PALLD

palladin, cytoskeletal associated protein, the group of I-set domain containing

Basic information

Region (hg38): 4:168497052-168928457

Links

ENSG00000129116 ∙ NCBI:23022 ∙ OMIM:608092 ∙ HGNC:17068 ∙ Uniprot:Q8WX93 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pancreatic cancer, susceptibility to, 1 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatic cancer, susceptibility to, 1	AD	Oncologic	Individuals are reported to be at increased risk of pancreatic cancer, and awareness may allow early diagnosis and management	Oncologic	17194196

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PALLD gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PALLD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	545	11	561
missense			1057	28	9	1094
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel			20	1	4	25
splice donor/acceptor (+/-2bp)						0
splice region			12	23	3	38
non coding			33	35	65	133
Total	0	0	1119	609	89

Variants in PALLD

This is a list of pathogenic ClinVar variants found in the PALLD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-168497098-G-C		Pancreatic cancer, susceptibility to, 1	Benign (Jan 13, 2018)
4-168497099-G-A		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 13, 2018)
4-168497105-C-A		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 12, 2018)
4-168497115-C-T		Pancreatic cancer, susceptibility to, 1	Benign (Jan 13, 2018)
4-168497116-A-T		Pancreatic cancer, susceptibility to, 1	Benign (Jan 12, 2018)
4-168497134-A-G		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 13, 2018)
4-168497138-G-T		Carcinoma of pancreas	Uncertain significance (Jun 14, 2016)
4-168497142-A-G		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 13, 2018)
4-168497162-C-G		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 12, 2018)
4-168497202-A-G		not specified • Pancreatic cancer, susceptibility to, 1	Benign (Jan 12, 2018)
4-168497203-G-A		Pancreatic cancer, susceptibility to, 1	Uncertain significance (Jan 13, 2018)
4-168497248-TA-T			Benign (Aug 30, 2019)
4-168497281-T-C			Benign (Jun 23, 2018)
4-168511112-C-CA			Benign (Jun 19, 2021)
4-168511143-C-T			Benign (Jun 19, 2021)
4-168511192-T-C			Benign (Jun 19, 2021)
4-168511315-CTT-C			Benign (Jun 23, 2018)
4-168511497-G-A		Pancreatic cancer, susceptibility to, 1	Benign/Likely benign (Jul 07, 2023)
4-168511510-A-G		not specified	Likely benign (Aug 13, 2022)
4-168511510-A-T		not specified	Likely benign (Dec 31, 2020)
4-168511512-G-T		Pancreatic cancer, susceptibility to, 1 • PALLD-related disorder • not specified	Benign/Likely benign (Sep 04, 2022)
4-168511515-C-T		not specified	Uncertain significance (Dec 16, 2022)
4-168511516-C-T		not specified	Likely benign (Dec 13, 2019)
4-168511518-C-A		not specified	Uncertain significance (Dec 15, 2022)
4-168511518-C-T		not specified	Uncertain significance (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PALLD	protein_coding	protein_coding	ENST00000505667	20	431392

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000525	1.00	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.881	548	609	0.899	0.0000339	7305
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000948	0.000945
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000505	0.000492
Middle Eastern	0.000435	0.000435
South Asian	0.00203	0.00203
Other	0.000822	0.000815

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.280
• hipred: Y
• hipred_score: 0.705
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Palld
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: keratinocyte development;epithelial cell morphogenesis;cytoskeleton organization;homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;cell migration;actin cytoskeleton organization;dendrite self-avoidance
• Cellular component: ruffle;podosome;nucleus;cytosol;actin filament;plasma membrane;focal adhesion;actin cytoskeleton;Z disc;lamellipodium;axon;growth cone
• Molecular function: actin binding;protein binding;muscle alpha-actinin binding;cell-cell adhesion mediator activity