Pyruvate dehydrogenase (PDH) deficiency

Gene: LONP1

Green List (high evidence)

LONP1 (lon peptidase 1, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000196365
EnsemblGeneIds (GRCh37): ENSG00000196365
OMIM: 605490, Gene2Phenotype
LONP1 is in 11 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

PMID:40931319 (2026) reported 16 individuals with 16 different variants in LONP1 gene, of which 11 individuals are new patients with neurodevelopmental features without congenital diaphragmatic hernia (CDH) or classic cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS features), and five are previously reported cases. Seven of these patients are identified with heterozygous variants, while the rest are identified with either homozygous or compound heterozygous variants. Of seven patients with monoallelic variants, only one patient had biochemically confirmed PDH deficiency. Among nine patients with biallelic variants, two patients had PDH deficiency.

Biallelic variants are associated with relevant phenotypes in OMIM (MIM #600373, last accessed 23 July 2026) and in Gene2Phenotype ('strong' rating on DD, Eye and Skeletal panels). Monoallelic variants are not yet associated with relevant phenotypes in OMIM.
Created: 14 Aug 2026, 2:38 p.m. | Last Modified: 14 Aug 2026, 2:38 p.m.
Panel Version: 1.42

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CODAS syndrome, OMIM:600373; CODAS syndrome, MONDO:0010879; neurodevelopmental disorder, MONDO:0700092

Publications

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group. Gene Symbol submitted: LONP1; Suggested intial gene rating: Green; Information provided: Mode of inheritance, phenotype and publication.
Created: 1 Feb 2019, 2:42 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CODAS syndrome, 600373

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Mutations in the gene have been reported in more than 3 unrelated cases of CODAS syndrome in two independent publications, and functional studies support a role in the disease. It is a probable DD gene for CODAS syndrome.
Created: 15 Feb 2016, 3:11 p.m.

Shamima Rahman (UCL Institute of Child Health)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
Phenotypes
  • CODAS syndrome, OMIM:600373
  • CODAS syndrome, MONDO:0010879
  • neurodevelopmental disorder, MONDO:0700092
OMIM
605490
Clinvar variants
Variants in LONP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Aug 2026, Gel status: 3

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: LONP1 were changed from CODAS syndrome OMIM:600373; CODAS syndrome MONDO:0010879 to CODAS syndrome, OMIM:600373; CODAS syndrome, MONDO:0010879; neurodevelopmental disorder, MONDO:0700092

14 Aug 2026, Gel status: 3

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: LONP1 were set to 30304514

17 Mar 2021, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: LONP1 were changed from CODAS syndrome, 600373 to CODAS syndrome OMIM:600373; CODAS syndrome MONDO:0010879

1 Feb 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ivone Leong (Genomics England Curator)

gene: LONP1 was added gene: LONP1 was added to Pyruvate dehydrogenase (PDH) deficiency. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: LONP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LONP1 were set to 30304514 Phenotypes for gene: LONP1 were set to CODAS syndrome, 600373