GeneBe

PMPCA

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

Basic information

Region (hg38): 9:136410630-136427992

Previous symbols: [ "INPP5E", "SCAR2", "CLA1" ]

Links

ENSG00000165688 ∙ NCBI:23203 ∙ OMIM:613036 ∙ HGNC:18667 ∙ Uniprot:Q10713 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • autosomal recessive spinocerebellar ataxia 2 (Moderate), mode of inheritance: AR
  • autosomal recessive spinocerebellar ataxia 2 (Supportive), mode of inheritance: AR
  • autosomal recessive spinocerebellar ataxia 2 (Strong), mode of inheritance: AR
  • mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spinocerebellar ataxia, autosomal recessive 2ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic10528257; 25808372; 26657514

ClinVar

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

  • not_provided (132 variants)
  • Inborn_genetic_diseases (82 variants)
  • Autosomal_recessive_spinocerebellar_ataxia_2 (23 variants)
  • PMPCA-related_disorder (7 variants)
  • Chronic_lactic_acidosis (2 variants)
  • Normal_pressure_hydrocephalus (2 variants)
  • Hypertrophic_cardiomyopathy (2 variants)
  • Optic_atrophy (2 variants)
  • Diffuse_cerebellar_atrophy (2 variants)
  • Severe_global_developmental_delay (2 variants)
  • Bilateral_ptosis (2 variants)
  • Hypoventilation (2 variants)
  • not_specified (2 variants)
  • Blindness (2 variants)
  • Restrictive_external_ophthalmoplegia (2 variants)
  • Global_brain_atrophy (2 variants)
  • Failure_to_thrive (2 variants)
  • Floppy_infant (2 variants)
  • Cerebellar_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMPCA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015160.3. 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.

EffectPLPVUSLBBSum
synonymous
47
clinvar
1
clinvar
 48
missense
6
clinvar
1
clinvar
118
clinvar
6
clinvar
1
clinvar
 132
nonsense
2
clinvar
 2
start loss
0
frameshift
2
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total 9 5 118 53 2

Highest pathogenic variant AF is 0.00008861469

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PMPCAprotein_codingprotein_codingENST00000371717 1313104
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
3.44e-110.5021257010471257480.000187
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.1623243320.9750.00002113383
Missense in Polyphen83103.240.803921070
Synonymous-1.311641441.140.00001041070
Loss of Function1.272027.20.7360.00000157297

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003270.000326
Ashkenazi Jewish0.001190.00119
East Asian0.0002720.000272
Finnish0.0001390.000139
European (Non-Finnish)0.0001070.000105
Middle Eastern0.0002720.000272
South Asian0.0001650.000163
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins (PubMed:25808372). Most MPP cleavage sites follow an arginine at position -2 (By similarity). {ECO:0000250|UniProtKB:P20069, ECO:0000269|PubMed:25808372}.;
Disease
DISEASE: Spinocerebellar ataxia, autosomal recessive, 2 (SCAR2) [MIM:213200]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Additional features often include loss of fine motor skills, dysarthria, nystagmus, cerebellar signs, and delayed cognitive development with intellectual disability. {ECO:0000269|PubMed:25808372, ECO:0000269|PubMed:26657514}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Metabolism of proteins;3-phosphoinositide degradation;Transport of small molecules;Mitochondrial protein import;Mitochondrial calcium ion transport;Processing of SMDT1 (Consensus)

Recessive Scores

pRec
0.107

Intolerance Scores

loftool
0.692
rvis_EVS
-1.18
rvis_percentile_EVS
5.97

Haploinsufficiency Scores

pHI
0.296
hipred
N
hipred_score
0.476
ghis
0.615

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.733

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pmpca
Phenotype

Gene ontology

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