U2AF2
protein-codingU2 small nuclear RNA auxiliary factor 2, the group of RNA binding motif containing|Spliceosomal A complex|Spliceosomal E complex
Gene summary
U2 auxiliary factor (U2AF), comprised of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0957810
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0957810
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0957810
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dental; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to U2AF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007279.3. 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 | 9 | 3 | 15 | ||
| missense | 4 | 9 | 52 | 65 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 4 | 9 | 64 | 9 | 3 | 89 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009210.1 | 12 | MANE Select | |
| Ensembl | ENSP00000307863.3 | 12 | MANE Select | |
| RefSeq | NP_001012496.1 | 12 | Standard | |
| Ensembl | ENSP00000388475.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
- spliceosomal assembly
- RNA Polymerase II Transcription
Biological Process
- mRNA splicing, via spliceosome
- mRNA processing
- RNA export from nucleus
- mRNA export from nucleus
- mRNA 3'-end processing
Molecular Function
- RNA binding
- protein binding
- poly-pyrimidine tract binding
- enzyme binding
- pre-mRNA 3'-splice site binding
Cellular Component
- commitment complex
- Prp19 complex
- nucleus
- nucleoplasm
- spliceosomal complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308924
- Coding exons
- 12
- Length
- 20570
- Individuals with no LoFs
- 124915
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 124947
- p
- 0.000128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.71 | 83 | 320 | 0.259 | 0.0000218 | 3101 |
| Missense (PolyPhen) | 5 | 82.56 | 0.060562 | 831 | ||
| Synonymous | -1.20 | 145 | 128 | 1.13 | 0.00000912 | 931 |
| Loss of Function | 4.39 | 0 | 22.4 | 0.00 | 0.00000109 | 251 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00012 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00025 | 0.00023 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in pre-mRNA splicing and 3'-end processing (PubMed:17024186). By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186). {ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:19470458, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:21536736}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.216
- RVIS EVS
- -0.91
- RVIS percentile EVS
- 9.9
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.962
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |