Progressive cardiac conduction disease

Gene: POPDC2

Green List (high evidence)

Comment on list classification: There are five unrelated families reported with cardiac conduction disease and with biallelic POPDC2 variants. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 22 Apr 2026, 5:26 p.m. | Last Modified: 22 Apr 2026, 5:27 p.m.

Panel Version: 2.15

PMID:40409267 (2025) reported the identification of biallelic variants in POPDC2 gene in six patients from four families presenting with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects, and hypertrophic cardiomyopathy. Modelling and electrophysiological studies suggested effects of identified POPDC2 variants on cAMP binding and TREK-1 current.

PMID:41456958 (2026) reported the identification of a novel homozygous POPDC2 variant in a patient presenting with early-onset cardiac conduction disease and hypertrophic cardiomyopathy.

This gene has been associated with relevant phenotype in OMIM (MIM #621367, record last accessed on 22 April 2026), but not yet in Gene2Phenotype or ClinGen.
Sources: Literature

Created: 22 Apr 2026, 5:25 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367; cardiac conduction disease with or without cardiomyopathy 2, MONDO:0700389

Publications

• 40409267
• 41456958