PPRC1

protein-coding

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

Gene summary

The protein encoded by this gene is similar to PPAR-gamma coactivator 1 (PPARGC1/PGC-1), a protein that can activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF1). This protein has been shown to interact with NRF1. It is thought to be a functional relative of PPAR-gamma coactivator 1 that activates mitochondrial biogenesis through NRF1 in response to proliferative signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

MANE transcript

NM_015062.5

Inheritance

—

ClinVar variants

U:286B:40

Top phenotype

PPRC1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr10:102,132,994-102,150,333

External References & Databases

Ensembl (ENSG00000148840)

Transcript & Mutation Effects

hg38 • Region Span ~17.3 kb

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GenCC 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 PPRC1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 278

PPRC1-related disorderTotal: 26

not providedTotal: 15

PPRC1-related conditonTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015062.5. 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			3 clinvar	14 clinvar		17
missense			273 clinvar	20 clinvar	6 clinvar	299
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	286	34	6	326

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015062.5	RefSeq	NP_055877.3	14	MANE Select
ENST00000278070.7	Ensembl	ENSP00000278070.2	14	MANE Select
NM_001288727.2	RefSeq	NP_001275656.1	12	Standard
NM_001288728.2	RefSeq	NP_001275657.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Energy Metabolism
Mitochondrial Gene Expression
Transcriptional activation of mitochondrial biogenesis
Mitochondrial biogenesis
Organelle biogenesis and maintenance

Biological Process

mitochondrion organization
positive regulation of transcription by RNA polymerase II
positive regulation of DNA-binding transcription factor activity

Molecular Function

transcription coregulator activity
RNA binding
transcription factor binding
nuclear receptor transcription coactivator activity

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278070
Coding exons: 14
Length: 17296
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.244	898	919	0.977	0.0000519	10539
Missense (PolyPhen)		214	263.67	0.81162		3194
Synonymous	-0.745	382	364	1.05	0.0000193	3755
Loss of Function	6.72	4	60.4	0.0662	0.00000374	675

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a coactivator during transcriptional activation of nuclear genes related to mitochondrial biogenesis and cell growth. Involved in the transcription coactivation of CREB and NRF1 target genes. {ECO:0000269|PubMed:11340167, ECO:0000269|PubMed:16908542}.;

Recessive Scores

pRec: 0.685

Intolerance Scores

LoFtool: 0.239
RVIS EVS: 0.44
RVIS percentile EVS: 77.46

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.960

Gene Damage Prediction

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