PGAM2
protein-codingphosphoglycerate mutase 2, the group of Phosphoglycerate mutases|Bisphosphoglycerate phosphatases
Gene summary
Phosphoglycerate mutase (PGAM) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. The PGAM is a dimeric enzyme containing, in different tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). This gene encodes muscle-specific PGAM subunit. Mutations in this gene cause muscle phosphoglycerate mutase eficiency, also known as glycogen storage disease X. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009865
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0009865
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009865
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Musculoskeletal; Renal
Intervention: Renal
Rationale: Preventive measures to reduce the chance of severe sequelae can be beneficial, as individuals can present with exercise intolerance, and renal failure has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PGAM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000290.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 48 | 3 | 51 | |||
| missense | 2 | 102 | 5 | 1 | 110 | |
| nonsense | 5 | 1 | 1 | 7 | ||
| start loss | 0 | |||||
| frameshift | 3 | 2 | 5 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 8 | 5 | 104 | 53 | 4 | 174 |
Highest pathogenic variant AF is 0.00038297178
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000281.2 | 3 | MANE Select | |
| Ensembl | ENSP00000297283.3 | 3 | MANE Select | |
| Ensembl | ENSP00000641419.1 | 3 | Standard | |
| Ensembl | ENSP00000641419.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pgam2 | Danio rerio | Structure: fast muscle cell Quality: decreased diameter abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Central carbon metabolism in cancer - Homo sapiens (human)
- Glucagon signaling pathway - Homo sapiens (human)
- Glycine, serine and threonine metabolism - Homo sapiens (human)
- Warburg Effect
Biological Process
- gluconeogenesis
- glycolytic process
- striated muscle contraction
- Notch signaling pathway
- spermatogenesis
Molecular Function
- bisphosphoglycerate mutase activity
- phosphoglycerate mutase activity
- hydrolase activity
- 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase activity
- cofactor binding
Cellular Component
- nucleus
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297283
- Coding exons
- 3
- Length
- 2861
- Individuals with no LoFs
- 125574
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 172
- Defined
- 125747
- p
- 0.000688
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.667 | 180 | 157 | 1.15 | 0.0000105 | 1647 |
| Missense (PolyPhen) | 78 | 68.633 | 1.1365 | 705 | ||
| Synonymous | -0.651 | 70 | 63.4 | 1.10 | 0.00000432 | 500 |
| Loss of Function | -0.287 | 10 | 9.07 | 1.10 | 3.97e-7 | 106 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0075 | 0.0075 | notable |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00020 | 0.00020 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interconversion of 3- and 2-phosphoglycerate with 2,3- bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity.;
Recessive Scores
- pRec
- 0.215
Intolerance Scores
- LoFtool
- 0.468
- RVIS EVS
- -0.51
- RVIS percentile EVS
- 21.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |