U2AF1

U2 small nuclear RNA auxiliary factor 1, the group of Spliceosomal A complex|Spliceosomal E complex|RNA binding motif containing

Basic information

Region (hg38): 21:43092955-43107570

Previous symbols: [ "U2AFBP" ]

Links

ENSG00000160201 ∙ NCBI:7307 ∙ OMIM:191317 ∙ HGNC:12453 ∙ Uniprot:Q01081 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the U2AF1 gene.

• Inborn genetic diseases (2 variants)
• not provided (1 variants)
• Acute myeloid leukemia (1 variants)
• Myelodysplastic syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the U2AF1 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						0
missense		1	2			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	2	0	0

Highest pathogenic variant AF is 0.0000731

Variants in U2AF1

This is a list of pathogenic ClinVar variants found in the U2AF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-43093182-C-T		not specified	Uncertain significance (Nov 17, 2022)
21-43093188-C-T		not specified	Uncertain significance (Aug 21, 2023)
21-43094667-T-C		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
21-43094667-T-G		Acute myeloid leukemia • Myelodysplastic syndrome	Likely pathogenic (Mar 15, 2022)
21-43104346-G-A		Transitional cell carcinoma of the bladder • Squamous cell carcinoma of the head and neck • Pancreatic adenocarcinoma • Acute myeloid leukemia • Lung adenocarcinoma • Neoplasm of uterine cervix • Myelodysplastic syndrome • Uterine carcinosarcoma • Malignant neoplasm of body of uterus	Likely pathogenic (May 31, 2016)
21-43104346-G-T		Acute myeloid leukemia • Transitional cell carcinoma of the bladder • Myelodysplastic syndrome • Squamous cell carcinoma of the head and neck • Uterine carcinosarcoma • Malignant neoplasm of body of uterus • Pancreatic adenocarcinoma • Lung adenocarcinoma • Neoplasm of uterine cervix	Likely pathogenic (May 31, 2016)
21-43104348-G-A		U2AF1-related disorder	Benign (Sep 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
U2AF1	protein_coding	protein_coding	ENST00000291552	8	14632

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0101	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.85	34	179	0.190	0.0000134	1563
Missense in 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

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: 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}.
• Pathway: Shigellosis - Homo sapiens (human);Spliceosome - Homo sapiens (human);mRNA Processing;Gene expression (Transcription);spliceosomal assembly;RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.170

Intolerance Scores

• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.302
• hipred: Y
• hipred_score: 0.748
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.979

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: U2af1

Zebrafish Information Network

• Gene name: u2af1
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: decreased thickness

Gene ontology

• Biological process: mRNA splicing, via spliceosome;mRNA processing;RNA export from nucleus;mRNA export from nucleus;RNA splicing;mRNA 3'-end processing
• Cellular component: nucleoplasm;spliceosomal complex;Cajal body;nuclear speck;catalytic step 2 spliceosome;U2AF
• Molecular function: RNA binding;protein binding;pre-mRNA 3'-splice site binding;metal ion binding