Severe early-onset obesity

Gene: PGM2L1

Amber List (moderate evidence)

PGM2L1 (phosphoglucomutase 2 like 1)
EnsemblGeneIds (GRCh38): ENSG00000165434
EnsemblGeneIds (GRCh37): ENSG00000165434
OMIM: 611610, Gene2Phenotype
PGM2L1 is in 3 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update (tagged).

Morava et al. 2021 (PMID: 33979636) identified 4 unrelated individuals with different biallelic protein-truncating variants in the PGM2L1 gene. All had severe GDD/ID. Other features that reach the threshold for inclusion on the relevant panels (observed in at least 3 cases) are epilepsy and early obesity (99th centile at ages 2 to 3). Some functional data included.
Created: 12 Aug 2021, 3:42 p.m. | Last Modified: 12 Aug 2021, 3:42 p.m.
Panel Version: 3.1218

Zornitza Stark (Australian Genomics)

Green List (high evidence)

PMID: 33979636:
- Bi-allelic PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Sources: Literature
Created: 12 Jun 2021, 3:14 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Neurodevelopmental disorder



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Literature
  • Expert Review Amber
  • Neurodevelopmental disorder
Q3_21_rating gene-checked
Clinvar variants
Variants in PGM2L1
Panels with this gene

History Filter Activity

10 May 2022, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: PGM2L1.

12 Aug 2021, Gel status: 2

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

Arina Puzriakova (Genomics England Curator)

gene: PGM2L1 was added gene: PGM2L1 was added to Severe early-onset obesity. Sources: Expert Review Amber,Literature Q3_21_rating tags were added to gene: PGM2L1. Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PGM2L1 were set to 33979636 Phenotypes for gene: PGM2L1 were set to Neurodevelopmental disorder