shelf fusion, and nail plate formation. Mutations cause autosomal dominant disorders affecting teeth and orofacial structures, including selective tooth agenesis with or without orofacial clefts, Witkop syndrome (ectodermal dysplasia with nail dysplasia and tooth abnormalities), and isolated orofacial clefts. These conditions typically present at birth or become apparent during early childhood as teeth develop.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
295 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 18 | 4 | 103 | 0 | 125 |
Likely Pathogenic | 5 | 1 | 5 | 0 | 11 |
VUS | 3 | 88 | 8 | 0 | 99 |
Likely Benign | 0 | 11 | 3 | 18 | 32 |
Benign | 0 | 3 | 14 | 2 | 19 |
Conflicting | — | 4 | |||
| Total | 26 | 107 | 133 | 20 | 290 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MSX1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools