SMURF1
protein-codingSMAD specific E3 ubiquitin protein ligase 1, the group of HECT domain containing
Gene summary
This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. This protein plays a key roll in the regulation of cell motility, cell signalling, and cell polarity. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SMURF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181349.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | ||||
| missense | 68 | 68 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 72 | 4 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_851994.1 | 18 | MANE Select | |
| Ensembl | ENSP00000355326.2 | 18 | MANE Select | |
| RefSeq | NP_001186776.1 | 18 | Standard | |
| RefSeq | NP_065162.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Endocytosis - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Hedgehog signaling pathway - Homo sapiens (human)
- TGF-Ncore
Biological Process
- protein polyubiquitination
- ubiquitin-dependent protein catabolic process
- protein export from nucleus
- transforming growth factor beta receptor signaling pathway
- ectoderm development
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- phospholipid binding
- activin binding
- ubiquitin protein ligase activity
Cellular Component
- nucleoplasm
- cytoplasm
- mitochondrion
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361125
- Coding exons
- 19
- Length
- 116663
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125747
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.76 | 282 | 446 | 0.632 | 0.0000270 | 4948 |
| Missense (PolyPhen) | 73 | 161.95 | 0.45075 | 1812 | ||
| Synonymous | -0.364 | 201 | 195 | 1.03 | 0.0000136 | 1457 |
| Loss of Function | 4.99 | 10 | 46.9 | 0.213 | 0.00000267 | 491 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23999003}.;
Recessive Scores
- pRec
- 0.169
Intolerance Scores
- LoFtool
- 0.239
- RVIS EVS
- -1.38
- RVIS percentile EVS
- 4.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |