PDE1C

Chr 7

phosphodiesterase 1C

Also known as: DFNA74, Hcam3, cam-PDE 1C, hCam-3

NCBI Gene: 5137ENSG00000154678UniProt: Q14123

This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal dominant, 74
314
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PDE1C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 198 VUS of 314 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.000
Z-score 3.13
OE 0.49 (0.34–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.39Z-score
OE missense 0.81 (0.74–0.89)
355 obs / 436.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.34–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.74–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 21 / 43.2Missense obs/exp: 355 / 436.6Syn Z: 0.28

ClinVar Variant Classifications

314 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic8
VUS198
Likely Benign32
Benign57
19
Pathogenic
8
Likely Pathogenic
198
VUS
32
Likely Benign
57
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
1
1
6
0
8
VUS
2
188
8
0
198
Likely Benign
0
20
3
9
32
Benign
1
5
40
11
57
Total42147620314

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PDE1C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare and novel variant load threshold for KIF7, GJA1 and PDE1C genes elevates the risk of severity of congenital heart defects in Down syndrome.
Ganguly A et al.·PLoS One
2025
A dominant variant in the PDE1C gene is associated with nonsyndromic hearing loss.
Wang L et al.·Hum Genet
2018
Myocardial Phosphodiesterases and Their Role in cGMP Regulation.
Dunkerly-Eyring B et al.·J Cardiovasc Pharmacol
2020Review
Phosphodiesterase expression in the normal and failing heart.
Li EA et al.·Arch Biochem Biophys
2019
Turning on cGMP-dependent pathways to treat cardiac dysfunctions: boom, bust, and beyond.
Lukowski R et al.·Trends Pharmacol Sci
2014Review
Cyclic nucleotide phosphodiesterase 1 and vascular aging.
Yan C·Clin Sci (Lond)
2015
Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.
Rybalkin SD et al.·J Clin Invest
1997
Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population.
Tomofuji Y et al.·Cell Rep
2023
Myopia in African Americans Is Significantly Linked to Chromosome 7p15.2-14.2.
Simpson CL et al.·Invest Ophthalmol Vis Sci
2021
Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.
Schuit E et al.·Cochrane Database Syst Rev
2017Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools