SF3B2

Chr 11AD

splicing factor 3b subunit 2

Also known as: CFM, Cus1, HFM, SAP145, SF3B145, SF3b1, SF3b150

NCBI Gene: 10992 ENSG00000087365 UniProt: Q13435 OMIM: 605591

The protein is a component of the U2 snRNP spliceosome complex that removes introns from pre-mRNA and mediates recognition of the intron branch site during RNA splicing. Mutations cause craniofacial microsomia with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that maintaining proper protein levels is critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Craniofacial microsomiaMIM #164210

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Craniofacial microsomia; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 6.00

OE 0.11 (0.06–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.68Z-score

OE missense 0.55 (0.50–0.61)

291 obs / 529.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.06–0.22)

0≤0.351.4

Missense OE?0.55 (0.50–0.61)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 6 / 53.2Missense obs/exp: 291 / 529.5Syn Z: -0.41

Background carrier burden — how many people carry a rare variant somewhere in SF3B2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

815 rare PASS variants

Rare truncating (LoF)

1 in 1,600

54 rare PASS variants

Rare synonymous (reference)

1 in 110

434 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SF3B2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 1,500
South Asian	~43k	1 in 94	1 in 6,000
Remaining (unassigned)	~30k	1 in 110	1 in 2,500
European (Finnish)	~27k	1 in 210	1 in 1,400
Admixed American	~22k	1 in 120	1 in 2,500
African / African American	~21k	1 in 120	1 in 2,200
East Asian	~20k	1 in 110	1 in 2,200
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 22 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 22.? see exons ↓