PGM2L1

Chr 11AR

phosphoglucomutase 2 like 1

Also known as: BM32A, NEDHFS, PMMLP

NCBI Gene: 283209 ENSG00000165434 UniProt: Q6PCE3 OMIM: 611610

PGM2L1 encodes a glucose 1,6-bisphosphate synthase that uses 1,3-bisphosphoglycerate as a phosphate donor with various 1-phosphate sugars as acceptors in glucose metabolism. Mutations cause a neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities that follows autosomal recessive inheritance. The gene shows high constraint against loss-of-function variants (LOEUF 0.498), indicating intolerance to inactivating mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.501 OMIM phenotype

Clinical Summary— PGM2L1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 50 VUS of 100 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.29 (0.17–0.50)

0≤0.351.4

Missense OE?0.65 (0.58–0.73)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 9 / 31.5Missense obs/exp: 214 / 328.2Syn Z: 1.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPGM2L1-related neurodevelopmental disorderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6840th %ile

GOF

0.4776th %ile

LOF

0.2874th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic2

VUS50

Likely Benign5

Benign19

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	0	0	8
Likely Pathogenic	2	0	0	0	2
VUS	0	50	0	0	50
Likely Benign	0	2	0	3	5
Benign	0	2	16	1	19
Total	10	54	16	4	84

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap PGM2L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →