MRUPAV_PLIN4
- Gene
- PLIN4
- Disease
- MRUPAV
- Inheritance
- AD
- Classification
- Moderate
- Total Score
- 11
- Publications Reviewed
- 6
- Publication Span
- 5.17 years
- Last Updated
- 08/11/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Autosomal dominant MRUPAV/PLIN4-related vacuolar myopathy is caused by heterozygous coding 99-bp repeat expansions in PLIN4 within the exon encoding the amphipathic perilipin-4 domain. Reported affected families and sporadic cases show adult-onset distal and/or proximal myopathy, rimmed/autophagic vacuoles, and subsarcolemmal or cytoplasmic PLIN4/perilipin-4 aggregates that co-localize with p62/SQSTM1, FK2, NBR1, and other aggrephagy markers. Expanded alleles have been detected by PCR and long-read sequencing, with supporting linkage/segregation, absence from unaffected relatives or controls, and patient muscle studies showing expanded PLIN4 protein and aggrephagy activation.
Genetic evidence
Total: 7.5
| Singular Evidence | Probands | PMID:36151849 PMID:32451610 | 6 | PMID:36151849 reported one autosomal-dominant family and one sporadic adult-onset PLIN4-myopathy case with a heterozygous coding 99-bp PLIN4 repeat expansion and characteristic p62/perilipin-4-positive vacuolar pathology. PMID:32451610 reported a multigenerational 19p13.3-linked kindred with a PLIN4 40×99-bp expansion, absent from unaffected relatives/controls, and rimmed ubiquitin-positive autophagic vacuoles. |
| Collective Evidence | Computational | PMID:40693562 PMID:39102614 | 0 | PMID:40693562 used WES coverage and RNA-seq review as part of the workup: increased PLIN4 exon coverage suggested an expanded allele, while RNA-seq showed normal PLIN4 expression and no splicing effect; ONT sequencing confirmed the expansion. PMID:39102614 is a clinical cohort/prognostic study and does not provide TR-specific computational pathogenicity evidence. |
| Collective Evidence | Segregation | PMID:36151849 | 1.5 | PMID:36151849 reported linkage in the PLIN4-related family to a 3.39 Mb 19p13.3 candidate interval (chr19:2635061–6033965) with maximum LOD 3.0408; PCR showed the expanded PLIN4 band in affected individuals and only the wild-type band in unaffected relatives. |
Experimental evidence
Total: 3.5
| Function | Biochemical function | PMID:40693562 | 0.5 | PMID:40693562 showed increased PLIN4 at the sarcolemma/vacuoles in patient muscle and discussed that PLIN4 repeat expansion may alter lipid-droplet membrane-binding specificity, promoting abnormal sarcolemmal targeting and aggregation of perilipin-4. |
| Function | Protein interaction | PMID:35499779 PMID:40693562 | 1.5 | PMID:35499779 showed patient muscle perilipin-4 co-localized with FK2, p62/SQSTM1, NBR1, and LC3B in vacuoles/subsarcolemma, consistent with aggrephagy-related aggregation. PMID:40693562 similarly showed PLIN4 co-localization with p62 and NBR1 at sarcolemma/vacuoles and detected a higher-molecular-weight PLIN4 band from the expanded allele by western blot. |
| Function | Regulatory impact | PMID:40693562 | 0.5 | PMID:40693562 reported patient muscle RNA-seq with normal PLIN4 mRNA expression and no observed PLIN4 splicing effect. Western blot revealed increased PLIN4 protein expression in patients compared with controls. |
| Functional Alteration | Patient cells | PMID:37145156 | 1 | PMID:37145156 reported patient muscle biopsy findings in affected PLIN4 expansion carriers, including rimmed vacuoles and PLIN4, FK2, p62/SQSTM1, and NBR1 positivity/accumulation in muscle fibers; biopsies were abnormal even in some minimally symptomatic carriers. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.