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GeneBe

SF3B4

splicing factor 3b subunit 4, the group of SF3b complex|RNA binding motif containing

Basic information

Region (hg38): 1:149923316-149927803

Links

ENSG00000143368NCBI:10262OMIM:605593HGNC:10771Uniprot:Q15427AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Nager acrofacial dysostosis (Definitive), mode of inheritance: AD
  • Nager acrofacial dysostosis (Definitive), mode of inheritance: AD
  • Nager acrofacial dysostosis (Strong), mode of inheritance: AD
  • Nager acrofacial dysostosis (Supportive), mode of inheritance: AD
  • acrofacial dysostosis Rodriguez type (Supportive), mode of inheritance: AD
  • SF3B4-related acrofacial dysostosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Acrofacial dysostosis 1, Nager typeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal22541558; 23568615

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SF3B4 gene.

  • not provided (47 variants)
  • Nager syndrome (15 variants)
  • Inborn genetic diseases (14 variants)
  • not specified (9 variants)
  • Hereditary hearing loss and deafness (1 variants)
  • Malar flattening;Micrognathia;Midface retrusion;Stenosis of the external auditory canal (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SF3B4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
2
clinvar
11
clinvar
3
clinvar
17
missense
17
clinvar
4
clinvar
21
nonsense
5
clinvar
1
clinvar
6
start loss
2
clinvar
2
frameshift
9
clinvar
1
clinvar
10
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
splice region
1
1
2
4
non coding
6
clinvar
6
Total 18 3 19 15 9

Variants in SF3B4

This is a list of pathogenic ClinVar variants found in the SF3B4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-149923558-CCTCGAAG-C Nager syndrome Pathogenic (Sep 07, 2012)208827
1-149923567-GGGCCTCGAGGGGGAACTGGT-G Nager syndrome • Malar flattening;Micrognathia;Midface retrusion;Stenosis of the external auditory canal Pathogenic (Mar 15, 2016)212156
1-149923582-A-G Nager syndrome Uncertain significance (Nov 03, 2022)3068612
1-149923584-TG-T Nager syndrome Pathogenic (Sep 07, 2012)208828
1-149923601-G-A Inborn genetic diseases Uncertain significance (Dec 26, 2023)3160834
1-149923614-G-C SF3B4-related condition Likely benign (Sep 01, 2021)3030852
1-149923617-AG-A Nager syndrome Pathogenic (Sep 07, 2012)208829
1-149923649-G-A Likely pathogenic (Jan 06, 2022)1695781
1-149923653-AG-A Inborn genetic diseases Pathogenic (Mar 12, 2018)986287
1-149923657-C-CCAGTGTA Pathogenic (Aug 17, 2015)419756
1-149923668-A-AT Nager syndrome Pathogenic (Sep 07, 2012)208830
1-149923669-TG-T Nager syndrome • Inborn genetic diseases Pathogenic (Oct 23, 2020)31652
1-149923669-T-TG Inborn genetic diseases • not specified • Nager syndrome Conflicting classifications of pathogenicity (May 04, 2022)31651
1-149923683-T-A Likely benign (Sep 30, 2023)2895785
1-149923732-G-C not specified Uncertain significance (Jun 29, 2015)212155
1-149923867-C-CG Nager syndrome • not specified Conflicting classifications of pathogenicity (Aug 03, 2023)208831
1-149923870-G-C Inborn genetic diseases Conflicting classifications of pathogenicity (May 01, 2023)2530379
1-149923870-G-T not specified Conflicting classifications of pathogenicity (Nov 19, 2018)212154
1-149923874-G-A Inborn genetic diseases Conflicting classifications of pathogenicity (Jul 27, 2023)2568526
1-149923888-G-A Likely benign (Sep 01, 2017)708055
1-149923922-G-A Nager syndrome Pathogenic (Jun 04, 2021)65407
1-149923922-G-C Inborn genetic diseases Uncertain significance (Nov 09, 2023)3160833
1-149923933-T-G Inborn genetic diseases Uncertain significance (Jun 11, 2021)2405728
1-149923943-A-G Inborn genetic diseases • SF3B4-related condition Benign/Likely benign (Jun 05, 2023)735055
1-149923950-G-T Benign (Nov 15, 2023)292475

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SF3B4protein_codingprotein_codingENST00000271628 65028
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9920.0082400000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.87702380.2940.00001262708
Missense in Polyphen255.3070.036161651
Synonymous-0.6519789.21.090.00000466944
Loss of Function3.51014.40.009.36e-7161

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). 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. SF3B4 has been found in complex 'B' and 'C' as well (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:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643}.;
Disease
DISEASE: Acrofacial dysostosis 1, Nager type (AFD1) [MIM:154400]: A form of acrofacial dysostosis, a group of disorders which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of AFD1 include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hyoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. {ECO:0000269|PubMed:22541558}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

pRec
0.113

Intolerance Scores

loftool
rvis_EVS
-0.3
rvis_percentile_EVS
32.62

Haploinsufficiency Scores

pHI
0.233
hipred
Y
hipred_score
0.673
ghis
0.532

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.995

Gene Damage Prediction

AllRecessiveDominant
MendelianLowLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerLowLowLow

Mouse Genome Informatics

Gene name
Sf3b4
Phenotype

Zebrafish Information Network

Gene name
sf3b4
Affected structure
trunk
Phenotype tag
abnormal
Phenotype quality
necrotic

Gene ontology

Biological process
RNA splicing, via transesterification reactions;mRNA splicing, via spliceosome;mRNA processing;RNA splicing;positive regulation of mRNA splicing, via spliceosome
Cellular component
nucleus;nucleoplasm;spliceosomal complex;U12-type spliceosomal complex;nucleolus;ribonucleoprotein complex
Molecular function
RNA binding;protein binding