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

ENSG00000108854 ∙ NCBI:64750 ∙ OMIM:605532 ∙ HGNC:16809 ∙ Uniprot:Q9HAU4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMURF2 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	4	9
missense			20	1	2	23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding				1	1	2
Total	0	0	20	7	7

Variants in SMURF2

This is a list of pathogenic ClinVar variants found in the SMURF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-64545855-A-T		not specified	Uncertain significance (Jul 05, 2023)
17-64545925-G-A		not specified	Uncertain significance (Oct 13, 2023)
17-64546296-G-T		not specified	Uncertain significance (Jun 11, 2021)
17-64546301-A-C		not specified	Uncertain significance (May 15, 2023)
17-64547680-T-C		not specified	Uncertain significance (May 11, 2022)
17-64547715-A-G			Benign (Apr 20, 2018)
17-64547747-G-A		not specified	Uncertain significance (May 08, 2023)
17-64551607-T-C		SMURF2-related disorder	Likely benign (Apr 06, 2022)
17-64551654-G-A		not specified	Uncertain significance (Jul 09, 2021)
17-64554961-G-A		not specified	Uncertain significance (Nov 28, 2023)
17-64555928-T-A		not specified	Uncertain significance (May 02, 2024)
17-64557621-G-C		not specified	Uncertain significance (Apr 10, 2023)
17-64557641-T-C		SMURF2-related disorder	Likely benign (Sep 10, 2019)
17-64561554-C-T		not specified	Uncertain significance (Oct 05, 2023)
17-64561602-T-C		not specified	Uncertain significance (Mar 28, 2024)
17-64562840-T-G		not specified	Uncertain significance (Jul 14, 2021)
17-64562965-G-A		not specified	Uncertain significance (Dec 17, 2023)
17-64571788-A-G		SMURF2-related disorder	Likely benign (Dec 06, 2019)
17-64571869-G-A		SMURF2-related disorder	Benign (Apr 20, 2018)
17-64571908-T-C		SMURF2-related disorder	Likely benign (Mar 10, 2023)
17-64571939-T-C		SMURF2-related disorder	Benign (May 16, 2018)
17-64571940-T-C		not specified	Uncertain significance (Aug 16, 2022)
17-64571960-C-A		SMURF2-related disorder	Likely benign (Apr 11, 2019)
17-64580851-C-T		not specified	Uncertain significance (Aug 09, 2021)
17-64580909-C-T		not specified	Uncertain significance (Feb 13, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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