LONP2
protein-codinglon peptidase 2, peroxisomal, the group of AAA ATPases
Gene summary
In human, peroxisomes function primarily to catalyze fatty acid beta-oxidation and, as a by-product, produce hydrogen peroxide and superoxide. The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome homeostasis as well as proteolytically degrading peroxisomal proteins damaged by oxidation. The protein has an N-terminal Lon N substrate recognition domain, an ATPase domain, a proteolytic domain, and, in some isoforms, a C-terminal peroxisome targeting sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~118.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LONP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031490.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 73 | 2 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 73 | 3 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_113678.2 | 15 | MANE Select | |
| Ensembl | ENSP00000285737.4 | 15 | MANE Select | |
| RefSeq | NP_001287877.1 | 14 | Standard | |
| RefSeq | NP_001335007.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of proteins
- Chaperonin-mediated protein folding
- Association of TriC/CCT with target proteins during biosynthesis
- Peroxisomal protein import
- Protein folding
Biological Process
- protein quality control for misfolded or incompletely synthesized proteins
- protein targeting to peroxisome
- peroxisome organization
- response to organic cyclic compound
- protein processing
Molecular Function
- protease binding
- ATP-dependent peptidase activity
- serine-type endopeptidase activity
- signaling receptor binding
- protein binding
Cellular Component
- nucleus
- peroxisome
- peroxisomal matrix
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000285737
- Coding exons
- 15
- Length
- 118827
- Individuals with no LoFs
- 125495
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 253
- Defined
- 125748
- p
- 0.00101
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.23 | 337 | 474 | 0.711 | 0.0000252 | 5530 |
| Missense (PolyPhen) | 119 | 197.98 | 0.60108 | 2195 | ||
| Synonymous | 1.12 | 153 | 172 | 0.891 | 0.00000885 | 1728 |
| Loss of Function | -0.233 | 41 | 39.4 | 1.04 | 0.00000232 | 457 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.0015 | 0.0015 | notable |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.0013 | 0.0013 | notable |
| South Asian | 0.00097 | 0.00091 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import (By similarity). May indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1. {ECO:0000255|HAMAP- Rule:MF_03121, ECO:0000269|PubMed:22002062}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.868
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.875
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |