LONP1

Chr 19

lon peptidase 1, mitochondrial

Also known as: CODASS, LON, LONP, LonHS, PIM1, PRSS15, hLON

NCBI Gene: 9361 ENSG00000196365 UniProt: P36776

This gene encodes an ATP-dependent serine protease in the mitochondrial matrix that degrades misfolded, damaged, or short-lived regulatory proteins and participates in mitochondrial gene expression regulation and genome maintenance. Biallelic mutations cause CODAS syndrome, an autosomal recessive disorder characterized by cerebral, ocular, dental, auricular, and skeletal abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.244), indicating that heterozygous loss-of-function mutations are likely not tolerated.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCODAS syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARLimitednot for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

108

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