Human Gene Module / Chromosome 16 / SF3B3

SF3B3splicing factor 3b subunit 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
25 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
16q22.1
Associated Disorders
-
Relevance to Autism

Musante et al., 2026 collected clinical and molecular information from 24 unrelated individuals with mostly heterozygous missense variants in the SF3B3 gene exhibiting a congruent phenotype including autism spectrum disorder, developmental delay, intellectual disability, language and motor delay, multiple congenital anomalies, and distinctive craniofacial features confirmed by GestaltMatcher analysis; three of the individuals included in this report were ASD probands from the Simons Simplex Collection and the SPARK cohort previously reported in Satterstrom et al., 2020, Zhou et al., 2022, and Trost et al., 2022. Additional functional assessment of fibroblasts from a subset of individuals with SF3B3 missense variants in Musante et al., 2026 identified reduced SF3B3 protein levels, differential gene expression, increased alternative splicing events, and cell-cycle abnormalities compared to controls.

Molecular Function

This gene encodes subunit 3 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. Subunit 3 has also been identified as a component of the STAGA (SPT3-TAF(II)31-GCN5L acetylase) transcription coactivator-HAT (histone acetyltransferase) complex, and the TFTC (TATA-binding-protein-free TAF(II)-containing complex). These complexes may function in chromatin modification, transcription, splicing, and DNA repair.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
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Reports related to SF3B3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Wilfert AB et al. (2021) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Fu JM et al. (2022) Yes -
5 Support - Trost B et al. (2022) Yes -
6 Primary - Luciana Musante et al. () Yes Epilepsy/seizures
Rare Variants   (25)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2669+3_2669+5dup - splice_region_variant De novo - - 35982160 Fu JM et al. (2022)
c.88A>G p.Ile30Val missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2384A>G p.Asn795Ser missense_variant De novo - Simplex 36368308 Trost B et al. (2022)
c.3579C>T p.Val1193= synonymous_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.376A>G p.Lys126Glu missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.452G>A p.Arg151Gln missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.637C>A p.Leu213Ile missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.647G>A p.Gly216Asp missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.656A>C p.His219Pro missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.914C>T p.Thr305Ile missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.1349C>T p.Ser450Phe missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.1480G>A p.Val494Met missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.1574G>A p.Arg525Gln missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.1922G>A p.Cys641Tyr missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.2012A>G p.Asn671Ser missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.2066C>T p.Thr689Ile missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.2183G>C p.Arg728Pro missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.2506G>A p.Ala836Thr missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.3224C>A p.Ala1075Asp missense_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.1205A>C p.Asp402Ala missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1762_1764del p.Val588del inframe_deletion De novo - Simplex 41709284 Luciana Musante et al. ()
c.1390C>T p.Arg464Ter stop_gained Unknown Not maternal Simplex 41709284 Luciana Musante et al. ()
c.2364dupT p.Val789CysfsTer5 frameshift_variant De novo - Simplex 41709284 Luciana Musante et al. ()
c.996_1000del p.Val333ArgfsTer9 frameshift_variant Familial - Simplex 34312540 Wilfert AB et al. (2021)
c.1242_1243insCTGGC p.Asn417TrpfsTer21 frameshift_variant De novo - Simplex 41709284 Luciana Musante et al. ()
Common Variants  

No common variants reported.

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