SF3B4

Chr 1AD

splicing factor 3b subunit 4

Also known as: AFD1, Hsh49, SAP49, SF3b49

NCBI Gene: 10262 ENSG00000143368 UniProt: Q15427 OMIM: 605593

The protein is a component of the SF3B subcomplex within the U2 snRNP spliceosome that recognizes branch sites and promotes pre-mRNA splicing. Mutations cause acrofacial dysostosis 1 (Nager type), which primarily affects craniofacial and limb development, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that heterozygous mutations are likely sufficient to cause disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Acrofacial dysostosis 1, Nager typeMIM #154400

Clinical highlights

Gene-disease validity (ClinGen)

SF3B4-related acrofacial dysostosis · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· G2P