CLP1

cleavage factor polyribonucleotide kinase subunit 1

Basic information

Region (hg38): 11:57648188-57661865

Links

ENSG00000172409 ∙ NCBI:10978 ∙ OMIM:608757 ∙ HGNC:16999 ∙ Uniprot:Q92989 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 10 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 10 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 10 (Limited), mode of inheritance: AR
• pontocerebellar hypoplasia type 10 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 10 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	24766809; 24766810; 29307788

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLP1 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			1	28	5	34
missense		1	45	2		48
nonsense		1	1			2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				4	2	6
Total	0	2	48	34	7

Variants in CLP1

This is a list of pathogenic ClinVar variants found in the CLP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-57657849-C-T		not specified	Likely benign (Oct 17, 2017)
11-57657867-T-TA		not specified	Likely benign (Jan 18, 2018)
11-57659239-A-G			Benign (Jun 30, 2018)
11-57659488-G-A			Likely benign (Aug 29, 2022)
11-57659524-A-C		Inborn genetic diseases	Uncertain significance (Jan 28, 2022)
11-57659525-C-A			Uncertain significance (Apr 03, 2023)
11-57659531-C-T		Pontoneocerebellar hypoplasia	Likely pathogenic (Nov 16, 2022)
11-57659566-T-A			Likely benign (Dec 18, 2023)
11-57659579-T-C			Likely benign (Sep 24, 2022)
11-57659602-A-G			Benign (Jan 24, 2024)
11-57659627-C-A			Likely benign (Oct 03, 2023)
11-57659632-CAAG-C		Pontocerebellar hypoplasia type 10	Uncertain significance (Mar 27, 2018)
11-57659653-TG-CT			Uncertain significance (Dec 11, 2023)
11-57659654-G-T		Pontocerebellar hypoplasia type 10 • Inborn genetic diseases	Uncertain significance (May 11, 2022)
11-57659704-C-T			Likely benign (Jun 09, 2023)
11-57659705-G-A			Uncertain significance (Jun 29, 2022)
11-57659708-C-T			Uncertain significance (Oct 05, 2022)
11-57659760-A-G		Inborn genetic diseases	Uncertain significance (Aug 17, 2023)
11-57659769-C-G		Pontocerebellar hypoplasia type 10	Uncertain significance (Jul 18, 2019)
11-57659770-A-G			Likely benign (Dec 31, 2019)
11-57659786-C-G		Pontocerebellar hypoplasia type 10	Uncertain significance (Dec 28, 2019)
11-57659786-C-T			Uncertain significance (Sep 27, 2022)
11-57659796-C-T			Uncertain significance (Sep 12, 2022)
11-57659797-G-A		CLP1-related disorder	Likely benign (May 01, 2024)
11-57659823-G-A		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLP1	protein_coding	protein_coding	ENST00000533682	2	12876

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.203	0.795	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	152	253	0.601	0.0000154	2751
Missense in Polyphen		45	81.344	0.55321		825
Synonymous	1.36	77	93.7	0.822	0.00000475	919
Loss of Function	2.71	4	15.5	0.258	0.00000128	144

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000791	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Polynucleotide kinase that can phosphorylate the 5'- hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double-stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a key role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA (PubMed:24766809, PubMed:24766810). Its role in tRNA splicing and maturation is required for cerebellar development (PubMed:24766809, PubMed:24766810). Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing. {ECO:0000269|PubMed:17495927, ECO:0000269|PubMed:18648070, ECO:0000269|PubMed:24766809, ECO:0000269|PubMed:24766810}.
• Disease: DISEASE: Pontocerebellar hypoplasia 10 (PCH10) [MIM:615803]: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH10 features include cortical dysgenesis marked by a simplified gyral pattern, cortical atrophy, mild or focal cerebellar vermian volume loss, delayed myelination, progressive microcephaly, global growth and developmental delays, severe intellectual disabilities, and seizures refractory to treatment. {ECO:0000269|PubMed:24766809, ECO:0000269|PubMed:24766810}. Note=The disease is caused by mutations affecting the gene represented in this entry. Neurodegeneration is due to defects in tRNA splicing (PubMed:24766809, PubMed:24766810). {ECO:0000269|PubMed:24766809, ECO:0000269|PubMed:24766810}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);mRNA Processing;tRNA processing;Gene expression (Transcription);RNA Polymerase II Transcription;Metabolism of RNA;Processing of Intronless Pre-mRNAs;Processing of Capped Intronless Pre-mRNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;tRNA processing in the nucleus;mRNA Splicing;mRNA 3,-end processing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.295
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.824
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clp1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: clp1
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: broken

Gene ontology

• Biological process: mRNA splicing, via spliceosome;termination of RNA polymerase II transcription;mRNA polyadenylation;tRNA splicing, via endonucleolytic cleavage and ligation;phosphorylation;cerebellar cortex development;targeting of mRNA for destruction involved in RNA interference;mRNA 3'-end processing;siRNA loading onto RISC involved in RNA interference
• Cellular component: tRNA-intron endonuclease complex;nucleus;nucleoplasm;cytosol;mRNA cleavage factor complex
• Molecular function: ATP binding;ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity;polydeoxyribonucleotide kinase activity;ATP-dependent polyribonucleotide 5'-hydroxyl-kinase activity