PALLD

Summary

PALLD (palladin, cytoskeletal associated protein, HGNC:17068) is a protein-coding gene on chromosome 4q32.3, encoding Palladin (Q8WX93). Cytoskeletal protein required for organization of normal actin cytoskeleton.

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.

Source: NCBI Gene 23022 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pancreatic cancer, susceptibility to, 1 (Limited, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 1,743 total — 1 pathogenic
• Phenotypes (HPO): 25
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity unscored
• MANE Select transcript: NM_001166108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17068
Approved symbol	PALLD
Name	palladin, cytoskeletal associated protein
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0992, SIH002, CGI-151
Ensembl gene	ENSG00000129116
Ensembl biotype	protein_coding
OMIM	608092
Entrez	23022

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 5 retained_intron

ENST00000261509, ENST00000393726, ENST00000503290, ENST00000503457, ENST00000504519, ENST00000505667, ENST00000507325, ENST00000507699, ENST00000507735, ENST00000508898, ENST00000510998, ENST00000511611, ENST00000511682, ENST00000511948, ENST00000512127, ENST00000513187, ENST00000513245, ENST00000649826, ENST00000704822, ENST00000871520, ENST00000871521, ENST00000968439

RefSeq mRNA: 8 — MANE Select: NM_001166108 NM_001166108, NM_001166109, NM_001166110, NM_001367567, NM_001367568, NM_001367569, NM_001367570, NM_016081

CCDS: CCDS34098, CCDS54818, CCDS54819, CCDS54820, CCDS93667

Canonical transcript exons

ENST00000505667 — 22 exons

Exon	Start	End
ENSE00001291655	168925233	168925278
ENSE00001665331	168709028	168709147
ENSE00001728987	168711581	168711923
ENSE00001758511	168690603	168690744
ENSE00001766410	168685485	168685559
ENSE00001781437	168682998	168683103
ENSE00001791826	168691269	168691292
ENSE00002076303	168497052	168497194
ENSE00002084385	168926213	168928441
ENSE00003492031	168511423	168512412
ENSE00003500300	168924255	168924420
ENSE00003510328	168890922	168891057
ENSE00003524953	168668190	168668368
ENSE00003535541	168903757	168903906
ENSE00003552447	168896549	168896599
ENSE00003564455	168924945	168925078
ENSE00003589389	168681332	168681398
ENSE00003607777	168915895	168916027
ENSE00003621017	168898493	168898714
ENSE00003635840	168894579	168894677
ENSE00003653708	168921534	168921741
ENSE00003693500	168913927	168914021

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 123.3149 / max 3077.4611, expressed in 1694 samples.

FANTOM5 promoters (36 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50549	80.2561	1583
50524	9.9143	975
50552	7.9837	1461
50523	6.6585	871
50548	3.4288	1166
50504	2.6092	282
50554	1.3756	631
50521	1.2507	342
50525	0.9962	429
50529	0.9262	503

Top tissues by expression

303 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.79	gold quality
heart right ventricle	UBERON:0002080	99.68	gold quality
blood vessel layer	UBERON:0004797	99.68	gold quality
cauda epididymis	UBERON:0004360	99.66	gold quality
hair follicle	UBERON:0002073	99.65	gold quality
visceral pleura	UBERON:0002401	99.59	gold quality
seminal vesicle	UBERON:0000998	99.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.56	gold quality
lower esophagus	UBERON:0013473	99.55	gold quality
myometrium	UBERON:0001296	99.54	gold quality
right coronary artery	UBERON:0001625	99.54	gold quality
popliteal artery	UBERON:0002250	99.53	gold quality
tibial artery	UBERON:0007610	99.53	gold quality
artery	UBERON:0001637	99.50	gold quality
mucosa of stomach	UBERON:0001199	99.44	gold quality
left ventricle myocardium	UBERON:0006566	99.44	gold quality
urethra	UBERON:0000057	99.43	gold quality
body of uterus	UBERON:0009853	99.43	gold quality
aorta	UBERON:0000947	99.42	gold quality
superficial temporal artery	UBERON:0001614	99.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.37	gold quality
myocardium	UBERON:0002349	99.35	gold quality
smooth muscle tissue	UBERON:0001135	99.33	gold quality
descending thoracic aorta	UBERON:0002345	99.31	gold quality
coronary artery	UBERON:0001621	99.30	gold quality
left coronary artery	UBERON:0001626	99.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.30	gold quality
endocervix	UBERON:0000458	99.26	gold quality
thoracic aorta	UBERON:0001515	99.26	gold quality
ascending aorta	UBERON:0001496	99.24	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	914.77
E-MTAB-10287	yes	65.57
E-MTAB-8410	yes	36.92
E-GEOD-135922	yes	31.66
E-HCAD-1	yes	30.00
E-MTAB-5061	yes	26.70
E-GEOD-81547	yes	24.00
E-HCAD-31	yes	21.59
E-CURD-119	yes	19.20
E-GEOD-81608	yes	17.82
E-CURD-112	yes	14.06
E-CURD-46	yes	10.46
E-GEOD-134144	yes	8.35
E-MTAB-9388	yes	5.90
E-MTAB-11268	no	6205.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

148 targeting PALLD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-557	99.96	70.01	1640

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 39)

• Quantitative analysis of erythrocyte membrane proteins revealed decrease in palladin from patients with homozygous and heterozygous forms of beta-thalassemia. (PMID:15310273)
• Our results suggest that palladin may play an important role in recruiting profilin to sites of actin dynamics. (PMID:16367745)
• These results identify palladin 4Ig as a novel marker of myofibroblast conversion in vitro and in vivo. (PMID:16794588)
• Study identifies palladin as the mutated gene in the pancreatic cancer susceptibility locus at 4q32-34 and validates abnormal expression of the gene in a famililal pancreatic cancer kindred. (PMID:17194196)
• Palladin RNA was overexpressed in the tissues from precancerous dysplasia and pancreatic adenocarcinoma in both the familial and the sporadic disease. (PMID:17228136)
• The function of LPP and palladin is context dependent, that they play a critical role in cytoskeletal remodeling, respond to signals induced by vascular injury as well as signals that induce smooth muscle cell hypertrophy, such as angiotension II. (PMID:17322171)
• Study concludes that the P239S variant does not appear to account for a significant fraction of hereditary or early-onset pancreas cancer. (PMID:17415588)
• PALLD was differentially expressed in sclerotic hippocampi compared to non-sclerotic ones. (PMID:17515952)
• The interplay between palladin, SPIN90 and Src and characterized the role of palladin and SPIN90 in platelet derived growth factor and Src-induced cytoskeletal remodeling, was analyzed. (PMID:17537434)
• Palladin was up-regulated in adipose-derived adult stem cells during osteogenic differentiation and cyclic tensile strain. (PMID:17687002)
• palladin overexpression contributes to the invasive behavior of metastatic cells. (PMID:18978809)
• expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis. (PMID:19205907)
• Single nucleotide polymorphisms in palladin is not associated with pancreatic cancer. (PMID:19336541)
• upregulation of 85-90 kDa palladin isoform may play a role in the establishment of the tumor-associated fibroblasts phenotype, and thus in the formation of a desmoplastic tumor microenvironment (PMID:20436683)
• Akt1 phosphorylates palladin, inducing cytoskeletal reorganization and inhibiting the migration of breast cancer cells. (PMID:20471940)
• Palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma. (PMID:20811713)
• Akt signaling regulates the stability of palladin (PMID:21050850)
• The A-allele of PALLD rs7439293 was not associated with progressive carotid atherosclerosis (PMID:21054356)
• Observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC-associated stroma and stroma-dependent mechanisms affecting tumorigenesis. (PMID:21738681)
• these results suggested that palladin played a specific role in modulating the subcellular localization of the cytoplasmic ILKAP and promoting the ILKAP-induced apoptosis. (PMID:21782789)
• Palladin may identify primary pancreatic endocrine neoplasms with a propensity to metastasize to the liver (PMID:21868544)
• results indicate that palladin phosphorylation by ERK has an anti-migratory function, possibly by modulating interactions with molecules that regulate cell migration (PMID:22216253)
• A model whereby palladin-activated fibroblasts facilitate stromal-dependent metastasis and outgrowth of tumorigenic epithelium. (PMID:22291919)
• palladin functions as a dynamic scaffolding protein that promotes the assembly of dorsal stress fibers by recruiting VASP to these structures. (PMID:24496446)
• Palladin seems to regulate podosome and invodopodia formation through Rho GTPases. [Review] (PMID:24525547)
• Palladin interacts with MT1-MMP to promote tumor cell invasion in breast carcinoma. (PMID:24989798)
• Study identified the actin-associated protein palladin as a key node in signaling pathways that result in fibroblast activation in the increased tissue stiffness of a tumor microenvironment (PMID:26200861)
• Twist1 appears to require both palladin and collagen alpha1(VI) as downstream effectors for its prometastatic effects, which could be future therapeutic targets in cancer metastasis. (PMID:26973246)
• stromal palladin expression is a surrogate indicator of the treatment effect after chemoradiation therapy. (PMID:27023252)
• Palladin role in the vascular smooth muscle cell differentiation and gene expression (PMID:27088725)
• findings revealed that Palladin regulates spindle orientation and mitotic progression mainly through the AKT1-GSK3beta pathway. (PMID:28924223)
• Collectively, our results demonstrate that palladin can functionally replace the Arp2/3 complex during bacterial actin-based cellular entry and intracellular motility of Listeria monocytogenes. (PMID:29636431)
• Taken together, this study demonstrates that palladin plays an important role in themorphology and dynamic behavior of podocytes in vivo and in vitro. (PMID:29720549)
• Expression of palladin is associated with disease progression in metastatic high-grade serous carcinoma. (PMID:32741023)
• Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma. (PMID:33589694)
• PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer. (PMID:33764904)
• Palladin promotes cancer stem cell-like properties in lung cancer by activating Wnt/Beta-Catenin signaling. (PMID:36047666)
• Different Extracellular beta-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin. (PMID:36551236)
• [High expression of Circ-PALLD in heart failure is transcriptionally regulated by the transcription factor GATA4]. (PMID:37712274)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	palld	ENSDARG00000040009
mus_musculus	Palld	ENSMUSG00000058056
rattus_norvegicus	Palld	ENSRNOG00000010107
drosophila_melanogaster	bt	FBGN0005666
caenorhabditis_elegans		WBGENE00001000
caenorhabditis_elegans		WBGENE00006759

