GeneBe

SF3B3

protein-coding

splicing factor 3b subunit 3, the group of SF3b complex|Small nucleolar RNA protein coding host genes

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012426.5

Inheritance

—

ClinVar variants

U:81

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr16:70,523,791-70,577,670

External References & Databases

Ensembl (ENSG00000189091)NCBI Gene (23450)OMIM (605592)HGNC:10770GenCCUniProt (Q15393)AlphaFoldClinVar (SF3B3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~53.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SF3B3 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 62
not providedTotal: 4
Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012426.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
72
clinvar
 72
nonsense
2
clinvar
 2
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total00810081
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012426.5RefSeqNP_036558.325MANE Select
ENST00000302516.10EnsemblENSP00000305790.525MANE Select
ENST00000564899.1EnsemblENSP00000461342.11Standard
ENST00000566095.6EnsemblENSP00000454308.22Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Spliceosome - Homo sapiens (human)
  • mRNA Processing
  • Metabolism of RNA
  • mRNA Splicing - Major Pathway
  • mRNA Splicing - Minor Pathway

Biological Process

  • RNA splicing, via transesterification reactions
  • mRNA splicing, via spliceosome
  • negative regulation of protein catabolic process

Molecular Function

  • nucleic acid binding
  • protein binding
  • protein-containing complex binding

Cellular Component

  • nucleus
  • nucleoplasm
  • spliceosomal complex
  • U12-type spliceosomal complex
  • nucleolus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000302516
Coding exons
25
Length
51130
Individuals with no LoFs
125735
Homozygous LoFs
0
Heterozygous LoFs
10
Defined
125745
p
0.0000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense5.183086920.4450.00003827934
Missense (PolyPhen)62264.090.234772991
Synonymous-0.9262802611.070.00001372467
Loss of Function6.87666.40.09040.00000410710

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000620.000062rare
South Asian00.0absent
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome (PubMed:10490618, PubMed:10882114, PubMed:27720643, PubMed:28781166). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077). {ECO:0000269|PubMed:10490618, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:28781166}.;

Recessive Scores

pRec
0.203

Intolerance Scores

LoFtool
0.274
RVIS EVS
-1.02
RVIS percentile EVS
8.04

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.866

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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