PGM2L1

Chr 11AR

phosphoglucomutase 2 like 1

Also known as: BM32A, NEDHFS, PMMLP

NCBI Gene: 283209ENSG00000165434UniProt: Q6PCE3

Enables glucose-1,6-bisphosphate synthase activity. Predicted to be involved in glucose metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesMIM #620191
AR
92
ClinVar variants
16
Pathogenic / LP
0.03
pLI score
1
Active trials
Clinical Summary— PGM2L1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 52 VUS of 92 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.50LOEUF
pLI 0.026
Z-score 3.72
OE 0.29 (0.17–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.24Z-score
OE missense 0.65 (0.58–0.73)
214 obs / 328.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.17–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.58–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 9 / 31.5Missense obs/exp: 214 / 328.2Syn Z: 1.14

ClinVar Variant Classifications

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS52
Likely Benign5
Benign19
16
Pathogenic
52
VUS
5
Likely Benign
19
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
11
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
49
3
0
52
Likely Benign
0
2
0
3
5
Benign
0
2
16
1
19
Total55330492

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PGM2L1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PGM2L1-related neurodevelopmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities

MIM #620191

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cancer-associated fibroblasts secrete CSF3 to promote TNBC progression via enhancing PGM2L1-dependent glycolysis reprogramming.
Qin W et al.·Cell Death Dis
2025
Identification of a Homozygous PGM2L1 Variant in a Male Patient With Developmental Delay and Seizures.
Niu M et al.·Mol Genet Genomic Med
2026Case report
Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder.
Morava E et al.·Am J Hum Genet
2021Case report
Delineating the Adult Phenotype of PGM2L1 -Related Neurodevelopmental Disorder.
Ercoskun P et al.·Am J Med Genet A
2026Case report
Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer.
Liu SS et al.·BMC Cancer
2024
Influence of smoking on colonic gene expression profile in Crohn's disease.
Nielsen OH et al.·PLoS One
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools