PITRM1

Chr 10AR

pitrilysin metallopeptidase 1

Also known as: MP1, PreP, SCAR30

NCBI Gene: 10531ENSG00000107959UniProt: Q5JRX3

The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 30MIM #619405
AR
554
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PITRM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 193 VUS of 554 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.93
OE 0.72 (0.56–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.84Z-score
OE missense 1.10 (1.03–1.17)
653 obs / 595.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.56–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.03–1.17)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 40 / 55.5Missense obs/exp: 653 / 595.5Syn Z: -2.68

ClinVar Variant Classifications

554 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic2
VUS193
Likely Benign108
Benign53
Conflicting15
27
Pathogenic
2
Likely Pathogenic
193
VUS
108
Likely Benign
53
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
24
0
27
Likely Pathogenic
0
0
2
0
2
VUS
3
176
14
0
193
Likely Benign
0
16
35
57
108
Benign
0
20
19
14
53
Conflicting
—15
Total42149471398

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia, autosomal recessive 30

MIM #619405

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch 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
2023🔓 Open 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
2021🔓 Open 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
2021🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Arrhythmogenic Right Ventricular Dysplasia

Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD

RECRUITING
NCT03593317Phase PHASE2Hospices Civils de LyonStarted 2024-12-20
SpironolactonePlacebo

External Resources

Links to major genomics databases and tools