Human Gene Module / Chromosome 7 / SMURF1

SMURF1SMAD specific E3 ubiquitin protein ligase 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

A de novo splice-site variant in the SMURF1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo missense variant that was predicted to be damaging was identified in this gene in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified SMURF1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SMURF1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Yasser Al-Sarraj et al. (2024) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1888-1G>A - splice_site_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1184C>T p.Pro395Leu missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2170G>A p.Gly724Arg missense_variant De novo - Simplex 38572415 Yasser Al-Sarraj et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo splice-site variant in the SMURF1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo missense variant that was predicted to be damaging was identified in this gene in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified SMURF1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo splice-site variant in the SMURF1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo missense variant that was predicted to be damaging was identified in this gene in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified SMURF1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo splice-site variant in the SMURF1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo missense variant that was predicted to be damaging was identified in this gene in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified SMURF1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

A de novo splice-site variant in the SMURF1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a de novo missense variant that was predicted to be damaging was identified in this gene in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified SMURF1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.49216968161766

Ranking 4696/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99680339121897

Ranking 1386/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Iossifov Probability Score

Score 0.884

Ranking 163/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.21843874582778

Ranking 122/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.19287910722032

Ranking 4376/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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