PGM5

Chr 9

phosphoglucomutase 5

Also known as: PGMRP

NCBI Gene: 5239ENSG00000154330UniProt: Q15124OMIM: 600981

PGM5 encodes a component of adherens-type cell-cell and cell-matrix junctions that positively regulates maturation and alignment of myofibrils and promotes sarcomere organization, despite its name suggesting phosphoglucomutase activity which it lacks in vitro. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 2S, characterized by progressive proximal muscle weakness. The gene shows tolerance to loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.66
Clinical Summary— PGM5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 98 VUS of 160 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.001
Z-score 2.88
OE 0.39 (0.24–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.80Z-score
OE missense 0.87 (0.79–0.96)
278 obs / 318.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.24–0.66)
0≤0.351.4
Missense OE0.87 (0.79–0.96)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 10 / 25.8Missense obs/exp: 278 / 318.0Syn Z: 0.40
DN
0.75top 25%
GOF
0.5170th %ile
LOF
0.2580th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic6
VUS98
Likely Benign5
Benign2
34
Pathogenic
6
Likely Pathogenic
98
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
6
0
6
VUS
0
94
4
0
98
Likely Benign
0
3
0
2
5
Benign
0
0
1
1
2
Total097453145

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

View in ClinVar →

Protein Context — Lollipop Plot

PGM5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients