CLPX

caseinolytic mitochondrial matrix peptidase chaperone subunit X, the group of AAA ATPases

Basic information

Region (hg38): 15:65148219-65185342

Links

ENSG00000166855 ∙ NCBI:10845 ∙ OMIM:615611 ∙ HGNC:2088 ∙ Uniprot:O76031 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• protoporphyria, erythropoietic, 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Protoporphyria, erythropoietic, 2	AD	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	Dermatologic	28874591

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLPX 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				19	4	23
missense		1	47	4	3	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	3		5
non coding			1	9	3	13
Total	0	1	48	32	10

Variants in CLPX

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

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

Position	Type	Phenotype	Significance	ClinVar
15-65150817-G-A		CLPX-related disorder	Likely benign (Sep 10, 2019)
15-65150834-C-T		not specified	Uncertain significance (Jan 23, 2024)
15-65150857-C-T		not specified	Uncertain significance (Sep 22, 2022)
15-65150871-T-A			Likely benign (Jan 23, 2023)
15-65150884-T-C		not specified	Uncertain significance (Feb 06, 2023)
15-65150929-A-G			Likely benign (Jan 22, 2024)
15-65150930-T-C			Likely benign (Jul 29, 2023)
15-65152453-T-C			Likely benign (Aug 16, 2022)
15-65152478-T-A			Benign (Oct 14, 2022)
15-65152494-C-G		not specified	Uncertain significance (Jan 19, 2024)
15-65153556-C-A			Benign (Aug 16, 2023)
15-65153599-G-T			Uncertain significance (Jul 09, 2023)
15-65153636-C-T		not specified	Uncertain significance (Jun 03, 2024)
15-65153647-T-C			Likely benign (Apr 08, 2022)
15-65154763-C-T			Likely benign (Feb 06, 2022)
15-65154802-C-T		not specified	Uncertain significance (Dec 07, 2021)
15-65154806-G-A			Likely benign (Sep 06, 2023)
15-65154908-C-T			Likely benign (Aug 09, 2023)
15-65154930-A-G			Conflicting classifications of pathogenicity (Jan 06, 2024)
15-65154940-T-C		not specified	Uncertain significance (Nov 23, 2021)
15-65154950-A-G			Benign (Jan 13, 2024)
15-65154955-G-A		not specified	Uncertain significance (Dec 14, 2023)
15-65154963-C-T			Uncertain significance (Mar 14, 2022)
15-65154964-G-A			Uncertain significance (Aug 09, 2023)
15-65154969-T-C			Uncertain significance (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLPX	protein_coding	protein_coding	ENST00000300107	14	37124

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.924	0.0762	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.81	242	336	0.721	0.0000171	4054
Missense in Polyphen		68	142.13	0.47842		1718
Synonymous	0.346	115	120	0.960	0.00000565	1262
Loss of Function	4.51	6	34.7	0.173	0.00000201	423

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000125	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000718	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP. Targets specific substrates for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:22841477). ATP- dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis. Important for efficient erythropoiesis through upregulation of heme biosynthesis (PubMed:25957689). {ECO:0000269|PubMed:11923310, ECO:0000269|PubMed:22710082, ECO:0000269|PubMed:22841477, ECO:0000269|PubMed:25957689}.

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.515
• rvis_EVS: -0.25
• rvis_percentile_EVS: 36.07

Haploinsufficiency Scores

• pHI: 0.486
• hipred: Y
• hipred_score: 0.718
• ghis: 0.609

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0915

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clpx

Zebrafish Information Network

• Gene name: clpxa
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein folding;positive regulation of peptidase activity;protein catabolic process;ATP metabolic process;proteolysis involved in cellular protein catabolic process
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial matrix;cytosol;endopeptidase Clp complex;mitochondrial endopeptidase Clp complex;mitochondrial nucleoid
• Molecular function: ATP-dependent peptidase activity;protein binding;ATP binding;peptidase activator activity;ATPase activity;metal ion binding;unfolded protein binding