PITRM1

Chr 10AR

pitrilysin metallopeptidase 1

Also known as: MP1, PreP, SCAR30

NCBI Gene: 10531ENSG00000107959UniProt: Q5JRX3OMIM: 618211

This gene encodes a mitochondrial matrix metalloendopeptidase that degrades transit peptides after mitochondrial protein import and can also degrade amyloid-beta peptides that accumulate in mitochondria. Mutations cause spinocerebellar ataxia, autosomal recessive 30, which follows autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern of the associated ataxia.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.941 OMIM phenotype
Clinical Summary— PITRM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 221 VUS of 400 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.93
OE 0.72 (0.56–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.84Z-score
OE missense 1.10 (1.03–1.17)
653 obs / 595.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.72 (0.56–0.94)
0≤0.351.4
Missense OE1.10 (1.03–1.17)
0≤0.61.4
Synonymous OE1.22
0≤1.21.6
LoF obs/exp: 40 / 55.5Missense obs/exp: 653 / 595.5Syn Z: -2.68

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS221
Likely Benign106
Benign9
Conflicting7
2
Pathogenic
1
Likely Pathogenic
221
VUS
106
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
1
0
0
0
1
VUS
4
209
8
0
221
Likely Benign
0
20
29
57
106
Benign
0
0
7
2
9
Conflicting
—7
Total52294659346

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PITRM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PPAR-gamma agonist pioglitazone recovers mitochondrial quality control in fibroblasts from PITRM1-deficient patients.
Di Donfrancesco A et al.·Front Pharmacol
2023Open AccessCohort
In silico exploration of antioxidants as oxidation protectant for PITRM1 peptidase activity, an Alzheimer disease target.
Wilson Alphonse CR et al.·J Cell Biochem
2023
PITRM1 interaction studies with amyloidogenic nonapeptide mutants of familial Alzheimer's disease.
Wilson Alphonse CR et al.·J Biomol Struct Dyn
2023
Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration.
Brunetti D et al.·Biomedicines
2021Open Access
Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer's disease.
Du F et al.·Aging Cell
2021Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients