PTGIS

protein-coding

prostaglandin I2 synthase, the group of Cytochrome P450 family 8

Gene summary

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000961.4

Inheritance

—

ClinVar variants

P:2U:97B:8

Top phenotype

PTGIS-related disorder

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr20:49,503,874-49,568,137

External References & Databases

Ensembl (ENSG00000124212)

Transcript & Mutation Effects

hg38 • Region Span ~64.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

essential hypertension, geneticLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007781

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTGIS variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 4

PTGIS-related disorderTotal: 2

Essential hypertensionTotal: 2

Essential hypertension, geneticTotal: 1

Childhood-onset schizophreniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000961.4. 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 clinvar	1 clinvar	2 clinvar	4
missense		1 clinvar	93 clinvar	4 clinvar	1 clinvar	99
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	1	1	97	5	3	107

Highest pathogenic variant AF is 0.001178278

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000961.4	RefSeq	NP_000952.1	10	MANE Select
ENST00000244043.5	Ensembl	ENSP00000244043.3	10	MANE Select
ENST00000918261.1	Ensembl	ENSP00000588320.1	8	Standard
ENST00000918261.2	Ensembl	ENSP00000588320.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arachidonic acid metabolism - Homo sapiens (human)
Phenytoin Pathway, Pharmacokinetics
Celecoxib Pathway, Pharmacodynamics
Etodolac Action Pathway
Ketoprofen Action Pathway

Biological Process

prostaglandin biosynthetic process
icosanoid metabolic process
embryo implantation
cyclooxygenase pathway
negative regulation of NF-kappaB transcription factor activity

Molecular Function

monooxygenase activity
iron ion binding
protein binding
prostaglandin-I synthase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen

Cellular Component

extracellular space
nucleus
endoplasmic reticulum
endoplasmic reticulum membrane
caveola

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000244043
Coding exons: 10
Length: 64273
Individuals with no LoFs: 125624
Homozygous LoFs: 0
Heterozygous LoFs: 124
Defined: 125748
p: 0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.369	310	292	1.06	0.0000192	3248
Missense (PolyPhen)		100	101.94	0.98101		1169
Synonymous	-0.333	127	122	1.04	0.00000833	1020
Loss of Function	1.19	17	23.2	0.733	0.00000137	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00098	0.00098	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00045	0.00041	rare
South Asian	0.00049	0.00049	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2). {ECO:0000269|PubMed:18032380, ECO:0000269|PubMed:25623425}.;

Recessive Scores

pRec: 0.277

Intolerance Scores

LoFtool: 0.936
RVIS EVS: -0.35
RVIS percentile EVS: 29.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.929

Gene Damage Prediction

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