PGM3

Chr 6AR

phosphoglucomutase 3

Also known as: AGM1, IMD23, PAGM, PGM 3

NCBI Gene: 5238ENSG00000013375UniProt: O95394

This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Primary Disease Associations & Inheritance

Immunodeficiency 23MIM #615816
AR
578
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PGM3
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency 23 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 203 VUS of 578 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.65LOEUF
pLI 0.000
Z-score 3.12
OE 0.42 (0.28–0.65)
Tolerant

Typical tolerance to LoF variation

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.
1.51Z-score
OE missense 0.75 (0.68–0.84)
227 obs / 300.7 exp
Tolerant

Mild missense constraint

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.0.42 (0.28–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.68–0.84)
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.0.96
0≤1.21.6
LoF obs/exp: 14 / 33.5Missense obs/exp: 227 / 300.7Syn Z: 0.36

ClinVar Variant Classifications

578 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic18
VUS203
Likely Benign294
Benign7
Conflicting9
47
Pathogenic
18
Likely Pathogenic
203
VUS
294
Likely Benign
7
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
2
26
0
47
Likely Pathogenic
13
0
5
0
18
VUS
2
177
22
2
203
Likely Benign
0
9
127
158
294
Benign
0
1
3
3
7
Conflicting
—9
Total34189183163578

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

View in ClinVar →

Protein Context — Lollipop Plot

PGM3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PGM3-related immunodeficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency 23

MIM #615816

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PGM3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hyper IgE syndromes: clinical and molecular characteristics.
Al-Shaikhly T et al.·Immunol Cell Biol
2019Review
Liver glucose metabolism in humans.
Adeva-Andany MM et al.·Biosci Rep
2016Review
PGM3 insufficiency: a glycosylation disorder causing a notable T cell defect.
Yang L et al.·Front Immunol
2024
Hyper IgE Syndrome: Bridging the Gap Between Immunodeficiency, Atopy, and Allergic Diseases.
Sutanto H et al.·Curr Allergy Asthma Rep
2025Review
Hyper-IgE syndromes: reviewing PGM3 deficiency.
Yang L et al.·Curr Opin Pediatr
2014Review
ERBIN and phosphoglucomutase 3 deficiency.
Milner JD·Curr Opin Immunol
2023Review
Hyper-IgE Syndromes and the Lung.
Freeman AF et al.·Clin Chest Med
2016Review
Primary Immunodeficiencies with Elevated IgE.
Mogensen TH·Int Rev Immunol
2016Review
Human hyper-IgE syndrome: singular or plural?
Zhang Q et al.·Mamm Genome
2018Review
Hyper-IgE in the allergy clinic--when is it primary immunodeficiency?
Ponsford MJ et al.·Allergy
2018Review
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools