SF3B4

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

Basic information

Region (hg38): 1:149923316-149927803

Links

ENSG00000143368 ∙ NCBI:10262 ∙ OMIM:605593 ∙ HGNC:10771 ∙ Uniprot:Q15427 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acrofacial dysostosis 1, Nager type	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	22541558; 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		2	11	3	17
missense			17	4		21
nonsense	5	1				6
start loss	2					2
frameshift	9	1				10
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	1	2	4
non coding					6	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)
1-149923567-GGGCCTCGAGGGGGAACTGGT-G		Nager syndrome • Malar flattening;Micrognathia;Midface retrusion;Stenosis of the external auditory canal	Pathogenic (Mar 15, 2016)
1-149923582-A-G		Nager syndrome	Uncertain significance (Nov 03, 2022)
1-149923584-TG-T		Nager syndrome	Pathogenic (Sep 07, 2012)
1-149923601-G-A		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
1-149923614-G-C		SF3B4-related disorder	Likely benign (Sep 01, 2021)
1-149923617-AG-A		Nager syndrome	Pathogenic (Sep 07, 2012)
1-149923649-G-A			Likely pathogenic (Jan 06, 2022)
1-149923653-AG-A		Inborn genetic diseases	Pathogenic (Mar 12, 2018)
1-149923657-C-CCAGTGTA			Pathogenic (Aug 17, 2015)
1-149923668-A-AT		Nager syndrome	Pathogenic (Sep 07, 2012)
1-149923669-TG-T		Nager syndrome • Inborn genetic diseases	Pathogenic (Oct 23, 2020)
1-149923669-T-TG		Inborn genetic diseases • not specified • Nager syndrome	Conflicting classifications of pathogenicity (May 04, 2022)
1-149923683-T-A			Likely benign (Sep 30, 2023)
1-149923732-G-C		not specified	Uncertain significance (Jun 29, 2015)
1-149923867-C-CG		Nager syndrome • not specified	Conflicting classifications of pathogenicity (Aug 03, 2023)
1-149923870-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 01, 2023)
1-149923870-G-T		not specified	Conflicting classifications of pathogenicity (Nov 19, 2018)
1-149923874-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 27, 2023)
1-149923888-G-A			Likely benign (Sep 01, 2017)
1-149923922-G-A		Nager syndrome	Pathogenic (Jun 04, 2021)
1-149923922-G-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
1-149923933-T-G		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
1-149923943-A-G		Inborn genetic diseases • SF3B4-related disorder	Benign/Likely benign (Jun 05, 2023)
1-149923950-G-T			Benign (Nov 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SF3B4	protein_coding	protein_coding	ENST00000271628	6	5028

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00824	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.87	70	238	0.294	0.0000126	2708
Missense in Polyphen		2	55.307	0.036161		651
Synonymous	-0.651	97	89.2	1.09	0.00000466	944
Loss of Function	3.51	0	14.4	0.00	9.36e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

• 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

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Sf3b4

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