SMURF2
SMAD specific E3 ubiquitin protein ligase 2, the group of C2 domain containing|HECT domain containing
Basic information
Region (hg38): 17:64542282-64662307
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (46 variants)
- SMURF2-related_disorder (12 variants)
- not_provided (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMURF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022739.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | |||||
| missense | 45 | 47 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 45 | 8 | 5 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SMURF2 | protein_coding | protein_coding | ENST00000262435 | 19 | 119774 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.872 | 0.128 | 125732 | 0 | 15 | 125747 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.90 | 238 | 402 | 0.593 | 0.0000214 | 4906 |
| Missense in Polyphen | 79 | 171.47 | 0.46071 | 2084 | ||
| Synonymous | 0.914 | 128 | 142 | 0.902 | 0.00000740 | 1381 |
| Loss of Function | 5.30 | 10 | 50.8 | 0.197 | 0.00000314 | 542 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000925 | 0.0000925 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level. {ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440}.;
- Pathway
- TGF-beta signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);WNT-Ncore;TGF-Ncore;TGF-beta Signaling Pathway;Hedgehog Signaling Pathway;Regulation of RUNX3 expression and activity;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Immune System;Adaptive Immune System;Downregulation of SMAD2/3:SMAD4 transcriptional activity;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;TGF-beta super family signaling pathway canonical;Hedgehog ,on, state;Signaling by Hedgehog;Asymmetric localization of PCP proteins;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;PCP/CE pathway;BMP receptor signaling;Beta-catenin independent WNT signaling;BMP Signalling Pathway;Ub-specific processing proteases;Deubiquitination;Signaling by TGF-beta Receptor Complex;ID;Signaling by BMP;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;TCF dependent signaling in response to WNT;TGF-beta receptor signaling;Degradation of AXIN
(Consensus)
Recessive Scores
- pRec
- 0.183
Intolerance Scores
- loftool
- 0.264
- rvis_EVS
- -0.69
- rvis_percentile_EVS
- 15.12
Haploinsufficiency Scores
- pHI
- 0.247
- hipred
- Y
- hipred_score
- 0.819
- ghis
- 0.541
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Smurf2
- Phenotype
- skeleton phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; cellular phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;protein polyubiquitination;ubiquitin-dependent protein catabolic process;protein ubiquitination;protein deubiquitination;regulation of transforming growth factor beta receptor signaling pathway;BMP signaling pathway;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;ubiquitin-dependent SMAD protein catabolic process;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of protein catabolic process;negative regulation of transcription, DNA-templated;Wnt signaling pathway, planar cell polarity pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of trophoblast cell migration
- Cellular component
- ubiquitin ligase complex;nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;nuclear speck;membrane raft
- Molecular function
- ubiquitin-protein transferase activity;transforming growth factor beta receptor binding;protein binding;identical protein binding;SMAD binding;ubiquitin protein ligase activity