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FB2026_01
,
released March 12, 2026
This report describes pontocerebellar hypoplasia, type 10 (PCH10); PCH10 exhibits autosomal recessive inheritance. The human gene implicated in this disease is CLP1, which encodes a multifunctional kinase involved in processing of tRNAs that contain introns. There is a single orthologous gene in Drosophila, cbc, for which multiple genetic reagents have been generated, including classical loss-of-function mutations, RNAi targeting constructs, overexpression constructs, an sgRNA knockout construct, and alleles caused by insertional mutagenesis.
A UAS construct of the human Hsap\CLP1 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Animals homozygous for an amorphic allele of cbc die during the embryonic stage. Animals homozygous for alleles that retain partial function typically die during pupal stages, allowing assessment of larval phenotypes: an overall reduction in brain lobe size and increased cell death is observed in mutant larval brains; larval locomotion is reduced. Tissue-specific effects have been assessed using targeted RNAi: knockdown of cbc in all neurons or motor neurons has a strong effect on pupal and adult viability, as well as larval locomotion; muscle-specific knockdown reduces adult viability.
[updated April 2022 by FlyBase; FBrf0222196]
Multiple subtypes of pontocerebellar hypoplasia have been described. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood. [MedlinePlus, Pontocerebellar hypoplasia; 2022.04.16]
Pontocerebellar hypoplasia (PCH) refers to a group of severe neurodegenerative disorders affecting growth and function of the brainstem and cerebellum, resulting in abnormally small cerebellum and brainstem. [from MIM:607596; 2022.04.16]
[PONTOCEREBELLAR HYPOPLASIA, TYPE 10; PCH10](https://omim.org/entry/615803)
[CLEAVAGE FACTOR POLYNUCLEOTIDE KINASE SUBUNIT 1; CLP1](https://omim.org/entry/608757)
Pontocerebellar hypoplasia type 10 is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy and delayed myelination. Some patients have dysmorphic features and an axonal sensorimotor neuropathy (summary by Karaca et al., 2014, pubmed:24766809; Schaffer et al., 2014, pubmed:24766810). [from MIM:615803; 2022.04.16]
Pontocerebellar hypoplasia type 10 (PCH10) is caused by homozygous mutation in the CLP1 gene. [from MIM:615803; 2022.04.16]
CLP1 encodes a multifunctional kinase which is a component of the tRNA splicing endonuclease complex and a component of the pre-mRNA cleavage complex II. This protein is implicated in tRNA, mRNA, and siRNA maturation. [Gene Cards, CLP1; 2022.04.16]
CLP1 kinase activity serves as a negative regulator of tRNA processing, perturbing exon ligation as well as intron circularization (Hayne et al., 2020; pubmed:32476018).
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human CLP1 (1 Drosophila to 1 human).