CLPB

ClpB family mitochondrial disaggregase, the group of Chaperonins|AAA ATPases|Ankyrin repeat domain containing

Basic information

Region (hg38): 11:72285495-72434680

Links

ENSG00000162129 ∙ NCBI:81570 ∙ OMIM:616254 ∙ HGNC:30664 ∙ Uniprot:Q9H078 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria, type VIIB (Definitive), mode of inheritance: AR
• 3-methylglutaconic aciduria, type VIIB (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria, type VIIB (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria, type VIIB (Supportive), mode of inheritance: AR
• neutropenia, severe congenital, 9, autosomal dominant (Strong), mode of inheritance: AD
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 9, autosomal dominant; 3-methylglutaconic aciduria, type VIIA, autosomal dominant; 3-methylglutaconic aciduria, type VIIB, autosomal recessive	AD/AR	Allergy/Immunology/Infectious; Oncologic	3-methylglutaconic aciduria can involve neutropenia, with recurrent/severe infections in some, and awareness may allow early and aggressive management of infections; Indidivuals with 3-methylglutaconic aciduria, type VIIB have been reported with leukemia, and awareness may allow early diagnosis and management; HSCT has been described in 3-methylglutaconic aciduria, type VIIA; Neutropenia, severe congenital, 9 may involve many of the features of 3-methylglutaconic aciduria, including increased risk of infections and certain types of cancer, and awareness may allow early diagnosis and management	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Endocrine; Hematologic; Neurologic; Oncologic; Ophthalmologic	25597510; 25597511; 25650066; 34115842; 34140661

ClinVar

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

• 3-methylglutaconic_aciduria,_type_VIIB (640 variants)
• not_provided (170 variants)
• Inborn_genetic_diseases (88 variants)
• CLPB-related_disorder (34 variants)
• not_specified (29 variants)
• Neutropenia,_severe_congenital,_9,_autosomal_dominant (15 variants)
• 3-methylglutaconic_aciduria,_type_VIIA (12 variants)
• Decreased_total_neutrophil_count (2 variants)
• Premature_ovarian_insufficiency (2 variants)
• 3-Methylglutaconic_aciduria (1 variants)
• Myeloid_maturation_arrest (1 variants)
• 3-Methylglutaric_aciduria (1 variants)
• Neutropenia,_severe_congenital,_2,_autosomal_dominant (1 variants)
• Microcytic_anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLPB gene is commonly pathogenic or not. These statistics are base on transcript: NM_001258392.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	137	3	144
missense	10	8	341	23	2	384
nonsense	9	3				12
start loss			1			1
frameshift	7	1	4			12
splice donor/acceptor (+/-2bp)		10	1			11
Total	26	22	351	160	5

Highest pathogenic variant AF is 0.000197645

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLPB	protein_coding	protein_coding	ENST00000294053	17	142224

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000499	0.999	125631	0	117	125748	0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	378	440	0.859	0.0000261	4588
Missense in Polyphen		91	154.87	0.58759		1619
Synonymous	1.21	156	176	0.885	0.0000103	1440
Loss of Function	3.81	13	38.5	0.337	0.00000207	412

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000721	0.000720
Ashkenazi Jewish	0.00	0.00
East Asian	0.00397	0.00398
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00397	0.00398
South Asian	0.000163	0.000163
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a regulatory ATPase and be related to secretion/protein trafficking process.
• Pathway: Longevity regulating pathway - multiple species - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.804
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.62

Haploinsufficiency Scores

• pHI: 0.132
• hipred: Y
• hipred_score: 0.578
• ghis: 0.481

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.950

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clpb

Zebrafish Information Network

• Gene name: clpb
• Affected structure: glycinergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cellular response to heat
• Cellular component: cellular_component;mitochondrion
• Molecular function: molecular_function;protein binding;ATP binding;ATPase activity