Human Gene Module / Chromosome 2 / SF3B1

SF3B1splicing factor 3b subunit 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
35 / 0
Aliases
SF3B1, Hsh155,  MDS,  PRP10,  PRPF10,  SAP155,  SF3b155
Associated Syndromes
-
Chromosome Band
2q33.1
Associated Disorders
-
Relevance to Autism

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018). Uguen et al., 2026 described a cohort of 26 individuals harboring predominantly de novo heterozygous variants in the SF3B1 gene and presenting with a neurodevelopmental disorder characterized by global developmental delay and dysmorphic features, with 9 of these individuals presenting with ASD or autistic features; functional characterization of SF3B1 missense variants identified in this cohort found that they did not cause a loss-of-function effect, although several of these variants did alter splicing.

Molecular Function

This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SF3B1 (7 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 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
4 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity Coe BP , et al. (2018) No -
5 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Recent Recommendation - Kevin Uguen et al. (2026) No ASD, ID, epilepsy/seizures
Rare Variants   (35)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1108C>T p.Pro370Ser missense_variant De novo - - 28135719 et al. (2017)
c.1781G>A p.Arg594Gln missense_variant De novo - - 28135719 et al. (2017)
c.1190G>A p.Arg397His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2585A>T p.Glu862Val missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2759C>G p.Ala920Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.952C>T p.Arg318Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.415+2T>G - splice_site_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.416-1G>T - splice_site_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.456C>A p.Tyr152Ter stop_gained De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.469C>T p.Arg157Ter stop_gained De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.566C>T p.Ala189Val missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.760T>C p.Trp254Arg missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.2938G>T p.Glu980Ter stop_gained De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.890C>A p.Pro297His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1108C>T p.Pro370Ser missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1109C>T p.Pro370Leu missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1606C>A p.Leu536Ile missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1759T>A p.Tyr587Asn missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1837A>G p.Met613Val missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2107A>C p.Thr703Pro missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2164G>A p.Glu722Lys missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2206C>T p.Arg736Cys missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2221A>C p.Lys741Gln missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2339C>T p.Pro780Leu missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2486A>G p.Asn829Ser missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2716G>A p.Glu906Lys missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.2815C>T p.Arg939Cys missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1A>G p.Met1? initiator_codon_variant Unknown Not maternal - 33004838 Wang T et al. (2020)
c.3085G>A p.Glu1029Lys missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.3686C>G p.Ala1229Gly missense_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.496C>T p.Arg166Ter stop_gained Familial Paternal Simplex 41577671 Kevin Uguen et al. (2026)
c.1428_1429insTA p.Lys477Ter frameshift_variant De novo - Simplex 41577671 Kevin Uguen et al. (2026)
c.1190G>A p.Arg397His missense_variant Unknown Not maternal Unknown 41577671 Kevin Uguen et al. (2026)
c.2080del p.Val695TrpfsTer34 frameshift_variant Familial Paternal Simplex 41577671 Kevin Uguen et al. (2026)
c.2427_2428del p.Glu809AspfsTer7 frameshift_variant Familial Maternal Multiplex 41577671 Kevin Uguen et al. (2026)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

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

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

10/1/2020
3
icon
3

Decreased from 3 to 3

Description

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

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

Increased from to 4

Description

De novo missense variants in the SF3B1 gene have been identified in three ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SF3B1 as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Krishnan Probability Score

Score 0.49460202951786

Ranking 3552/25841 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 0.99999997277411

Ranking 160/18225 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 0.905

Ranking 132/239 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 0.51935909594592

Ranking 491/18665 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 0.39816301002998

Ranking 1485/20870 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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