U2AF1
protein-codingU2 small nuclear RNA auxiliary factor 1, the group of Spliceosomal A complex|Spliceosomal E complex|RNA binding motif containing
Gene summary
This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising 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 small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
- U2AFBP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to U2AF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006758.3. 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 | 1 | 1 | 2 | |||
| missense | 1 | 9 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 12 | 0 | 1 | 14 |
Highest pathogenic variant AF is 0.000035568904
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006749.1 | 8 | MANE Select | |
| Ensembl | ENSP00000291552.4 | 8 | MANE Select | |
| RefSeq | NP_001020374.1 | 8 | Standard | |
| RefSeq | NP_001020375.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| u2af1 | Danio rerio | Structure: trunk Quality: decreased thickness abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Shigellosis - Homo sapiens (human)
- Spliceosome - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
- spliceosomal assembly
Biological Process
- mRNA splicing, via spliceosome
- mRNA processing
- RNA export from nucleus
- mRNA export from nucleus
- RNA splicing
Molecular Function
- RNA binding
- protein binding
- pre-mRNA 3'-splice site binding
- metal ion binding
Cellular Component
- nucleoplasm
- spliceosomal complex
- Cajal body
- nuclear speck
- catalytic step 2 spliceosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000291552
- Coding exons
- 8
- Length
- 14632
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.85 | 34 | 179 | 0.190 | 0.0000134 | 1563 |
| Missense (PolyPhen) | 5 | 39.552 | 0.12641 | 444 | ||
| Synonymous | 0.713 | 56 | 63.2 | 0.886 | 0.00000445 | 459 |
| Loss of Function | 3.44 | 0 | 13.8 | 0.00 | 6.81e-7 | 172 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a critical role in both constitutive and enhancer- dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. Recruits U2 snRNP to the branch point. Directly mediates interactions between U2AF2 and proteins bound to the enhancers and thus may function as a bridge between U2AF2 and the enhancer complex to recruit it to the adjacent intron. {ECO:0000269|PubMed:22158538, ECO:0000269|PubMed:25311244, ECO:0000269|PubMed:8647433}.;
- Disease
- DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:22158538, ECO:0000269|PubMed:25311244}. Note=The gene represented in this entry may be involved in disease pathogenesis. Mutation altering U2AF1 function in the context of specific RNA sequences can lead to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis. {ECO:0000269|PubMed:25311244}.;
Recessive Scores
- pRec
- 0.170
Intolerance Scores
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |