PDE1C

phosphodiesterase 1C, the group of Phosphodiesterases

Basic information

Region (hg38): 7:31751178-32428131

Links

ENSG00000154678 ∙ NCBI:5137 ∙ OMIM:602987 ∙ HGNC:8776 ∙ Uniprot:Q14123 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal dominant 74 (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal dominant 74 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 74	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	29860631

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE1C gene.

• not provided (45 variants)
• Inborn genetic diseases (12 variants)
• Hearing loss, autosomal dominant 74 (5 variants)
• PDE1C-related condition (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE1C 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	6	10
missense			18	3	2	23
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					28	28
Total	0	0	19	7	36

Variants in PDE1C

This is a list of pathogenic ClinVar variants found in the PDE1C region.

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

Position	Type	Phenotype	Significance	ClinVar
7-31753443-C-T		PDE1C-related disorder	Likely benign (May 03, 2023)
7-31753513-G-A		PDE1C-related disorder	Likely benign (Aug 19, 2020)
7-31753535-C-T			Benign (Jul 01, 2022)
7-31753676-T-G			Benign (May 25, 2021)
7-31775671-C-G			Benign (Dec 31, 2019)
7-31775683-C-T			Likely benign (Aug 01, 2023)
7-31775712-C-T		PDE1C-related disorder	Benign (Sep 04, 2019)
7-31775720-C-T		PDE1C-related disorder	Benign/Likely benign (Jul 14, 2020)
7-31790481-A-G			Benign (May 13, 2021)
7-31809034-C-A		not specified	Uncertain significance (Dec 14, 2023)
7-31809036-G-A		not specified	Uncertain significance (Jan 26, 2022)
7-31809056-G-A			Likely benign (Apr 05, 2018)
7-31809067-G-A		not specified	Uncertain significance (Aug 12, 2021)
7-31809079-C-T		not specified	Uncertain significance (Apr 07, 2023)
7-31809087-T-C		PDE1C-related disorder	Uncertain significance (Feb 20, 2023)
7-31809092-A-G		Hearing loss, autosomal dominant 74	Benign (Sep 05, 2021)
7-31809149-T-C			Benign (May 14, 2021)
7-31815781-A-G			Benign (May 22, 2021)
7-31815806-A-G			Benign (May 13, 2021)
7-31815955-G-A		Hearing loss, autosomal dominant 74	Benign (Sep 05, 2021)
7-31815963-A-C		PDE1C-related disorder	Benign/Likely benign (Feb 01, 2023)
7-31815964-G-A		Hearing loss, autosomal dominant 74	Benign (Sep 05, 2021)
7-31815978-G-T		PDE1C-related disorder	Uncertain significance (Mar 23, 2023)
7-31815998-C-T		not specified	Uncertain significance (Nov 08, 2022)
7-31815999-G-A		not specified	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE1C	protein_coding	protein_coding	ENST00000396193	19	548149

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.39e-9	1.00	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	355	437	0.813	0.0000247	5035
Missense in Polyphen		112	173.94	0.64389		2037
Synonymous	0.282	155	160	0.972	0.00000913	1423
Loss of Function	3.13	21	43.2	0.486	0.00000229	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000355
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000163
Finnish	0.0000939	0.0000924
European (Non-Finnish)	0.000165	0.000158
Middle Eastern	0.000167	0.000163
South Asian	0.000230	0.000229
Other	0.000335	0.000326

dbNSFP

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 high affinity for both cAMP and cGMP.
• Pathway: 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);Morphine addiction - Homo sapiens (human);G Protein Signaling Pathways;Phosphodiesterases in neuronal function;Signaling by GPCR;Signal Transduction;Calmodulin induced events;CaM pathway;Cam-PDE 1 activation;Purine nucleotides nucleosides metabolism;DAG and IP3 signaling;Ca-dependent events;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.750
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.52

Haploinsufficiency Scores

• pHI: 0.243
• hipred: Y
• hipred_score: 0.553
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.617

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde1c
• Phenotype: taste/olfaction phenotype

Gene ontology

• Biological process: signal transduction
• Cellular component: cytosol;neuronal cell body
• Molecular function: calmodulin-dependent cyclic-nucleotide phosphodiesterase activity;calmodulin binding;metal ion binding;calcium- and calmodulin-regulated 3',5'-cyclic-GMP phosphodiesterase activity