IMMP2L

Chr 7

inner mitochondrial membrane peptidase subunit 2

Also known as: IMMP2L-IT1, IMP2, IMP2-LIKE

NCBI Gene: 83943ENSG00000184903UniProt: Q96T52

This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

Primary Disease Associations & Inheritance

UniProtGilles de la Tourette syndrome
183
ClinVar variants
22
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— IMMP2L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 144 VUS of 183 total submissions

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.
1.20LOEUF
pLI 0.011
Z-score 1.21
OE 0.53 (0.26–1.20)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.17Z-score
OE missense 0.95 (0.81–1.13)
96 obs / 100.9 exp
Tolerant

Mild missense constraint

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.0.53 (0.26–1.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.81–1.13)
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.1.08
0≤1.21.6
LoF obs/exp: 4 / 7.6Missense obs/exp: 96 / 100.9Syn Z: -0.38

ClinVar Variant Classifications

183 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS144
Likely Benign8
Benign9
20
Pathogenic
2
Likely Pathogenic
144
VUS
8
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
111
33
0
144
Likely Benign
0
3
5
0
8
Benign
0
2
2
5
9
Total0116625183

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

View in ClinVar →

Protein Context — Lollipop Plot

IMMP2L · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial-related genome-wide Mendelian randomization identifies putatively causal genes in the pathogenesis of sepsis.
Sun J et al.·Surgery
2025Review
Transcriptional response to mitochondrial protease IMMP2L knockdown in human primary astrocytes.
Gokoolparsadh A et al.·Biochem Biophys Res Commun
2017
Identification of methylation markers for diagnosis of autism spectrum disorder.
Zhang B et al.·Metab Brain Dis
2022
The genetics of autism.
Muhle R et al.·Pediatrics
2004Review
Replication of SNP associations with keratoconus in a Czech cohort.
Liskova P et al.·PLoS One
2017Cohort
Mapping the landscape of childhood obesity: genomic insights and socioeconomic status in Indian school-going children.
Nair JM et al.·Obesity (Silver Spring)
2025
Identification of genetic association between mitochondrial dysfunction and knee osteoarthritis through integrating multi-omics: a summary data-based Mendelian randomization study.
Xie J et al.·Clin Rheumatol
2024
Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome.
Petek E et al.·Am J Hum Genet
2001Case report
Genome-wide association study on differentiated thyroid cancer.
Köhler A et al.·J Clin Endocrinol Metab
2013
Non-random inactivation of large common fragile site genes in different cancers.
McAvoy S et al.·Cytogenet Genome Res
2007Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Immp2l gene knockout induces granulosa cell senescence by activation of cGAS-STING pathway via TFAM-mediated mtDNA leakage.
Pan P et al.·Int J Biol Macromol
2025
Immp2l Deficiency Induced Granulosa Cell Senescence Through STAT1/ATF4 Mediated UPRmt and STAT1/(ATF4)/HIF1α/BNIP3 Mediated Mitophagy: Prevented by Enocyanin.
Qu X et al.·Int J Mol Sci
2024🔓 Open Access
Immp2l Enhances the Structure and Function of Mitochondrial Gpd2 Dehydrogenase.
Clarke RA et al.·Int J Mol Sci
2024🔓 Open Access
Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse.
Lawther AJ et al.·Genes (Basel)
2023🔓 Open AccessFunctional
Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder.
Leung BK et al.·Behav Brain Res
2023Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools