PTGES3

protein-coding

prostaglandin E synthase 3

Gene summary

This gene encodes an enzyme that converts prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). This protein functions as a co-chaperone with heat shock protein 90 (HSP90), localizing to response elements in DNA and disrupting transcriptional activation complexes. Alternative splicing results in multiple transcript variants. There are multiple pseudogenes of this gene on several different chromosomes. [provided by RefSeq, Feb 2016]

MANE transcript

NM_006601.7

Inheritance

—

ClinVar variants

U:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr12:56,663,341-56,688,408

External References & Databases

Ensembl (ENSG00000110958)

Transcript & Mutation Effects

hg38 • Region Span ~25.1 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 PTGES3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006601.7. 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						0
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	12	0	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006601.7	RefSeq	NP_006592.3	8	MANE Select
ENST00000262033.11	Ensembl	ENSP00000262033.6	8	MANE Select
NM_001282601.2	RefSeq	NP_001269530.1	7	Standard
NM_001282602.2	RefSeq	NP_001269531.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arachidonic acid metabolism - Homo sapiens (human)
Aryl Hydrocarbon Receptor Pathway
Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway
Signal Transduction

Biological Process

telomere maintenance
prostaglandin biosynthetic process
protein folding
xenobiotic metabolic process
telomere maintenance via telomerase

Molecular Function

telomerase activity
protein binding
prostaglandin-E synthase activity
unfolded protein binding
chaperone binding

Cellular Component

chromosome, telomeric region
nucleus
nucleoplasm
telomerase holoenzyme complex
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262033
Coding exons: 8
Length: 25033
Individuals with no LoFs: 119200
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 119202
p: 0.00000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	49	81.2	0.604	0.00000394	1099
Missense (PolyPhen)		7	19.152	0.3655		300
Synonymous	0.194	25	26.3	0.952	0.00000144	241
Loss of Function	3.32	0	12.8	0.00	7.01e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000034	0.000033	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000096	0.0000090	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, ECO:0000269|PubMed:24711448}.;

Recessive Scores

pRec: 0.281

Intolerance Scores

LoFtool: 0.400
RVIS EVS: 0.19
RVIS percentile EVS: 66.57

Essentials

Essential (CRISPR): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.694

Gene Damage Prediction

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