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.

not_provided (102 variants)
not_specified (43 variants)
CLPX-related_disorder (6 variants)
Protoporphyria,_erythropoietic,_2 (2 variants)

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. These statistics are base on transcript: NM_000006660.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				24 clinvar	6 clinvar	30
missense		1 clinvar	74 clinvar	7 clinvar	3 clinvar	85
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	74	31	9

Loading clinvar variants...

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
Phenotype

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