SMURF1

SMAD specific E3 ubiquitin protein ligase 1, the group of HECT domain containing

Basic information

Region (hg38): 7:99027439-99144108

Links

ENSG00000198742 ∙ NCBI:57154 ∙ OMIM:605568 ∙ HGNC:16807 ∙ Uniprot:Q9HCE7 ∙ 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 SMURF1 gene.

• Inborn genetic diseases (17 variants)
• not provided (4 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMURF1 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				2	1	3
missense			18			18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	18	2	2

Variants in SMURF1

This is a list of pathogenic ClinVar variants found in the SMURF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-99030655-C-T		not specified	Uncertain significance (Feb 02, 2024)
7-99030675-C-T		not specified	Uncertain significance (Jun 06, 2022)
7-99033104-C-T		not specified	Uncertain significance (Oct 12, 2022)
7-99033116-T-C		not specified	Uncertain significance (May 27, 2022)
7-99035506-G-A			Benign (Feb 20, 2018)
7-99035601-G-A		not specified	Uncertain significance (Jun 16, 2023)
7-99037119-T-C		not specified	Uncertain significance (Aug 01, 2023)
7-99038389-G-A		not specified	Uncertain significance (May 27, 2022)
7-99038400-T-G		not specified	Uncertain significance (May 01, 2022)
7-99038452-G-A		not specified	Uncertain significance (Dec 21, 2023)
7-99040487-T-A		not specified	Uncertain significance (Nov 10, 2022)
7-99042136-C-T			Likely benign (Oct 01, 2023)
7-99042164-T-G		not specified	Uncertain significance (Aug 21, 2023)
7-99047708-T-C			Likely benign (Jul 01, 2022)
7-99047734-G-A		not specified	Uncertain significance (Jan 23, 2024)
7-99047752-C-T		not specified	Uncertain significance (Sep 14, 2022)
7-99047860-G-A		not specified	Uncertain significance (Oct 24, 2023)
7-99049628-T-C		not specified	Uncertain significance (Aug 17, 2021)
7-99049631-C-A		not specified	Uncertain significance (Oct 03, 2022)
7-99050949-C-T		not specified	Uncertain significance (Jul 25, 2023)
7-99052205-C-T		not specified	Uncertain significance (Mar 25, 2021)
7-99052235-G-A		not specified	Uncertain significance (Dec 17, 2023)
7-99052279-T-A		not specified	Uncertain significance (Dec 28, 2022)
7-99052321-C-T		not specified	Uncertain significance (Dec 06, 2021)
7-99052427-C-T		not specified	Uncertain significance (Feb 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMURF1	protein_coding	protein_coding	ENST00000361125	19	116663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.612	0.388	125739	0	8	125747	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.76	282	446	0.632	0.0000270	4948
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Bone Morphogenic Protein (BMP) Signalling and Regulation;Ectoderm Differentiation;TGF-beta Signaling Pathway;Hedgehog Signaling Pathway;Transcriptional regulation by RUNX2;Regulation of RUNX3 expression and activity;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;estrogen responsive protein efp controls cell cycle and breast tumors growth;Generic Transcription Pathway;RNA Polymerase II Transcription;Immune System;Adaptive Immune System;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;PCP/CE pathway;BMP receptor signaling;Beta-catenin independent WNT signaling;Signaling by TGF-beta Receptor Complex;Signaling by BMP;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs;Signaling events mediated by HDAC Class I;TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition);TGF-beta receptor signaling;Regulation of RUNX2 expression and activity (Consensus)

Recessive Scores

• pRec: 0.169

Intolerance Scores

• loftool: 0.239
• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.39

Haploinsufficiency Scores

• pHI: 0.345
• hipred: Y
• hipred_score: 0.792
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smurf1
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; 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; 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; skeleton phenotype

Gene ontology

• Biological process: protein polyubiquitination;ubiquitin-dependent protein catabolic process;protein export from nucleus;transforming growth factor beta receptor signaling pathway;ectoderm development;protein ubiquitination;cell differentiation;negative regulation of ossification;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;receptor catabolic process;protein localization to cell surface;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of protein catabolic process;Wnt signaling pathway, planar cell polarity pathway;parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization;engulfment of target by autophagosome;substrate localization to autophagosome;protein targeting to vacuole involved in autophagy;protein localization to plasma membrane;positive regulation of dendrite extension;positive regulation of ubiquitin-dependent protein catabolic process
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;cytosol;plasma membrane;axon;neuronal cell body;extracellular exosome
• Molecular function: ubiquitin-protein transferase activity;protein binding;phospholipid binding;activin binding;ubiquitin protein ligase activity;I-SMAD binding;R-SMAD binding