Paralogs (9): SPEG (ENSG00000072195), MYOT (ENSG00000120729), ALPK3 (ENSG00000136383), MYPN (ENSG00000138347), HMCN1 (ENSG00000143341), OBSCN (ENSG00000154358), IGFN1 (ENSG00000163395), CCDC141 (ENSG00000163492), SPEGNB (ENSG00000286095)

Protein

Protein identifiers

Palladin — Q8WX93 (reviewed: Q8WX93)

Alternative names: SIH002, Sarcoma antigen NY-SAR-77

All UniProt accessions (12): Q8WX93, A0A3B3ISX8, A0A994J7A4, B2RTX2, D6R948, D6R9F5, D6R9Z5, D6RBB1, D6RBH5, F8WA26, H0Y952, H0YA05

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with EPS8. Interacts with LASP1. Interacts with VASP. Interacts with ACTN. Interacts with SORBS2. Interacts with PFN1. Interacts with LPP. Interacts with SPIN90. Interacts with SRC. Interacts with EZR. Interacts with RAI14.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion. Myofibril. Sarcomere. Z line. Cell projection. Ruffle. Podosome. Lamellipodium. Axon. Growth cone.

Tissue specificity. Detected in both muscle and non-muscle tissues. High expression in prostate, ovary, colon, and kidney. Not detected in spleen, skeletal muscle, lung and peripheral blood lymphocytes (at protein level). Protein is overexpressed in FA6, HPAF, IMIM-PC2, SUIT-2 and PancTu-II sporadic pancreatic cancer cell lines.

