PDLIM4

Chr 5AD

PDZ and LIM domain 4

Also known as: RIL

NCBI Gene: 8572ENSG00000131435UniProt: P50479

Enables alpha-actinin binding activity; protein homodimerization activity; and protein phosphatase binding activity. Involved in actin cytoskeleton organization. Located in several cellular components, including lamellipodium; perinuclear region of cytoplasm; and stress fiber. Part of filamentous actin. Implicated in osteoporosis. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

{Osteoporosis, susceptibility to}MIM #166710
AD
59
ClinVar variants
16
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PDLIM4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
16 Pathogenic / Likely Pathogenic· 37 VUS of 59 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.983
Z-score 3.26
OE 0.00 (0.00–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.71Z-score
OE missense 0.86 (0.77–0.97)
186 obs / 215.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 0 / 12.4Missense obs/exp: 186 / 215.5Syn Z: 0.53

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS37
Likely Benign6
15
Pathogenic
1
Likely Pathogenic
37
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
33
4
0
37
Likely Benign
0
4
2
0
6
Benign
0
0
0
0
0
Total03722059

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

View in ClinVar →

Protein Context — Lollipop Plot

PDLIM4 · 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

{Osteoporosis, susceptibility to}

MIM #166710

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive analysis of all evolutionary paths between two divergent PDZ domain specificities.
Teyra J et al.·Protein Sci
2020
Reduced expression of PDLIM4 gene correlates with good prognosis in acute myeloid leukemia.
Li Y et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2013
Potential drug targets for asthma identified in the plasma and brain through Mendelian randomization analysis.
Wang Y et al.·Front Immunol
2023
Single-cell RNA-seq reveals breast cancer heterogeneity and identifies TCP1 as a therapeutic target in breast cancer.
Wu H et al.·PeerJ
2025
A 4-gene signature associated with clinical outcome in high-grade gliomas.
de Tayrac M et al.·Clin Cancer Res
2011
The DNA methylome of pediatric brain tumors appears shaped by structural variation and predicts survival.
Chen F et al.·Nat Commun
2024
Cancer-associated fibroblast-derived gene signature discriminates distinct prognoses by integrated single-cell and bulk RNA-seq analyses in breast cancer.
Fang Z et al.·Aging (Albany NY)
2024
Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin.
Chen M et al.·J Biol Chem
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53.
Wang Q et al.·BMC Biol
2026🔓 Open Access
PDLIM4 drives gastric cancer malignant progression and cisplatin resistance by inhibiting HSP70 ubiquitination and degradation via competitive interaction with STUB1.
Zhu C et al.·J Nanobiotechnology
2025🔓 Open Access
Retracted: Circular RNA hsa_circ_0002360 Promotes Proliferation and Invasion and Inhibits Oxidative Stress in Gastric Cancer by Sponging miR-629-3p and Regulating the PDLIM4 Expression.
Longevity OMAC.·Oxid Med Cell Longev
2023🔓 Open Access
Circular RNA hsa_circ_0002360 Promotes Proliferation and Invasion and Inhibits Oxidative Stress in Gastric Cancer by Sponging miR-629-3p and Regulating the PDLIM4 Expression.
Yu Z et al.·Oxid Med Cell Longev
2022🔓 Open Access
PDLIM4/RIL-mediated regulation of Src and malignant properties of breast cancer cells.
Kravchenko DS et al.·Oncotarget
2020🔓 Open Access
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