POPDC1

Chr 6AR

popeye domain cAMP effector 1

NCBI Gene: 11149ENSG00000112276UniProt: Q8NE79

Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. Involved in the formation and regulation of the tight junction (TJ) paracellular permeability barrier in epithelial cells (PubMed:16188940). Plays a role in VAMP3-mediated vesicular transport and recycling of different receptor molecules through its interaction with VAMP3. Plays a role in the regulation of cell shape and movement by modulating the Rho-family GTPase activity through its interaction with ARHGEF25/GEFT. Induces primordial adhesive contact and aggregation of epithelial cells in a Ca(2+)-independent manner. Also involved in striated muscle regeneration and repair and in the regulation of cell spreading (By similarity). Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density (PubMed:26642364). Is also a caveolae-associated protein important for the preservation of caveolae structural and functional integrity as well as for heart protection against ischemia injury

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal recessive 25MIM #616812
AR
110
ClinVar variants
23
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— POPDC1
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 52 VUS of 110 total submissions
Some data sources returned errors (1)

gnomad: Error: Gene not found

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic6
VUS52
Likely Benign16
Benign18
Conflicting1
17
Pathogenic
6
Likely Pathogenic
52
VUS
16
Likely Benign
18
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
2
1
3
0
6
VUS
1
45
5
1
52
Likely Benign
0
2
8
6
16
Benign
0
3
15
0
18
Conflicting
—1
Total351487110

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

View in ClinVar →

Protein Context — Lollipop Plot

POPDC1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy, limb-girdle, autosomal recessive 25

MIM #616812

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The expanding phenotypes of cohesinopathies: one ring to rule them all!
Piché J et al.·Cell Cycle
2019Review
POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.
Stoyek MR et al.·Genes (Basel)
2024Functional
Proteomic and morphological insights and clinical presentation of two young patients with novel mutations of BVES (POPDC1).
Gangfuß A et al.·Mol Genet Metab
2022Case report
A novel biallelic variant in the Popeye domain-containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25.
Mahmood A et al.·Clin Genet
2023Case report
POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking.
Schindler RF et al.·J Clin Invest
2016
Dysregulation of POPDC1 promotes breast cancer cell migration and proliferation.
Amunjela JN et al.·Biosci Rep
2017
The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis.
Amunjela JN et al.·Cells
2019Review
POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines.
Amunjela JN et al.·Cancer Lett
2017
Homozygous missense variant in POPDC3 causes recessive limb-girdle muscular dystrophy type 26.
Ullah A et al.·J Gene Med
2022
Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy.
Nicastro M et al.·Am J Hum Genet
2025
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