PDLIM2

Chr 8

PDZ and LIM domain 2

Also known as: MYSTIQUE, SLIM

NCBI Gene: 64236ENSG00000120913UniProt: Q96JY6

The protein functions as an adapter at the actin cytoskeleton that promotes cell attachment and is necessary for epithelial cell migration. Mutations in this gene cause autosomal dominant myopathy with rimmed vacuoles and other muscle disorders. The gene shows low constraint against loss-of-function variants, suggesting tolerance to protein reduction.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
11
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.84
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PDLIM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 146 VUS of 259 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.09
OE 0.48 (0.29–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.09Z-score
OE missense 0.98 (0.89–1.09)
259 obs / 263.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.29–0.84)
0≤0.351.4
Missense OE0.98 (0.89–1.09)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 9 / 18.8Missense obs/exp: 259 / 263.0Syn Z: -0.67
DN
0.76top 25%
GOF
0.73top 25%
LOF
0.3452th %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

259 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS146
Likely Benign11
79
Pathogenic
4
Likely Pathogenic
146
VUS
11
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
0
140
6
0
146
Likely Benign
0
10
1
0
11
Benign
0
0
0
0
0
Total0150900240

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

View in ClinVar →

Protein Context — Lollipop Plot

PDLIM2 · 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
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 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
Loss of the PDLIM2 protein during chronic colitis promotes inflammation, impaired epithelium recovery, alterations to the microbiome and oxidative stress.
Ward S et al.·Front Endocrinol (Lausanne)
2025Open Access
PDLIM2 deficiency mediated by PBXIP1 promotes the proliferation of HCC cells through reducing the polyubiquitination and degradation of TRIM27.
Zhang X et al.·Eur J Med Res
2025Open Access
Myeloid PDLIM2 repression as a common mechanism of infection susceptibility in lung diseases.
Gao F et al.·Front Immunol
2025Open AccessFunctional
Beyond structural domains: the emerging roles of PDLIM2 in cellular signaling and cancer progression.
Shi Y et al.·Front Physiol
2025Open Access
The ubiquitination degradation of KLF15 mediated by WSB2 promotes lipogenesis and progression of hepatocellular carcinoma via inhibiting PDLIM2 expression.
Chen J et al.·J Gastroenterol Hepatol
2025
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