PALLD
protein-codingpalladin, cytoskeletal associated protein, the group of I-set domain containing
Gene summary
This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~431.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011739
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Oncologic
Intervention: Oncologic
Rationale: Individuals are reported to be at increased risk of pancreatic cancer, and awareness may allow early diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PALLD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001166108.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 586 | 2 | 596 | ||
| missense | 1245 | 53 | 1 | 1299 | ||
| nonsense | 3 | 2 | 5 | |||
| start loss | 0 | |||||
| frameshift | 7 | 7 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 1268 | 641 | 3 | 1912 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001159580.1 | 20 | MANE Select | |
| Ensembl | ENSP00000425556.1 | 20 | MANE Select | |
| RefSeq | NP_001159581.1 | 17 | Standard | |
| RefSeq | NP_001159582.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- keratinocyte development
- epithelial cell morphogenesis
- cytoskeleton organization
- homophilic cell adhesion via plasma membrane adhesion molecules
- axon guidance
Molecular Function
- actin binding
- protein binding
- muscle alpha-actinin binding
- cell-cell adhesion mediator activity
Cellular Component
- ruffle
- podosome
- nucleus
- cytosol
- actin filament
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000505667
- Coding exons
- 20
- Length
- 431392
- Individuals with no LoFs
- 125592
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 156
- Defined
- 125748
- p
- 0.000620
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.881 | 548 | 609 | 0.899 | 0.0000339 | 7305 |
| Missense (PolyPhen) | 165 | 217.84 | 0.75745 | 2568 | ||
| Synonymous | 1.01 | 205 | 224 | 0.915 | 0.0000128 | 2246 |
| Loss of Function | 4.56 | 20 | 57.2 | 0.349 | 0.00000352 | 652 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00080 | 0.00080 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00043 | 0.00044 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00050 | 0.00049 | rare |
| South Asian | 0.0020 | 0.0020 | notable |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytoskeletal protein required for organization of normal actin cytoskeleton. Roles in establishing cell morphology, motility, cell adhesion and cell-extracellular matrix interactions in a variety of cell types. May function as a scaffolding molecule with the potential to influence both actin polymerization and the assembly of existing actin filaments into higher-order arrays. Binds to proteins that bind to either monomeric or filamentous actin. Localizes at sites where active actin remodeling takes place, such as lamellipodia and membrane ruffles. Different isoforms may have functional differences. Involved in the control of morphological and cytoskeletal changes associated with dendritic cell maturation. Involved in targeting ACTN to specific subcellular foci. {ECO:0000269|PubMed:11598191, ECO:0000269|PubMed:15147863, ECO:0000269|PubMed:17537434}.;
- Disease
- DISEASE: Pancreatic cancer 1 (PNCA1) [MIM:606856]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269|PubMed:17194196, ECO:0000269|PubMed:17415588, ECO:0000269|PubMed:17455999}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Genetic variations in PALLD may be associated with susceptibility to myocardial infarction. {ECO:0000269|PubMed:16175505}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.923
- RVIS EVS
- 0.14
- RVIS percentile EVS
- 63.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |