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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SMAD1
SMAD family member 1
Chromosome 4 · 4q31.21
NCBI Gene: 4086Ensembl: ENSG00000170365.11HGNC: HGNC:6767UniProt: Q15797
308PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificDNA-binding transcription activator activity, RNA polymerase II-specificDNA-binding transcription factor activityneurodegenerative diseasedevice complicationhyperaldosteronismovarian dysfunction
✦AI Summary

SMAD1 is a transcriptional modulator that plays crucial roles in bone morphogenetic protein (BMP) signaling pathways and cellular regulation. Upon BMP ligand binding, SMAD1 is phosphorylated by activated BMP type I receptors and associates with SMAD4 to form heteromeric complexes that translocate to the nucleus and function as transcription factors 1. These complexes recognize specific DNA sequences to modulate gene expression in various cellular processes including osteogenesis, vascular remodeling, and myogenic differentiation. SMAD1 promotes osteogenic differentiation, as its downregulation through m6A methylation modifications contributes to postmenopausal osteoporosis 2. In vascular biology, high fluid shear stress suppresses SMAD1 activity through KLF2-BMPER signaling, facilitating arterial outward remodeling 3. SMAD1 also negatively regulates myogenic differentiation of mesoangioblasts, where its inhibition enhances muscle regeneration potential 4. Additionally, SMAD1 exhibits oncogenic properties in glioblastoma by sequestering p300 from p53, reducing p53 acetylation and promoting tumorigenicity and chemoresistance 5. SMAD1 expression is altered in various diseases, being decreased in diabetic nephropathy 6 and pulmonary hypertension associated with congenital heart disease 7, suggesting its potential as a disease biomarker.

Sources cited
1
SMAD1 is part of TGF-beta signaling network involving receptor kinases and nuclear translocation for gene transcription
PMID: 9759503
2
SMAD1 promotes osteogenic differentiation and its downregulation contributes to postmenopausal osteoporosis
PMID: 36319624
3
High fluid shear stress suppresses SMAD1 through KLF2-BMPER signaling to facilitate arterial remodeling
PMID: 39196179
4
SMAD1 negatively regulates myogenic differentiation of mesoangioblasts
PMID: 26450990
5
SMAD1 promotes glioblastoma tumorigenicity by sequestering p300 from p53 and reducing p53 acetylation
PMID: 39629919
6
SMAD1 expression is decreased in diabetic nephropathy patients
PMID: 32184218
7
SMAD1 expression is decreased in children with pulmonary hypertension due to congenital heart disease
PMID: 38410024
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.34Weak
device complicationOpen Targets
0.29Weak
hyperaldosteronismOpen Targets
0.18Weak
ovarian dysfunctionOpen Targets
0.15Weak
pulmonary hypertension, primary, 1Open Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
jaw diseaseOpen Targets
0.09Suggestive
pulmonary arterial hypertensionOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.08Suggestive
strokeOpen Targets
0.07Suggestive
systemic sclerodermaOpen Targets
0.06Suggestive
bladder neck obstructionOpen Targets
0.06Suggestive
glioblastomaOpen Targets
0.06Suggestive
rheumatoid arthritisOpen Targets
0.05Suggestive
posterior cortical atrophyOpen Targets
0.05Suggestive
poisoningOpen Targets
0.05Suggestive
gliomaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SMURF2Protein interaction100%SMURF1Protein interaction100%YAP1Protein interaction100%MAPK3Protein interaction99%LEMD3Protein interaction98%MAPK1Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
82%
Liver
78%
Lung
53%
Ovary
49%
Bone Marrow
38%
Gene Interaction Network
Click a node to explore
SMAD1SMURF2SMURF1YAP1MAPK3LEMD3MAPK1
PROTEIN STRUCTURE
Preparing viewer…
PDB3Q4A · 1.54 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.28Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.13 [0.07–0.28]
RankingsWhere SMAD1 stands among ~20K protein-coding genes
  • #1,120of 20,598
    Most Researched308 · top 10%
  • #993of 17,882
    Most Constrained (LOEUF)0.28 · top 10%
Genes detectedSMAD1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1.
PMID: 36319624
Cell Death Dis · 2022
1.00
2
Glyoxalase System in Breast and Ovarian Cancers: Role of MEK/ERK/SMAD1 Pathway.
PMID: 38785990
Biomolecules · 2024
0.92
3
TGF-beta signal transduction.
PMID: 9759503
Annu Rev Biochem · 1998
0.90
4
PMID: 32184218
J Clin Pathol · 2020
0.80
5
A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling.
PMID: 39196179
Nat Cardiovasc Res · 2024
0.70