PMPCB

peptidase, mitochondrial processing subunit beta, the group of M16 metallopeptidases

Basic information

Region (hg38): 7:103297407-103331818

Links

ENSG00000105819

∙ NCBI:9512 ∙ OMIM:603131 ∙ HGNC:9119 ∙ Uniprot:O75439 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

multiple mitochondrial dysfunctions syndrome 6 (Moderate), mode of inheritance: AR
multiple mitochondrial dysfunctions syndrome 6 (Strong), mode of inheritance: AR
multiple mitochondrial dysfunctions syndrome 6 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple mitochondrial dysfunctions syndrome 6	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	Biochemical	29576218

ClinVar

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

not_provided (81 variants)
Inborn_genetic_diseases (64 variants)
Multiple_mitochondrial_dysfunctions_syndrome_6 (24 variants)
PMPCB-related_disorder (17 variants)
PMPCB-related_mitochondrial_disorder (1 variants)
PMPCB-related_ataxia (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMPCB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004279.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	18 clinvar	2 clinvar	22
missense	3 clinvar	2 clinvar	75 clinvar	10 clinvar	2 clinvar	92
nonsense		2 clinvar				2
start loss						0
frameshift		2 clinvar	3 clinvar			5
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	6	81	28	4

Highest pathogenic variant AF is 0.00007683338

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMPCB	protein_coding	protein_coding	ENST00000249269	13	32090

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.53e-8	0.953	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.216	279	269	1.04	0.0000135	3173
Missense in Polyphen		76	67.687	1.1228		815
Synonymous	-0.245	93	90.0	1.03	0.00000433	952
Loss of Function	1.96	16	27.0	0.592	0.00000139	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000539	0.000537
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000221	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000221	0.000217
South Asian	0.000310	0.000294
Other	0.000356	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins (PubMed:29576218). Most MPP cleavage sites follow an arginine at position -2 (By similarity). {ECO:0000250|UniProtKB:P20069, ECO:0000269|PubMed:29576218}.;
Disease: DISEASE: Multiple mitochondrial dysfunctions syndrome 6 (MMDS6) [MIM:617954]: An autosomal recessive, neurodegenerative disorder characterized by basal ganglia lesions, cerebellar atrophy, and neurologic regression in the first year of life. Common features include truncal hypotonia, lack of independent ambulation, poor speech, intellectual disability, and motor abnormalities, such as ataxia, dystonia, and spasticity. {ECO:0000269|PubMed:29576218}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Metabolism of proteins;Transport of small molecules;Mitochondrial protein import;Mitochondrial calcium ion transport;Processing of SMDT1 (Consensus)

Recessive Scores

pRec: 0.106

Intolerance Scores

loftool: 0.878
rvis_EVS: -0.42
rvis_percentile_EVS: 25.73

Haploinsufficiency Scores

pHI: 0.237
hipred: Y
hipred_score: 0.545
ghis: 0.609

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.631

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pmpcb
Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: protein processing involved in protein targeting to mitochondrion;mitochondrial calcium ion transmembrane transport
Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial processing peptidase complex
Molecular function: endopeptidase activity;metalloendopeptidase activity;metal ion binding