CLP1: Cleavage Factor Polyribonucleotide Kinase Subunit 1
A key RNA processing enzyme involved in tRNA splicing, mRNA 3'-end formation, and neuronal development; mutations cause pontocerebellar hypoplasia type 10 (PCH10).
Gene Information Card
| Symbol | CLP1 |
|---|---|
| Full Name | Cleavage Factor Polyribonucleotide Kinase Subunit 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q12.1 |
| NCBI Gene ID | 10978 ncbi.nlm.nih.gov/gene/10978 |
| Ensembl ID | ENSG00000149311 |
| UniProt ID | Q92989 |
| OMIM ID | 608757 |
| HGNC ID | 2068 |
| Aliases | HEAB, hClp1, Clp1 p47 |
Description
CLP1 encodes a multifunctional RNA processing enzyme with polynucleotide 5'-hydroxyl kinase and 3'-phosphatase activities. It is an essential component of the cleavage and polyadenylation factor (CPF) complex required for mRNA 3'-end formation, and also participates in tRNA splicing by catalyzing the phosphorylation of the 5'-hydroxyl group of the 3' exon. Biallelic loss-of-function mutations in CLP1 cause pontocerebellar hypoplasia type 10 (PCH10), a severe neurodegenerative disorder characterized by microcephaly, motor and intellectual disability, and early-onset epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pontocerebellar hypoplasia type 10 (PCH10) | Biallelic mutations (e.g., p.R140H) impair CLP1 kinase activity, disrupting tRNA splicing and leading to accumulation of unspliced pre-tRNA, neuronal apoptosis, and cerebellar atrophy. | ClinVar, OMIM #615803 |
| Amyotrophic lateral sclerosis (ALS) | Rare heterozygous variants (e.g., p.D205G) have been reported in ALS patients, suggesting a possible contribution to motor neuron vulnerability, though evidence is limited. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.2 | Medium |
| Testis | 8.9 | Medium |
| Heart | 7.1 | Low |
| Liver | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | High expression; commonly used for functional studies |
| HeLa | 11.2 | Medium expression |
| SH-SY5Y | 9.6 | Medium expression; neuronal model |
| K562 | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.419G>A (p.R140H) | Missense | Found in multiple PCH10 families; homozygous | Loss of kinase activity; reduced CLP1 stability; impaired tRNA splicing |
| c.614A>G (p.D205G) | Missense | Rare; reported in ALS | Unknown; possibly partial loss of function |
| c.1A>G (p.M1?) | Start loss | Very rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
p.R140H and p.M1? are loss-of-function; p.R140H reduces kinase activity and protein stability, leading to defective tRNA splicing and neuronal death.
Gain of Function (GOF)
None reported.
Dominant Negative (DN)
Not established; heterozygous carriers of p.R140H are typically unaffected, suggesting recessive inheritance.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • kinase activity (GO:0016301) |
| • polynucleotide 5'-hydroxyl kinase activity (GO:0016779) | • mRNA processing (GO:0006397) |
| • tRNA splicing (GO:0006388) | • nucleus (GO:0005634) |
Pathways
• mRNA 3'-end processing (cleavage and polyadenylation)
• tRNA splicing (via endonuclease complex)
• RNA metabolism
Protein Summary
CLP1 is a 47 kDa nuclear protein that belongs to the Clp1 family. It contains an ATP-binding P-loop motif and exhibits both polynucleotide kinase and 3'-phosphatase activities. As part of the cleavage and polyadenylation factor (CPF), it processes pre-mRNA 3' ends. In tRNA splicing, CLP1 phosphorylates the 5' end of the 3' tRNA exon, enabling ligation. The protein is highly conserved across eukaryotes and is essential for cell viability.
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