SMAD1

Chr 4

SMAD family member 1

Also known as: BSP-1, BSP1, JV4-1, JV41, MADH1, MADR1

The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
congenital heart disease · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
1
Active trials
245
Pubs (1 yr)
P/LP submissions
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· predicted
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GeneReview available — SMAD1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.27LOEUF
pLI 0.988
Z-score 3.69
OE 0.06 (0.020.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.28Z-score
OE missense 0.60 (0.530.69)
159 obs / 263.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.020.27)
00.351.4
Missense OE?0.60 (0.530.69)
00.61.4
Synonymous OE?1.09
01.21.6
LoF obs/exp: 1 / 17.8Missense obs/exp: 159 / 263.1Syn Z: -0.68

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SMAD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.