PALLD

Chr 4AD

palladin, cytoskeletal associated protein

Also known as: CGI-151, CGI151, MYN, PNCA1, SIH002

NCBI Gene: 23022ENSG00000129116UniProt: Q8WX93

This gene encodes a cytoskeletal protein that organizes the actin cytoskeleton and controls cell shape, adhesion, and contraction by binding to actin filaments and serving as a scaffolding molecule. Mutations cause autosomal dominant susceptibility to pancreatic cancer type 1. The gene is highly constrained against loss-of-function variants (pLI near 1.0, LOEUF 0.508), suggesting that complete loss of protein function is poorly tolerated.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Pancreatic cancer, susceptibility to, 1}MIM #606856
AD
UniProtPancreatic cancer 1
0
Active trials
10
Pubs (1 yr)
2
P/LP submissions
—
P/LP missense
0.51
LOEUF
DN
Mechanism· predicted
Clinical Summary— PALLD
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
2 unique Pathogenic / Likely Pathogenic· 329 VUS of 500 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.000
Z-score 4.56
OE 0.35 (0.24–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.88Z-score
OE missense 0.90 (0.84–0.96)
548 obs / 609.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.24–0.51)
0≤0.351.4
Missense OE0.90 (0.84–0.96)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 20 / 57.2Missense obs/exp: 548 / 609.2Syn Z: 1.01
DN
0.7230th %ile
GOF
0.6346th %ile
LOF
0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS329
Likely Benign148
Conflicting1
1
Pathogenic
1
Likely Pathogenic
329
VUS
148
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
1
0
1
VUS
12
295
20
2
329
Likely Benign
0
2
7
139
148
Benign
0
0
0
0
0
Conflicting
—1
Total1229729141480

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

View in ClinVar →

Protein Context — Lollipop Plot

PALLD · 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.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 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