POPDC3

Chr 6AR

popeye domain cAMP effector 3

Also known as: LGMDR26, POP3, bA355M14.1

NCBI Gene: 64208ENSG00000132429UniProt: Q9HBV1

This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in these tissues during development. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal recessive 26MIM #618848
AR
0
Active trials
22
Pathogenic / LP
67
ClinVar variants
3
Pubs (1 yr)
0.7
Missense Z
0.90
LOEUF
Clinical Summary— POPDC3
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive limb-girdle muscular dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 35 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.011
Z-score 1.81
OE 0.43 (0.22–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.67Z-score
OE missense 0.85 (0.74–0.98)
133 obs / 156.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.22–0.90)
0≤0.351.4
Missense OE0.85 (0.74–0.98)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 5 / 11.7Missense obs/exp: 133 / 156.5Syn Z: -0.43
DNGOF
DN
0.7326th %ile
GOF
0.72top 25%
LOF
0.2871th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
VUS35
Likely Benign3
Benign7
22
Pathogenic
35
VUS
3
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
17
0
22
Likely Pathogenic
0
0
0
0
0
VUS
0
29
6
0
35
Likely Benign
0
1
1
1
3
Benign
0
2
3
2
7
Total13627367

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

View in ClinVar →

POPDC3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients