LONP1

lon peptidase 1, mitochondrial, the group of Serine proteases|AAA ATPases

Basic information

Region (hg38): 19:5691833-5720572

Previous symbols: [ "PRSS15" ]

Links

ENSG00000196365 ∙ NCBI:9361 ∙ OMIM:605490 ∙ HGNC:9479 ∙ Uniprot:P36776 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CODAS syndrome (Strong), mode of inheritance: AR
• CODAS syndrome (Strong), mode of inheritance: AR
• CODAS syndrome (Supportive), mode of inheritance: AR
• pyruvate dehydrogenase E1-alpha deficiency (Supportive), mode of inheritance: XL
• CODAS syndrome (Strong), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	25574826

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LONP1 gene.

• not provided (699 variants)
• Inborn genetic diseases (67 variants)
• CODAS syndrome (23 variants)
• not specified (5 variants)
• LONP1-related condition (4 variants)
• LONP1-related disorders (2 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• Intellectual disability;Short stature;Ventricular septal defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LONP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	188	25	215
missense		4	224	52	11	291
nonsense		1				1
start loss						0
frameshift	2	3	1			6
inframe indel			6	1		7
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region			13	21	9	43
non coding			3	99	33	135
Total	3	9	237	340	69

Variants in LONP1

This is a list of pathogenic ClinVar variants found in the LONP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-5691922-G-A			Likely benign (Sep 29, 2018)
19-5691976-T-TCAGTTCTGGCCCAGACAGGGCCTGACATC			Benign (Aug 03, 2018)
19-5692033-C-T			Likely benign (Dec 20, 2021)
19-5692035-C-G			Likely benign (Oct 29, 2021)
19-5692035-C-T			Likely benign (Jan 04, 2024)
19-5692037-G-A			Uncertain significance (Jul 17, 2023)
19-5692043-C-T			Uncertain significance (May 11, 2022)
19-5692044-G-A			Likely benign (Jun 07, 2023)
19-5692050-C-G			Likely benign (Jul 19, 2023)
19-5692050-C-T			Likely benign (Jul 29, 2023)
19-5692052-C-A			Uncertain significance (Sep 26, 2022)
19-5692057-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 11, 2024)
19-5692059-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 17, 2023)
19-5692062-C-A			Likely benign (Jan 07, 2024)
19-5692062-C-T			Likely benign (Jan 03, 2023)
19-5692065-G-C			Uncertain significance (Aug 31, 2022)
19-5692065-G-T			Likely benign (Aug 19, 2022)
19-5692068-C-T			Likely benign (Jul 21, 2023)
19-5692069-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
19-5692069-G-C			Uncertain significance (Jul 06, 2022)
19-5692070-G-A			Uncertain significance (Jan 25, 2022)
19-5692074-G-T			Likely benign (Nov 01, 2022)
19-5692076-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 30, 2024)
19-5692077-G-A			Likely benign (Sep 14, 2023)
19-5692077-G-C			Uncertain significance (Nov 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LONP1	protein_coding	protein_coding	ENST00000360614	18	28739

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000701	125736	0	8	125744	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.428	605	635	0.952	0.0000431	6172
Missense in Polyphen		178	242.17	0.73504		2277
Synonymous	-4.80	404	298	1.35	0.0000229	1982
Loss of Function	5.37	5	43.0	0.116	0.00000210	493

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000363	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single- stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site- specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters (PubMed:12198491, PubMed:15870080, PubMed:17420247, PubMed:8248235). Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, helicase Twinkle (TWNK) and the large ribosomal subunit protein bL32m. bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575). {ECO:0000255|HAMAP-Rule:MF_03120, ECO:0000269|PubMed:12198491, ECO:0000269|PubMed:15870080, ECO:0000269|PubMed:17420247, ECO:0000269|PubMed:17579211, ECO:0000269|PubMed:28377575, ECO:0000269|PubMed:8248235}.
• Disease: DISEASE: CODAS syndrome (CODASS) [MIM:600373]: A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts. {ECO:0000269|PubMed:25574826, ECO:0000269|PubMed:25808063}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.425

Intolerance Scores

• loftool: 0.135
• rvis_EVS: -1.82
• rvis_percentile_EVS: 2.14

Haploinsufficiency Scores

• pHI: 0.251
• hipred: Y
• hipred_score: 0.662
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lonp1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: mitochondrial genome maintenance;response to hypoxia;protein quality control for misfolded or incompletely synthesized proteins;mitochondrion organization;aging;response to hormone;response to aluminum ion;mitochondrial DNA metabolic process;cellular response to oxidative stress;chaperone-mediated protein complex assembly;protein homooligomerization;proteolysis involved in cellular protein catabolic process;oxidation-dependent protein catabolic process
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;cytosol;membrane;mitochondrial nucleoid
• Molecular function: mitochondrial promoter sequence-specific DNA binding;single-stranded DNA binding;single-stranded RNA binding;ATP-dependent peptidase activity;serine-type endopeptidase activity;protein binding;ATP binding;ADP binding;sequence-specific DNA binding;G-quadruplex DNA binding;DNA polymerase binding