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.

• Multiple mitochondrial dysfunctions syndrome 6 (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.

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	12		13
missense	1	1	47	4	3	56
nonsense		2				2
start loss						0
frameshift		2	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region		1	3	8	3	15
non coding			29	10	10	49
Total	1	5	81	26	13

Highest pathogenic variant AF is 0.0000525

Variants in PMPCB

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

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

Position	Type	Phenotype	Significance	ClinVar
7-103297437-C-T			Benign (May 21, 2021)
7-103297453-A-G		PMPCB-related disorder	Likely benign (Apr 20, 2020)
7-103297457-G-T		Multiple mitochondrial dysfunctions syndrome 6 • PMPCB-related disorder	Uncertain significance (Oct 31, 2018)
7-103297464-C-T		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
7-103297467-C-T		PMPCB-related disorder • Inborn genetic diseases	Benign/Likely benign (Jan 17, 2024)
7-103297478-C-G		Multiple mitochondrial dysfunctions syndrome 6	Uncertain significance (Aug 09, 2023)
7-103297480-A-C			Likely benign (Dec 11, 2023)
7-103297487-T-G		Multiple mitochondrial dysfunctions syndrome 6 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 01, 2022)
7-103297491-C-A		Multiple mitochondrial dysfunctions syndrome 6	Likely pathogenic (Jun 05, 2020)
7-103297494-C-CCGCGG		PMPCB-related disorder	Uncertain significance (Feb 14, 2024)
7-103297673-C-T			Benign (Jan 01, 2023)
7-103298560-C-T			Benign/Likely benign (Jul 01, 2024)
7-103298572-T-C			Benign (Jan 26, 2024)
7-103298590-G-A		Multiple mitochondrial dysfunctions syndrome 6 • Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
7-103298604-C-A		Inborn genetic diseases • Multiple mitochondrial dysfunctions syndrome 6	Uncertain significance (Aug 09, 2023)
7-103298618-A-C		Multiple mitochondrial dysfunctions syndrome 6	Uncertain significance (Jul 21, 2019)
7-103298633-T-A			Likely benign (Dec 22, 2022)
7-103298648-A-G		PMPCB-related disorder	Likely benign (Jul 11, 2019)
7-103298689-C-G			Uncertain significance (Mar 18, 2023)
7-103298697-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
7-103299436-C-G		PMPCB-related disorder	Likely benign (Mar 23, 2020)
7-103299437-A-G			Likely benign (Jun 13, 2022)
7-103299440-A-G			Benign (Jan 29, 2024)
7-103299492-A-G		See cases	Uncertain significance (Oct 22, 2021)
7-103299505-C-T		PMPCB-related disorder	Likely benign (Aug 23, 2022)

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