POPDC3

Chr 6AR

popeye domain cAMP effector 3

Also known as: LGMDR26, POP3, bA355M14.1

NCBI Gene: 64208 ENSG00000132429 UniProt: Q9HBV1 OMIM: 605824

This protein contains three transmembrane domains and functions in maintaining heart function through cAMP-binding, with expression in cardiac and skeletal muscle during development. Mutations cause limb-girdle muscular dystrophy type 26, an autosomal recessive disorder affecting both cardiac and skeletal muscle systems. The gene shows low constraint to loss-of-function variants (pLI 0.01, LOEUF 0.90), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal recessive 26MIM #618848

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · autosomal recessive limb-girdle muscular dystrophy · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.43 (0.22–0.90)

0≤0.351.4

Missense OE?0.85 (0.74–0.98)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 5 / 11.7Missense obs/exp: 133 / 156.5Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in POPDC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

347 rare PASS variants

Rare truncating (LoF)

1 in 2,000

49 rare PASS variants

Rare synonymous (reference)

1 in 750

126 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POPDC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 370	1 in 2,700
South Asian	~43k	1 in 200	1 in 570
Remaining (unassigned)	~30k	1 in 250	1 in 1,900
European (Finnish)	~27k	1 in 780	≈ 1 in 6,700
Admixed American	~22k	1 in 160	1 in 3,200
African / African American	~21k	1 in 210	1 in 860
East Asian	~20k	1 in 230	1 in 880
Ashkenazi Jewish	~13k	1 in 270	1 in 1,000
Middle Eastern	~2,884	1 in 320	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.