SF3B2

protein-coding

splicing factor 3b subunit 2, the group of Armadillo like helical domain containing|SF3b complex

Gene summary

This gene encodes subunit 2 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 2 associates with pre-mRNA upstream of the branch site at the anchoring site. Subunit 2 also interacts directly with subunit 4 of the splicing factor 3b complex. Subunit 2 is a highly hydrophilic protein with a proline-rich N-terminus and a glutamate-rich stretch in the C-terminus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006842.3

Inheritance

ClinVar variants

P:10U:121B:14

Top phenotype

Craniofacial microsomia 1

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr11:66,050,729-66,069,308

External References & Databases

Ensembl (ENSG00000087365)

Transcript & Mutation Effects

hg38 • Region Span ~18.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

craniofacial microsomia 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0958175

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Craniofacial microsomia 1AD

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: Individuals have been described with congenital structural cardiovascular anomalies, and surveillance may allow early identification and management

Refs: 34344887

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SF3B2 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 91

not providedTotal: 28

Craniofacial microsomia 1Total: 12

SF3B2-related disorderTotal: 4

not specifiedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006842.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	5 clinvar		8
missense			106 clinvar	9 clinvar		115
nonsense	3 clinvar		1 clinvar			4
start loss	1 clinvar		1 clinvar			2
frameshift	1 clinvar	3 clinvar	2 clinvar			6
splice donor/acceptor (+/-2bp)	2 clinvar		8 clinvar			10
Total	7	3	121	14	0	145

Highest pathogenic variant AF is 0.0000013732001

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006842.3	RefSeq	NP_006833.2	22	MANE Select
ENST00000322535.11	Ensembl	ENSP00000318861.6	22	MANE Select
ENST00000524475.1	Ensembl	ENSP00000435765.1	2	Standard
ENST00000524627.5	Ensembl	ENSP00000435495.1	8	Standard

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

mRNA splicing, via spliceosome
mRNA processing
RNA splicing
viral process

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
spliceosomal complex
U2 snRNP
U12-type spliceosomal complex
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322535
Coding exons: 22
Length: 18580
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.68	291	530	0.550	0.0000309	5831
Missense (PolyPhen)		75	179.34	0.4182		1931
Synonymous	-0.411	203	196	1.04	0.0000107	1760
Loss of Function	6.00	6	53.2	0.113	0.00000305	590

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000068	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00027	0.00025	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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 (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}.;

Recessive Scores

pRec: 0.177

Intolerance Scores

LoFtool: 0.0547
RVIS EVS: -1.09
RVIS percentile EVS: 7.11

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

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