PPARGC1A

PPARG coactivator 1 alpha, the group of RNA binding motif containing

Basic information

Region (hg38): 4:23755040-23904089

Previous symbols: [ "PPARGC1" ]

Links

ENSG00000109819 ∙ NCBI:10891 ∙ OMIM:604517 ∙ HGNC:9237 ∙ Uniprot:Q9UBK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPARGC1A gene.

• Inborn genetic diseases (16 variants)
• not provided (15 variants)
• PPARGC1A-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPARGC1A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			18	1	3	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	18	6	6

Variants in PPARGC1A

This is a list of pathogenic ClinVar variants found in the PPARGC1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-23795844-G-T			Uncertain significance (Nov 11, 2019)
4-23801855-C-T		not specified	Uncertain significance (Nov 06, 2023)
4-23801889-G-A			Benign (May 21, 2018)
4-23802234-G-A		not specified	Uncertain significance (Jul 15, 2021)
4-23802243-C-T		not specified	Uncertain significance (Sep 22, 2021)
4-23812781-G-A		not specified	Uncertain significance (Aug 02, 2023)
4-23813084-G-A		PPARGC1A-related disorder	Benign (Feb 22, 2019)
4-23813087-C-T		PPARGC1A-related disorder	Benign/Likely benign (Oct 01, 2022)
4-23813090-T-G		not specified	Uncertain significance (Feb 13, 2024)
4-23813756-C-T		not specified	Uncertain significance (Feb 23, 2023)
4-23813787-G-A			Benign (Jul 05, 2018)
4-23813883-A-G		not specified	Uncertain significance (Oct 13, 2023)
4-23813899-C-T		PPARGC1A-related disorder	Benign (Oct 18, 2019)
4-23813997-T-G		PPARGC1A-related disorder	Uncertain significance (Oct 24, 2022)
4-23814039-C-T		PPARGC1A-related disorder	Benign (Oct 17, 2019)
4-23814051-C-T		not specified	Uncertain significance (May 15, 2023)
4-23814055-G-A		PPARGC1A-related disorder	Benign (Mar 14, 2019)
4-23814058-G-A		PPARGC1A-related disorder	Benign (Dec 03, 2019)
4-23814102-C-T		not specified	Uncertain significance (Dec 15, 2023)
4-23814107-C-T		not specified	Uncertain significance (Dec 14, 2022)
4-23814138-T-C		not specified	Uncertain significance (Mar 07, 2024)
4-23814170-A-G		PPARGC1A-related disorder	Benign (Jul 29, 2019)
4-23814220-C-T			Likely benign (May 30, 2018)
4-23814242-T-C		not specified	Uncertain significance (Apr 26, 2023)
4-23814255-G-T		PPARGC1A-related disorder	Benign (May 24, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPARGC1A	protein_coding	protein_coding	ENST00000264867	13	149049

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00270	125720	0	11	125731	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.00	385	444	0.866	0.0000247	5226
Missense in Polyphen		97	126.79	0.76502		1584
Synonymous	-0.186	169	166	1.02	0.00000935	1511
Loss of Function	5.08	5	39.4	0.127	0.00000200	481

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000718	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also involved in the integration of the circadian rhythms and energy metabolism. Required for oscillatory expression of clock genes, such as ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK. {ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:20005308, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:23836911}.
• Pathway: Adipocytokine signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;Energy Metabolism;SREBF and miR33 in cholesterol and lipid homeostasis;Adipogenesis;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Farnesoid X Receptor Pathway;Nuclear Receptors Meta-Pathway;Lipid storage and perilipins in skeletal muscle;Differentiation of white and brown adipocyte;FTO Obesity Variant Mechanism;Transcription factor regulation in adipogenesis;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Mitochondrial Gene Expression;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Liver steatosis AOP;Caloric restriction and aging;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Prostaglandin Synthesis and Regulation;Developmental Biology;Transcriptional regulation by RUNX2;Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;Circadian Clock;regulation of pgc-1a;Generic Transcription Pathway;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation;ATF-2 transcription factor network;Activation of PPARGC1A (PGC-1alpha) by phosphorylation;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;mTOR signaling pathway;Signaling mediated by p38-alpha and p38-beta;Signaling events mediated by HDAC Class III;Regulation of RUNX2 expression and activity;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.840

Intolerance Scores

• loftool: 0.0500
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.57

Haploinsufficiency Scores

• pHI: 0.986
• hipred: Y
• hipred_score: 0.825
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ppargc1a
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm

Zebrafish Information Network

• Gene name: ppargc1a
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: response to reactive oxygen species;autophagy of mitochondrion;temperature homeostasis;cellular glucose homeostasis;negative regulation of protein phosphorylation;response to dietary excess;response to ischemia;galactose metabolic process;gluconeogenesis;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;mRNA processing;mitochondrion organization;aging;digestion;circadian rhythm;androgen metabolic process;RNA splicing;response to cold;positive regulation of gene expression;positive regulation of mitochondrion organization;skeletal muscle atrophy;response to muscle activity;response to electrical stimulus involved in regulation of muscle adaptation;negative regulation of smooth muscle cell migration;fatty acid oxidation;cerebellum development;respiratory electron transport chain;androgen receptor signaling pathway;forebrain development;circadian regulation of gene expression;cellular response to oxidative stress;positive regulation of histone acetylation;cellular response to potassium ion;response to starvation;regulation of circadian rhythm;response to leucine;negative regulation of neuron apoptotic process;cellular respiration;positive regulation of gluconeogenesis;negative regulation of glycolytic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of fatty acid oxidation;positive regulation of smooth muscle cell proliferation;negative regulation of smooth muscle cell proliferation;protein stabilization;brown fat cell differentiation;positive regulation of DNA-binding transcription factor activity;flavone metabolic process;adipose tissue development;protein-containing complex assembly;cellular response to lipopolysaccharide;cellular response to nitrite;cellular response to caffeine;cellular response to fructose stimulus;cellular response to glucose stimulus;cellular response to interleukin-6;cellular response to tumor necrosis factor;cellular response to follicle-stimulating hormone stimulus;cellular response to estradiol stimulus;cellular response to hypoxia;cellular response to transforming growth factor beta stimulus;response to epinephrine;response to norepinephrine;negative regulation of mitochondrial fission;energy homeostasis;cellular response to thyroid hormone stimulus;positive regulation of cold-induced thermogenesis;negative regulation of neuron death;response to metformin;positive regulation of cellular respiration;positive regulation of mitochondrial DNA metabolic process;positive regulation of muscle tissue development;positive regulation of glomerular visceral epithelial cell apoptotic process;cellular response to ionomycin;cellular response to resveratrol;response to methionine;adaptive thermogenesis;positive regulation of progesterone biosynthetic process;negative regulation of signaling receptor activity;regulation of NMDA receptor activity;positive regulation of ATP biosynthetic process
• Cellular component: nucleus;nucleoplasm;nuclear euchromatin;PML body;cytosolic ribosome;neuronal cell body;intracellular membrane-bounded organelle;apical dendrite;subsarcolemmal mitochondrion;interfibrillar mitochondrion
• Molecular function: DNA binding;transcription coregulator activity;transcription coactivator activity;RNA binding;protein binding;transcription factor binding;nuclear receptor binding;estrogen receptor binding;nuclear receptor transcription coactivator activity;chromatin DNA binding;ubiquitin protein ligase binding;peroxisome proliferator activated receptor binding;alpha-tubulin binding;sequence-specific DNA binding;androgen receptor binding;promoter-specific chromatin binding