PPARGC1A

Chr 4

PPARG coactivator 1 alpha

Also known as: LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A, PPARGC1

The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
4
Active trials
240
Pubs (1 yr)
P/LP submissions
P/LP missense
0.27
LOEUF· LoF intol.
LOF
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.27LOEUF
pLI 0.997
Z-score 5.08
OE 0.13 (0.070.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.00Z-score
OE missense 0.87 (0.800.94)
385 obs / 444.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.13 (0.070.27)
00.351.4
Missense OE?0.87 (0.800.94)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 5 / 39.4Missense obs/exp: 385 / 444.4Syn Z: -0.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPARGC1A · protein map & ClinVar variants

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