Post-translational modifications. Phosphorylated predominantly on serines and, to a lesser extent, on tyrosines. Phosphorylation at Ser-1118 by PKB/AKT1 modulates cytoskeletal organization and cell motility.

Disease relevance. 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Genetic variations in PALLD may be associated with susceptibility to myocardial infarction.

Induction. Isoform 3 is expressed de novo. Isoform 4 is up-regulated by TGFB1 during myofibroblast differentiation.

Similarity. Belongs to the myotilin/palladin family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q8WX93-1	1, 200-kDa	yes
Q8WX93-2	2
Q8WX93-3	3, 140-kDa
Q8WX93-4	4, 90-kDa
Q8WX93-5	5
Q8WX93-6	6
Q8WX93-7	7
Q8WX93-8	8
Q8WX93-9	9

RefSeq proteins (8): NP_001159580, NP_001159581, NP_001159582, NP_001354496, NP_001354497, NP_001354498, NP_001354499, NP_057165 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR033017	Palladin_C	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07679

UniProt features (90 total): strand 20, modified residue 18, region of interest 16, compositionally biased region 9, splice variant 8, sequence conflict 6, domain 5, disulfide bond 3, sequence variant 2, chain 1, turn 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2DM2	SOLUTION NMR
2DM3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WX93-F1	54.74	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (18): 192, 401, 632, 635, 641, 684, 688, 728, 893, 979, 984, 1101, 1104, 1106, 1116, 1118, 1121, 1352

Disulfide bonds (3): 292–344, 462–521, 1156–1208

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 470 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_NEURON_RECOGNITION, chr4q32, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, GOCC_RUFFLE, NAGASHIMA_NRG1_SIGNALING_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506

GO Biological Process (8): keratinocyte development (GO:0003334), epithelial cell morphogenesis (GO:0003382), cytoskeleton organization (GO:0007010), homophilic cell-cell adhesion (GO:0007156), axon guidance (GO:0007411), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), dendrite self-avoidance (GO:0070593)

GO Molecular Function (6): actin binding (GO:0003779), muscle alpha-actinin binding (GO:0051371), cell-cell adhesion mediator activity (GO:0098632), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (20): stress fiber (GO:0001725), ruffle (GO:0001726), podosome (GO:0002102), nucleus (GO:0005634), mitochondrion (GO:0005739), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), lamellipodium (GO:0030027), axon (GO:0030424), growth cone (GO:0030426), excitatory synapse (GO:0060076), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell junction (GO:0030054), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
epithelial cell development	2
cell-cell adhesion	2
cell leading edge	2
plasma membrane bounded cell projection	2
intracellular membrane-bounded organelle	2
cytoplasm	2
keratinocyte differentiation	1
cell morphogenesis	1
organelle organization	1
axonogenesis	1
neuron projection guidance	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
neuron recognition	1
cytoskeletal protein binding	1
alpha-actinin binding	1
cell adhesion mediator activity	1
protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
actomyosin	1
contractile actin filament bundle	1
actin-based cell projection	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cell-substrate junction	1
cytoskeleton	1
I band	1
neuron projection	1
site of polarized growth	1
distal axon	1
synapse	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

2124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PALLD	OR13G1	Q8NGZ3	930
PALLD	TAS2R50	P59544	915
PALLD	LASP1	Q14847	871
PALLD	ROS1	P08922	839
PALLD	VASP	P50552	791
PALLD	EPS8	Q12929	789
PALLD	EZR	P15311	787
PALLD	NCKIPSD	Q9NZQ3	656
PALLD	PRSS58	Q8IYP2	626
PALLD	PALB2	Q86YC2	614
PALLD	PRSS1	P07477	601
PALLD	LPP	Q93052	598
PALLD	SRC	P12931	587
PALLD	SORBS2	O94875	585
PALLD	PFN3	P60673	573

IntAct

78 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GRPEL1	HSPA9	psi-mi:“MI:0914”(association)	0.670
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
PALLD	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.560
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
PALLD	SORBS2	psi-mi:“MI:0915”(physical association)	0.510
SORBS2	PALLD	psi-mi:“MI:0915”(physical association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PALLD	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PALLD	SRC	psi-mi:“MI:0915”(physical association)	0.400
PALLD	bipA	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
SKA3	RTL8C	psi-mi:“MI:0914”(association)	0.350
LLGL2	RBBP6	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FLNA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Mib1	TBC1D31	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
NUDCD1	DNAJB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (160): PALLD (Affinity Capture-MS), PALLD (Affinity Capture-MS), PALLD (Affinity Capture-MS), PALLD (Co-fractionation), PALLD (Affinity Capture-MS), PALLD (Biochemical Activity), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS), PALLD (Proximity Label-MS)

ESM2 similar proteins: A2A884, F1QQA8, O08696, O43151, O94993, P08651, P09414, P15822, P17923, P21999, P31629, P55200, Q00900, Q01538, Q03164, Q03172, Q08050, Q08D57, Q12857, Q1LY77, Q2M1Z3, Q3UHF7, Q3UTJ2, Q498L0, Q499E5, Q5DTJ9, Q5SW79, Q5T1R4, Q5ZKH6, Q62255, Q62417, Q66J90, Q69Z38, Q6A065, Q86V15, Q8BG87, Q8C5W0, Q8CFC2, Q8CGW4, Q8CH77

Diamond homologs: A0A087WV53, A2AAJ9, A2ASS6, A2RUH7, O75147, O94856, O94898, P05548, P52179, P54296, P97685, Q00872, Q23551, Q52KR2, Q5VST9, Q62234, Q80W87, Q810U3, Q8WX93, Q92626, A2CG49, A4IFM7, A8C984, A8X6H4, E9PT87, F1M0Z1, O02827, O14936, O43293, O44997, O49717, O54784, O60229, O70589, O75962, O80673, O88764, O94768, P07313, P08414

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AKT	unknown	PALLD	phosphorylation
AKT1	unknown	PALLD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Anchoring of the basal body to the plasma membrane	9	18.2×	6e-07
Loss of Nlp from mitotic centrosomes	6	17.0×	2e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	17.0×	2e-04
FCGR3A-mediated phagocytosis	5	16.7×	6e-04
AURKA Activation by TPX2	6	16.3×	2e-04
Recruitment of NuMA to mitotic centrosomes	7	14.6×	1e-04
Recruitment of mitotic centrosome proteins and complexes	6	14.6×	3e-04
Regulation of PLK1 Activity at G2/M Transition	6	13.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1743 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1063
Likely benign	561
Benign	63

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425779	NC_000004.11:g.(?169433478)(170523781_?)del	Pathogenic

SpliceAI

4617 predictions. Top by Δscore:

Variant	Effect	Δscore
4:168511420:CA:C	acceptor_loss	1.0000
4:168511421:A:AG	acceptor_gain	1.0000
4:168511421:A:AT	acceptor_loss	1.0000
4:168511422:G:GA	acceptor_gain	1.0000
4:168511422:GA:G	acceptor_gain	1.0000
4:168511422:GAA:G	acceptor_gain	1.0000
4:168668163:A:AG	acceptor_gain	1.0000
4:168668164:T:G	acceptor_gain	1.0000
4:168668169:T:TA	acceptor_gain	1.0000
4:168668177:ATTT:A	acceptor_gain	1.0000
4:168668177:ATTTG:A	acceptor_gain	1.0000
4:168668178:T:G	acceptor_gain	1.0000
4:168668180:T:TA	acceptor_gain	1.0000
4:168668181:G:A	acceptor_gain	1.0000
4:168668189:G:GT	acceptor_gain	1.0000
4:168668365:GAAG:G	donor_gain	1.0000
4:168681399:G:GG	donor_gain	1.0000
4:168683100:ACAG:A	donor_gain	1.0000
4:168683100:ACAGG:A	donor_loss	1.0000
4:168683101:CAG:C	donor_gain	1.0000
4:168683102:AG:A	donor_gain	1.0000
4:168683102:AGGT:A	donor_loss	1.0000
4:168683103:GG:G	donor_gain	1.0000
4:168683103:GGT:G	donor_loss	1.0000
4:168683104:G:GG	donor_gain	1.0000
4:168683104:GT:G	donor_loss	1.0000
4:168685572:G:GT	donor_gain	1.0000
4:168690593:T:A	acceptor_gain	1.0000
4:168690596:A:AG	acceptor_gain	1.0000
4:168690598:TTCA:T	acceptor_loss	1.0000

AlphaMissense

7336 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011779 (4:168593820 T>C), RS1000012307 (4:168682483 T>C), RS1000012905 (4:168656644 T>A), RS1000026303 (4:168764733 G>A), RS1000027388 (4:168768344 T>G), RS1000027507 (4:168638438 G>A,T), RS1000030131 (4:168810286 A>C,G), RS1000045053 (4:168890167 C>T), RS1000045213 (4:168794333 TCCTCTTGAGG>T), RS1000052528 (4:168609417 G>A), RS10000530 (4:168741778 T>G), RS1000053651 (4:168575336 G>A), RS1000056997 (4:168533827 A>C), RS1000058339 (4:168634716 G>A,C), RS1000059939 (4:168735325 C>T)

Disease associations

OMIM: gene MIM:608092 | disease phenotypes: MIM:606856, MIM:263520

GenCC curated gene-disease

Disease	Classification	Inheritance
pancreatic cancer, susceptibility to, 1	Limited	Autosomal dominant

Mondo (4): pancreatic adenocarcinoma (MONDO:0006047), pancreatic cancer, susceptibility to, 1 (MONDO:0011739), hereditary neoplastic syndrome (MONDO:0015356), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894)

Orphanet (2): Familial pancreatic carcinoma (Orphanet:1333), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000819	Diabetes mellitus
HP:0000952	Jaundice
HP:0001433	Hepatosplenomegaly
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0002017	Nausea and vomiting
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002254	Intermittent diarrhea
HP:0002716	Lymphadenopathy
HP:0002861	Melanoma
HP:0002896	Neoplasm of the liver
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003002	Breast carcinoma
HP:0003003	Colon cancer
HP:0003418	Back pain
HP:0004389	Intestinal pseudo-obstruction
HP:0004396	Poor appetite
HP:0005249	Functional intestinal obstruction
HP:0006725	Pancreatic adenocarcinoma
HP:0012334	Extrahepatic cholestasis
HP:0012432	Chronic fatigue
HP:0025318	Ovarian carcinoma
HP:0100592	Peritoneal abscess

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000201_1	Response to iloperidone treatment (QT prolongation)	3.000000e-06
GCST000767_2	Non-alcoholic fatty liver disease histology (AST)	6.000000e-07
GCST002793_1	Vein graft stenosis in coronary artery bypass grafting	4.000000e-06
GCST003457_2	Soluble receptor for advanced glycation end-product levels	8.000000e-07
GCST003650_6	Bacteremia	4.000000e-06
GCST004278_8	Pulse pressure	2.000000e-13
GCST005194_223	Coronary artery disease	3.000000e-08
GCST005195_98	Coronary artery disease	3.000000e-08
GCST005196_79	Coronary artery disease	3.000000e-08
GCST007096_64	Pulse pressure	6.000000e-18
GCST007267_275	Systolic blood pressure	9.000000e-10
GCST007269_231	Pulse pressure	9.000000e-18
GCST010796_3420	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010866_103	Coronary artery disease	8.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007051	vein graft stenosis
EFO:0007819	advanced glycation end-product measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

83 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	9
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	7
Tretinoin	decreases expression, increases expression	5
Valproic Acid	affects expression, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression, affects expression	3
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	decreases expression, increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
bufotalin	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
tetrahydropalmatine	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
coumarin	affects phosphorylation	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00854477	PHASE4	COMPLETED	Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
NCT01401387	PHASE4	WITHDRAWN	Pancreatic Enzyme Suppletion in Pancreatic Cancer
NCT02812992	PHASE4	COMPLETED	Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients
NCT03401827	PHASE4	UNKNOWN	The Effect of Gemcitabine Plus Nab-paclitaxel as Secondary Chemotherapy in Advanced Pancreatic Cancer
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00088894	PHASE3	COMPLETED	Gemcitabine With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT01013649	PHASE3	COMPLETED	Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery
NCT01231347	PHASE3	COMPLETED	QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas
NCT01360853	PHASE3	COMPLETED	Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer
NCT01419002	PHASE3	TERMINATED	Study to Evaluate if Neoadjuvant Radiotherapy Improves Recurrence Free Survival in Pancreatic Head Cancer
NCT01526135	PHASE3	COMPLETED	Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma
NCT01954992	PHASE3	RECRUITING	Glufosfamide Versus 5-FU in Second Line Metastatic Pancreatic Cancer
NCT02184195	PHASE3	COMPLETED	Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
NCT02436668	PHASE3	COMPLETED	Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)
NCT03126435	PHASE3	COMPLETED	EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX
NCT03377491	PHASE3	COMPLETED	Effect of Tumor Treating Fields (TTFields, 150 kHz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3)
NCT03536182	PHASE3	WITHDRAWN	Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer
NCT03649035	PHASE3	WITHDRAWN	Eus-guided Cryothermal Ablation in Stage III Pancreatic Adenocarcinoma
NCT03665441	PHASE3	COMPLETED	Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC
NCT03943667	PHASE3	COMPLETED	Gemcitabine and Paclitaxel vs Gemcitabine Alone After FOLFIRINOX Failure in Metastatic Pancreatic Ductal Adenocarcinoma
NCT04083235	PHASE3	COMPLETED	A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment
NCT04167007	PHASE3	UNKNOWN	FOLFOX vs Gemcitabine in Patients With Metastatic Pancreatic Cancer Non-fit to FOLFIRINOX
NCT04229004	PHASE3	COMPLETED	A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
NCT04617821	PHASE3	UNKNOWN	AG vs mFOLFIRINOX as Neoadjuvant Therapy for Borderline Reseactable and Locally Advanced Pancreatic Cancer
NCT04835064	PHASE3	UNKNOWN	Pancreatic Cancer With Elevated Serum CA125 Were Compared With Those Who Did Not Receive Neoadjuvant Chemotherapy.
NCT05482516	PHASE3	RECRUITING	Evaluating Novel Therapies in ctDNA Positive GI Cancers
NCT06018883	PHASE3	ACTIVE_NOT_RECRUITING	Vitamin C to Chemotherapy Related Anemia in Pancreatic Cancer
NCT06250972	PHASE3	RECRUITING	Radiotherapy to Patients With CA19-9-elevated Advanced Pancreatic Cancer
NCT06714604	PHASE3	RECRUITING	Standard or Prolonged Neoadjuvant Chemotherapy Before Surgery for BR/LAPC
NCT06861088	PHASE3	RECRUITING	The Effect of Kinisoquin™ on Thromboembolic Events in Patients With Metastatic or Locally Advanced Pancreatic Cancer
NCT06998940	PHASE3	RECRUITING	Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations
NCT07081360	PHASE3	RECRUITING	Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer
NCT07409272	PHASE3	RECRUITING	A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
NCT07491445	PHASE3	RECRUITING	Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT07562152	PHASE3	RECRUITING	Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT00020345	PHASE2	COMPLETED	Combination Chemotherapy and Radiation Therapy Plus Surgery in Treating Patients With Advanced Cancer of the Pancreas
NCT00026104	PHASE2	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With Locally Advanced Pancreatic Cancer
NCT00028834	PHASE2	COMPLETED	Bevacizumab and Gemcitabine in Treating Patients With Advanced Pancreatic Cancer
NCT00075647	PHASE2	COMPLETED	CCI-779 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT00091026	PHASE2	COMPLETED	Bevacizumab and Gemcitabine Combined With Either Cetuximab or Erlotinib in Treating Patients With Advanced Pancreatic Cancer