PPARGC1B
protein-codingPPARG coactivator 1 beta, the group of RNA binding motif containing|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene stimulates the activity of several transcription factors and nuclear receptors, including estrogen receptor alpha, nuclear respiratory factor 1, and glucocorticoid receptor. The encoded protein may be involved in fat oxidation, non-oxidative glucose metabolism, and the regulation of energy expenditure. This protein is downregulated in prediabetic and type 2 diabetes mellitus patients. Certain allelic variations in this gene increase the risk of the development of obesity. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~124.7 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 PPARGC1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133263.4. 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 | 1 | 1 | 3 | 5 | ||
| missense | 184 | 9 | 8 | 201 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 189 | 10 | 11 | 210 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_573570.3 | 12 | MANE Select | |
| Ensembl | ENSP00000312649.5 | 12 | MANE Select | |
| RefSeq | NP_001166169.1 | 11 | Standard | |
| RefSeq | NP_001166170.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin resistance - Homo sapiens (human)
- AMP-activated Protein Kinase (AMPK) Signaling
- Energy Metabolism
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
- Differentiation of white and brown adipocyte
Biological Process
- ossification
- regulation of transcription, DNA-templated
- mitochondrial transcription
- actin filament organization
- positive regulation of alkaline phosphatase activity
Molecular Function
- transcription coregulator activity
- RNA binding
- transcription factor binding
- estrogen receptor binding
- nuclear receptor transcription coactivator activity
Cellular Component
- nucleus
- nucleoplasm
- mitochondrion
- mediator complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000309241
- Coding exons
- 12
- Length
- 124725
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.503 | 566 | 601 | 0.942 | 0.0000362 | 6582 |
| Missense (PolyPhen) | 143 | 164.58 | 0.86888 | 1848 | ||
| Synonymous | -0.985 | 274 | 254 | 1.08 | 0.0000158 | 2080 |
| Loss of Function | 4.89 | 10 | 45.7 | 0.219 | 0.00000254 | 499 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000098 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non-oxidative glucose metabolism and in the regulation of energy expenditure. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. {ECO:0000269|PubMed:11854298, ECO:0000269|PubMed:12678921, ECO:0000269|PubMed:15546003, ECO:0000269|PubMed:23836911}.;
Recessive Scores
- pRec
- 0.214
Intolerance Scores
- LoFtool
- 0.489
- RVIS EVS
- 1.06
- RVIS percentile EVS
- 91.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.846
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |