PUF60: Poly(U) Binding Splicing Factor 60
A key regulator of RNA splicing implicated in developmental disorders and cancer
Gene Information Card
| Symbol | PUF60 |
|---|---|
| Full Name | Poly(U) Binding Splicing Factor 60 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 22827 ncbi.nlm.nih.gov/gene/22827 |
| Ensembl ID | ENSG00000179950 |
| UniProt ID | Q9UHX1 |
| OMIM ID | 604819 |
| HGNC ID | 17042 |
| Aliases | FIR, RoBPI, SIAHBP1, FUSE-binding protein-interacting repressor |
Description
PUF60 encodes a member of the poly(U)-binding splicing factor family. The protein is a component of the spliceosome complex and plays a critical role in pre-mRNA splicing, particularly in the recognition of the 3' splice site. It also functions as a transcriptional repressor by interacting with FUSE-binding protein (FBP) at the far-upstream element (FUSE) of the MYC gene. Alternative splicing results in multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Verheij syndrome | Haploinsufficiency due to heterozygous loss-of-function mutations in PUF60 leads to impaired splicing of multiple target genes, resulting in developmental delay, intellectual disability, and characteristic facial features. | ClinVar, OMIM |
| Colorectal cancer | PUF60 acts as a tumor suppressor; loss of expression or mutation contributes to MYC overexpression and genomic instability. | COSMIC, NCBI |
| Intellectual disability | De novo missense and truncating mutations in PUF60 disrupt RNA splicing, affecting neuronal development. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.4 | Cervical cancer cell line |
| K562 | 18.7 | Leukemia cell line |
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| A549 | 16.9 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.109C>T (p.Arg37*) | Nonsense | Rare | Premature stop, loss of function |
| c.463_464del (p.Leu155fs) | Frameshift | Rare | Frameshift, loss of function |
| c.788G>A (p.Arg263Gln) | Missense | Rare | Likely damaging, affects RNA binding |
Mutation functional classification
Loss of Function (LOF)
Most PUF60 disease-associated mutations are loss-of-function, including nonsense, frameshift, and splice-site variants, leading to haploinsufficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PUF60.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with spliceosome assembly, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • via spliceosome (GO:0000398) |
| • nucleus (GO:0005634) | • spliceosomal complex (GO:0005681) |
| • DNA-templated (GO:0006355) |
Pathways
• mRNA Splicing - Major Pathway (Reactome: R-HSA-72163)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
Protein Summary
PUF60 is a 60 kDa RNA-binding protein that contains three RNA recognition motifs (RRMs) and a U2AF homology motif (UHM). It is a core component of the spliceosome, facilitating 3' splice site recognition. The protein also represses MYC transcription by binding to FBP. Structural studies show that PUF60 interacts with U2AF65 and other splicing factors to modulate exon inclusion.
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