PDE1A

protein-coding

phosphodiesterase 1A, the group of Phosphodiesterases

Gene summary

Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).[supplied by OMIM, Oct 2009]

MANE transcript

NM_001363871.4

Inheritance

—

ClinVar variants

U:57B:4

Top phenotype

PDE1A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:182,139,968-182,523,359

External References & Databases

Ensembl (ENSG00000115252)

Transcript & Mutation Effects

hg38 • Region Span ~383.4 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 PDE1A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 7

PDE1A-related disorderTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001363871.4. 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				2 clinvar		2
missense			56 clinvar	2 clinvar		58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	57	4	0	61

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001363871.4	RefSeq	NP_001350800.1	14	MANE Select
ENST00000409365.6	Ensembl	ENSP00000386767.1	14	MANE Select
NM_001003683.3	RefSeq	NP_001003683.1	14	Standard
NM_001258312.3	RefSeq	NP_001245241.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pde1a	Danio rerio	Structure: pronephric tubule Quality: dilated abnormal

Gene / Model

Organism

Observed Phenotype

pde1a

Danio rerio

Structure: pronephric tubule

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Calcium signaling pathway - Homo sapiens (human)
Renin secretion - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Taste transduction - Homo sapiens (human)
Olfactory transduction - Homo sapiens (human)

Biological Process

G protein-coupled receptor signaling pathway
regulation of smooth muscle cell apoptotic process
cGMP catabolic process
regulation of smooth muscle cell proliferation

Molecular Function

3',5'-cyclic-AMP phosphodiesterase activity
calmodulin-dependent cyclic-nucleotide phosphodiesterase activity
calmodulin binding
metal ion binding
3',5'-cyclic-GMP phosphodiesterase activity

Cellular Component

nucleus
cytosol
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000435564
Coding exons: 14
Length: 383157
Individuals with no LoFs: 125725
Homozygous LoFs: 1
Heterozygous LoFs: 17
Defined: 125743
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.967	246	293	0.841	0.0000150	3587
Missense (PolyPhen)		91	130.4	0.69785		1619
Synonymous	-0.375	106	101	1.05	0.00000521	996
Loss of Function	3.53	9	29.8	0.302	0.00000148	376

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.00020	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cyclic nucleotide phosphodiesterase with a dual- specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cGMP than for cAMP.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.376
RVIS EVS: -0.73
RVIS percentile EVS: 14.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.561

Gene Damage Prediction

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