PTGIS

prostaglandin I2 synthase, the group of Cytochrome P450 family 8

Basic information

Region (hg38): 20:49503874-49568137

Links

ENSG00000124212 ∙ NCBI:5740 ∙ OMIM:601699 ∙ HGNC:9603 ∙ Uniprot:Q16647 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• essential hypertension, genetic (Limited), mode of inheritance: Unknown

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTGIS 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					4	4
missense		1	44	3	1	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	44	3	6

Variants in PTGIS

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

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

Position	Type	Phenotype	Significance	ClinVar
20-49507928-G-A		not specified	Uncertain significance (Apr 06, 2024)
20-49507934-G-A		not specified	Uncertain significance (Mar 24, 2023)
20-49507950-G-T		not specified	Uncertain significance (Oct 30, 2023)
20-49508018-C-T		not specified	Uncertain significance (Feb 08, 2023)
20-49508020-T-A		not specified	Uncertain significance (Apr 12, 2024)
20-49508038-A-C		not specified	Uncertain significance (Jan 23, 2023)
20-49508041-T-G		not specified	Uncertain significance (Jan 26, 2023)
20-49508045-C-T			Likely benign (Mar 29, 2018)
20-49508057-A-G		not specified	Uncertain significance (Feb 22, 2023)
20-49511026-A-G		Essential hypertension	Pathogenic (Oct 11, 2002)
20-49513169-G-T		PTGIS-related disorder	Benign (Oct 21, 2019)
20-49513172-C-T		not specified	Uncertain significance (Nov 28, 2023)
20-49513183-G-A		not specified	Uncertain significance (Feb 28, 2024)
20-49513213-G-T		not specified	Uncertain significance (Dec 19, 2022)
20-49513256-C-G		not specified	Uncertain significance (Apr 04, 2023)
20-49513256-C-T		not specified	Uncertain significance (Oct 12, 2022)
20-49514323-G-A		not specified	Uncertain significance (Jul 05, 2023)
20-49514337-G-A		not specified	Uncertain significance (Dec 05, 2022)
20-49514389-T-C		not specified	Uncertain significance (Oct 05, 2022)
20-49514391-T-C		not specified	Uncertain significance (Jul 19, 2023)
20-49524089-C-T		Childhood-onset schizophrenia	Likely pathogenic (Jan 01, 2014)
20-49524090-G-A		not specified	Uncertain significance (Jun 21, 2021)
20-49524141-T-A		not specified	Uncertain significance (Jan 27, 2022)
20-49524145-C-T		PTGIS-related disorder	Benign (Oct 21, 2019)
20-49524148-C-A		not specified	Uncertain significance (Jul 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTGIS	protein_coding	protein_coding	ENST00000244043	10	64273

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.20e-9	0.547	125624	0	124	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.369	310	292	1.06	0.0000192	3248
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000868	0.000868
Ashkenazi Jewish	0.00198	0.00199
East Asian	0.000979	0.000979
Finnish	0.00	0.00
European (Non-Finnish)	0.000450	0.000413
Middle Eastern	0.000979	0.000979
South Asian	0.000490	0.000490
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2). {ECO:0000269|PubMed:18032380, ECO:0000269|PubMed:25623425}.
• Pathway: Arachidonic acid metabolism - Homo sapiens (human);Phenytoin Pathway, Pharmacokinetics;Celecoxib Pathway, Pharmacodynamics;Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Eicosanoid Synthesis;Adipogenesis;Prostaglandin Synthesis and Regulation;Phase I - Functionalization of compounds;eicosanoid metabolism;Metabolism of lipids;Synthesis of Prostaglandins (PG) and Thromboxanes (TX);Prostaglandin Leukotriene metabolism;Arachidonic acid metabolism;Sterols are 12-hydroxylated by CYP8B1;Endogenous sterols;Eicosanoids;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Fatty acid metabolism;Nicotinamide salvaging;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of steroids;Metabolism of vitamins and cofactors;C20 prostanoid biosynthesis;Prostaglandin formation from arachidonate (Consensus)

Recessive Scores

• pRec: 0.277

Intolerance Scores

• loftool: 0.936
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.49

Haploinsufficiency Scores

• pHI: 0.365
• hipred: N
• hipred_score: 0.307
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptgis
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype; 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)

Gene ontology

• Biological process: prostaglandin biosynthetic process;icosanoid metabolic process;embryo implantation;cyclooxygenase pathway;negative regulation of NF-kappaB transcription factor activity;NAD biosynthesis via nicotinamide riboside salvage pathway;positive regulation of peroxisome proliferator activated receptor signaling pathway;negative regulation of nitric oxide biosynthetic process;positive regulation of angiogenesis;decidualization;negative regulation of inflammatory response;oxidation-reduction process;cellular response to interleukin-1;cellular response to interleukin-6;cellular response to hypoxia;apoptotic signaling pathway;positive regulation of execution phase of apoptosis
• Cellular component: extracellular space;nucleus;endoplasmic reticulum;endoplasmic reticulum membrane;caveola;integral component of membrane
• 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;heme binding