PDE9A

phosphodiesterase 9A, the group of Phosphodiesterases

Basic information

Region (hg38): 21:42653620-42775509

Links

ENSG00000160191 ∙ NCBI:5152 ∙ OMIM:602973 ∙ HGNC:8795 ∙ Uniprot:O76083 ∙ 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 PDE9A gene.

• Inborn genetic diseases (33 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE9A 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						0
missense			29	4	1	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	29	4	1

Variants in PDE9A

This is a list of pathogenic ClinVar variants found in the PDE9A region.

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

Position	Type	Phenotype	Significance	ClinVar
21-42653873-G-A		not specified	Uncertain significance (May 03, 2023)
21-42686205-A-C		not specified	Uncertain significance (Jan 02, 2024)
21-42687923-G-A		not specified	Likely benign (Oct 10, 2023)
21-42687944-C-T		not specified	Likely benign (Jan 09, 2024)
21-42687945-G-A		not specified	Uncertain significance (Aug 30, 2021)
21-42687948-G-A		not specified	Uncertain significance (Jun 02, 2023)
21-42687951-G-A		not specified	Uncertain significance (Sep 15, 2021)
21-42687966-G-A		not specified	Uncertain significance (Aug 17, 2021)
21-42698974-G-A		not specified	Likely benign (Jun 13, 2023)
21-42698987-C-G		not specified	Uncertain significance (Oct 17, 2023)
21-42731800-G-A		not specified	Uncertain significance (Jan 06, 2023)
21-42731818-G-C		not specified	Uncertain significance (Jan 19, 2024)
21-42731859-C-T		not specified	Uncertain significance (Jun 07, 2022)
21-42732093-G-A		not specified	Uncertain significance (Jul 13, 2022)
21-42732105-G-A		not specified	Uncertain significance (Apr 28, 2023)
21-42733369-A-G		not specified	Uncertain significance (Oct 13, 2023)
21-42733418-G-A		not specified	Uncertain significance (Jan 26, 2022)
21-42743784-C-A		not specified	Uncertain significance (Aug 04, 2023)
21-42743785-T-C		not specified	Uncertain significance (Nov 10, 2022)
21-42743818-A-G		not specified	Uncertain significance (Jan 23, 2024)
21-42751177-G-A		not specified	Uncertain significance (Oct 03, 2022)
21-42751186-A-G		not specified	Uncertain significance (Aug 10, 2021)
21-42754033-C-T		not specified	Uncertain significance (Sep 07, 2022)
21-42754041-G-A		not specified	Uncertain significance (Dec 16, 2023)
21-42759029-G-C		not specified	Uncertain significance (Jan 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE9A	protein_coding	protein_coding	ENST00000291539	20	121874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00456	0.995	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	307	365	0.840	0.0000221	3945
Missense in Polyphen		81	114.1	0.70988		1230
Synonymous	0.482	133	140	0.948	0.00000962	1044
Loss of Function	4.11	12	40.1	0.300	0.00000213	440

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000384	0.000381
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.000384	0.000381
South Asian	0.000131	0.000131
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP (PubMed:9624146, PubMed:18757755, PubMed:21483814). Specifically regulates natriuretic-peptide- dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (By similarity). {ECO:0000250|UniProtKB:Q8QZV1, ECO:0000269|PubMed:18757755, ECO:0000269|PubMed:21483814, ECO:0000269|PubMed:25799991, ECO:0000269|PubMed:9624146, ECO:0000305}.
• Pathway: Purine metabolism - Homo sapiens (human);Phosphodiesterases in neuronal function;Purine nucleotides nucleosides metabolism;Hemostasis;cGMP effects;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;Regulation of Androgen receptor activity (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.262
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.63

Haploinsufficiency Scores

• pHI: 0.455
• hipred: Y
• hipred_score: 0.585
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde9a
• Phenotype: homeostasis/metabolism 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: signal transduction;positive regulation of cardiac muscle hypertrophy;cGMP-mediated signaling;cGMP metabolic process;cGMP catabolic process
• Cellular component: endoplasmic reticulum;Golgi apparatus;cytosol;ruffle membrane;sarcolemma;perikaryon;perinuclear region of cytoplasm
• Molecular function: 3',5'-cyclic-nucleotide phosphodiesterase activity;protein binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity