PGAM5
protein-codingPGAM family member 5, mitochondrial serine/threonine protein phosphatase, the group of Phosphoglycerate mutases|Serine/threonine phosphatases
Gene summary
Enables protein serine/threonine phosphatase activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and positive regulation of mitochondrial fission. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PGAM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001170543.2. 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 | 1 | 2 | 3 | |||
| missense | 50 | 50 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 54 | 1 | 2 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001164014.1 | 6 | MANE Select | |
| Ensembl | ENSP00000438465.1 | 6 | MANE Select | |
| RefSeq | NP_001164015.1 | 6 | Standard | |
| RefSeq | NP_612642.2 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TNF signaling pathway - Homo sapiens (human)
- Mitophagy - animal - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Receptor Mediated Mitophagy
- Mitophagy
Biological Process
- protein dephosphorylation
- macroautophagy
- positive regulation of GTPase activity
- necroptotic process
- negative regulation of cold-induced thermogenesis
Molecular Function
- protein serine/threonine phosphatase activity
- GTPase activator activity
- protein binding
- phosphatase activity
- protein-containing complex binding
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000498926
- Coding exons
- 6
- Length
- 11824
- Individuals with no LoFs
- 125466
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125489
- p
- 0.0000916
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.964 | 128 | 163 | 0.787 | 0.0000117 | 1836 |
| Missense (PolyPhen) | 33 | 55.608 | 0.59344 | 570 | ||
| Synonymous | -1.31 | 85 | 70.9 | 1.20 | 0.00000541 | 616 |
| Loss of Function | 1.03 | 8 | 11.8 | 0.676 | 7.69e-7 | 134 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2- dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore. {ECO:0000269|PubMed:18387606, ECO:0000269|PubMed:19590015, ECO:0000269|PubMed:22265414}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.274
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.788
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |