PARD3

Summary

PARD3 (par-3 family cell polarity regulator, HGNC:16051) is a protein-coding gene on chromosome 10p11.22-p11.21, encoding Partitioning defective 3 homolog (Q8TEW0). Adapter protein involved in asymmetrical cell division and cell polarization processes.

This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 56288 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 290 total — 3 pathogenic
• MANE Select transcript: NM_001184785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16051
Approved symbol	PARD3
Name	par-3 family cell polarity regulator
Location	10p11.22-p11.21
Locus type	gene with protein product
Status	Approved
Aliases	PARD-3, PAR-3, PAR3, PARD3A, Bazooka, Baz, ASIP, PPP1R118
Ensembl gene	ENSG00000148498
Ensembl biotype	protein_coding
OMIM	606745
Entrez	56288

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 62 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000340077, ENST00000346874, ENST00000350537, ENST00000374768, ENST00000374773, ENST00000374776, ENST00000374788, ENST00000374789, ENST00000374790, ENST00000374794, ENST00000466092, ENST00000544292, ENST00000545260, ENST00000545693, ENST00000651752, ENST00000696673, ENST00000858358, ENST00000926299, ENST00000926300, ENST00000926301, ENST00000926302, ENST00000926303, ENST00000926304, ENST00000926305, ENST00000926306, ENST00000926307, ENST00000926308, ENST00000926311, ENST00000926312, ENST00000926313, ENST00000926314, ENST00000926315, ENST00000926316, ENST00000926317, ENST00000926318, ENST00000926319, ENST00000926320, ENST00000926321, ENST00000926322, ENST00000926323, ENST00000926324, ENST00000926325, ENST00000926326, ENST00000926327, ENST00000926328, ENST00000926329, ENST00000926330, ENST00000926331, ENST00000926332, ENST00000926333, ENST00000926334, ENST00000963004, ENST00000963005, ENST00000963006, ENST00000963007, ENST00000963008, ENST00000963009, ENST00000963010, ENST00000963011, ENST00000963012, ENST00000963013, ENST00000963014, ENST00000963015, ENST00000963016

RefSeq mRNA: 11 — MANE Select: NM_001184785 NM_001184785, NM_001184786, NM_001184787, NM_001184788, NM_001184789, NM_001184790, NM_001184791, NM_001184792, NM_001184793, NM_001184794, NM_019619

CCDS: CCDS53509, CCDS53510, CCDS53511, CCDS53512, CCDS53513, CCDS53514, CCDS53515, CCDS53516, CCDS7178

Canonical transcript exons

ENST00000374788 — 25 exons

Exon	Start	End
ENSE00000985594	34450317	34450448
ENSE00000985597	34384129	34384254
ENSE00000985598	34382540	34382922
ENSE00000985599	34377967	34378106
ENSE00000985601	34360071	34360259
ENSE00000985602	34359147	34359317
ENSE00000985604	34341627	34341816
ENSE00000985605	34337275	34337426
ENSE00000985611	34374874	34375002
ENSE00000993106	34269657	34269899
ENSE00000993108	34372498	34372536
ENSE00001093082	34119613	34119740
ENSE00001191643	34347965	34348115
ENSE00001216646	34336199	34336243
ENSE00001216763	34470085	34470263
ENSE00001345898	34131463	34131583
ENSE00001345968	34516979	34517159
ENSE00001345976	34696318	34696419
ENSE00001413755	34109561	34111562
ENSE00001464703	34814876	34815296
ENSE00003488500	34331117	34331344
ENSE00003602004	34401826	34401917
ENSE00003604932	34399330	34399413
ENSE00003627522	34317107	34317338
ENSE00003694214	34284135	34284245

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9052 / max 119.8711, expressed in 1540 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109094	16.8514	1540
109093	0.0538	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	97.82	silver quality
tongue squamous epithelium	UBERON:0006919	96.95	gold quality
secondary oocyte	CL:0000655	96.27	gold quality
skin of abdomen	UBERON:0001416	95.83	gold quality
skin of leg	UBERON:0001511	95.45	gold quality
buccal mucosa cell	CL:0002336	94.98	gold quality
lower esophagus mucosa	UBERON:0035834	94.93	gold quality
esophagus mucosa	UBERON:0002469	94.84	gold quality
zone of skin	UBERON:0000014	94.80	gold quality
oocyte	CL:0000023	94.79	gold quality
gingival epithelium	UBERON:0001949	94.63	gold quality
nipple	UBERON:0002030	94.60	gold quality
cervix epithelium	UBERON:0004801	94.59	gold quality
adrenal tissue	UBERON:0018303	94.44	gold quality
esophagus	UBERON:0001043	94.37	gold quality
pharyngeal mucosa	UBERON:0000355	94.25	gold quality
squamous epithelium	UBERON:0006914	94.20	gold quality
calcaneal tendon	UBERON:0003701	94.17	gold quality
medial globus pallidus	UBERON:0002477	94.02	gold quality
mucosa of stomach	UBERON:0001199	93.99	gold quality
tendon	UBERON:0000043	93.98	gold quality
gingiva	UBERON:0001828	93.98	gold quality
sural nerve	UBERON:0015488	93.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.66	gold quality
lower esophagus	UBERON:0013473	93.65	gold quality
gluteal muscle	UBERON:0002000	93.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.39	gold quality
left ovary	UBERON:0002119	93.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.23	gold quality
islet of Langerhans	UBERON:0000006	93.17	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	2975.43
E-HCAD-35	yes	1403.90
E-CURD-119	yes	26.29
E-HCAD-25	yes	24.29
E-ANND-3	yes	10.77
E-ANND-2	no	1436.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting PARD3, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-219A-5P	99.91	73.36	735

Literature-anchored findings (GeneRIF, showing 40)

• findings demonstrated that G-protein-activated phospholipase C-beta interacts with cell polarity proteins Par3 and Par6 to form protein complexes and to mediate downstream signal transduction (PMID:15782111)
• fine-tuning mechanism of Par3 in epithelial tight junction assembly controlled by the EGF receptor-SFK signaling pathway. (PMID:17053785)
• We provide evidence for the existence of a distinct PAR protein complex in endothelial cells. Both PAR-3 and PAR-6 associate directly with the adherens junction protein vascular endothelial cadherin (VE-cadherin). (PMID:17057644)
• Par3 is a novel component of the DNA-PK complex that implicates an unexpected link of cell polarity to double-strand DNA break repair. (PMID:17287830)
• Because Numb interacts with the aPKC binding partner PAR-3, we propose a model in which polarized Numb phosphorylation contributes to cell migration by directing integrin endocytosis to the leading edge (PMID:17609107)
• Two polarity proteins, Par3 and Par6, are also required for EC lumen and tube formation, as they establish EC polarity through their association with Cdc42 and atypical PKC. (PMID:18319301)
• Neph1-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity (PMID:18562307)
• identified 10 potential novel binding proteins of PDZ domains of Par3 in Jurkat cells (PMID:18685789)
• Results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC. (PMID:19503097)
• Cell polarity factor Par3 binds SPTLC1 and modulates monocyte serine palmitoyltransferase activity and chemotaxis (PMID:19592499)
• Pard-3 and AS3 genes are mutationally inactivated in prostate cancer cells. (PMID:19737411)
• Data show that Aurora A interacts directly with the atypical protein kinase C binding domain of Par3 and phosphorylates it at serine 962. (PMID:19812038)
• The results suggest that Par3 directly interacts with FAK and PI3-kinase, enhancing their activities for polarized cell migration. (PMID:20191563)
• Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. (PMID:20933426)
• Factors-derived from preeclapsia placentas not only interrupt junction protein VE-cadherin distribution, but also perturb polarity protein PARD-3 expression and distribution in vascular endothelium (PMID:20959641)
• Data show that DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. (PMID:21170030)
• there was no association of MAGI2 and PARD3 with IBD. (PMID:21515326)
• Data indicate that both tumor focality and Par3/Par6/atypical protein kinase C (APKC) expression were significantly associated with tumor recurrence. (PMID:21549621)
• Changes in cell polarity proteins Par-3 and PP-1 are associated with altered expression and assembly of tight junction proteins claudin-2, -3, -5 and -7 and ZO-1, causing paracellular leakage in active coeliac disease. (PMID:21865402)
• A VE-cadherin-PAR3-alpha-catenin complex regulates the Golgi localization and activity of cytosolic phospholipase A(2)alpha in endothelial cells.( (PMID:22398721)
• genetic association studies in a Chinese Han population: Data suggest that 6 SNPs in PARD3 (rs2496720, rs2252655, rs3851068, rs118153230, rs10827337, rs12218196) are associated with neural tube defects/anencephaly in this population. (PMID:22447895)
• The scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. (PMID:22883624)
• Par3 is identified as a regulator of signaling pathways relevant to invasive breast cancer. (PMID:23153534)
• Suggest that loss of Par3 promotes metastatic behaviour of ErbB2-induced breast tumour epithelial cells by decreasing cell-cell cohesion. (PMID:23263278)
• Data show that increased partitioning defective 3 (Par-3) expression is associated with distant metastasis and poor survival rates in patients with hepatocellular carcinoma (HCC). (PMID:23322019)
• Our results suggest that PAR-3 has a role in the clinical aggressiveness of cell Renal Cell Carcinoma (PMID:24136590)
• The PAR polarity complex of PARD3, PARD6, and an atypical protein kinase C (aPKC) regulate several aspects of neuronal migration.[review] (PMID:24243103)
• A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in clear cell renal cell carcinoma and could be useful to identify patients with high-risk tumors. (PMID:24856572)
• PAR3 and aPKC control the organization of the Golgi through CLASP2 phosphorylation. (PMID:25518939)
• Par-3 plays an important role in the modulation of intestinal barrier function by regulating delivery of occludin as well as suppression of MLC phosphorylation. (PMID:25820151)
• PAR3-mutant proteins exhibit a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions and activate STAT3 at cell confluence. (PMID:25833829)
• Shp2 promotes metastasis of prostate cancer by attenuating the PAR3/PAR6/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition (PMID:26050620)
• Taken together, these results suggest that the Par3 regulates invasion and metastasis in pancreatic cancers by controlling tight junction assembly via Tiam1. (PMID:26084985)
• study indicated a potential molecular basis for cell growth-promoting function of PARD3 by modulating the Hippo pathway signaling in response to cell contact and cell polarity signals (PMID:26116754)
• Knockdown of the polarity protein Par3 reversed the effects of Galpha13 knockdown on cell-cell adhesion and proteolytic invasion in three-dimensional collagen. (PMID:26589794)
• These results demonstrate the importance of Par3 and SNAIL in development of KSHV-induced B-cells cancers (PMID:27463802)
• Loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3zeta protein. (PMID:27588399)
• We first demonstrate that Hook2 is essential for the polarized Golgi re-orientation towards the migration front. Depletion of Hook2 results in a decrease of PAR6alpha at the centrosome during cell migration, while overexpression of Hook2 in cells induced the formation of aggresomes with the recruitment of PAR6alpha, aPKC and PAR3 (PMID:27624926)
• Results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis, probably through modulating IL-6 /STAT3 signaling. (PMID:27855669)
• Studies suggest that rare deleterious variants of PARD3 in the aPKC-binding region contribute to human cranial neural tube defect (NTD). (PMID:27925688)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pard3ab	ENSDARG00000010583
danio_rerio	PARD3	ENSDARG00000110804
mus_musculus	Pard3	ENSMUSG00000025812
rattus_norvegicus	Pard3	ENSRNOG00000032437
drosophila_melanogaster	baz	FBGN0000163
caenorhabditis_elegans		WBGENE00003918

Paralogs (1): PARD3B (ENSG00000116117)

Protein

Protein identifiers

Partitioning defective 3 homolog — Q8TEW0 (reviewed: Q8TEW0)

Alternative names: Atypical PKC isotype-specific-interacting protein, CTCL tumor antigen se2-5, PAR3-alpha

All UniProt accessions (6): Q8TEW0, A0A8Q3WLH5, B1AP52, F5GZI3, Q5VWU8, Q5VWV2

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Targets the phosphatase PTEN to cell junctions. Involved in Schwann cell peripheral myelination. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons.

Subunit / interactions. Interacts (via PDZ 1 domain) with F11R/JAM1, PARD6A and PARD6B. Interacts with PRCKI and CDH5. Interacts (via PDZ 3 domain) with PTEN (via C-terminus). Part of a complex with PARD6A or PARD6B, PRKCI or PRKCZ and CDC42 or RAC1. Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with LIMK2, AURKA and AURKB. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Directly interacts with TIAM1 and TIAM2. Interacts with ECT2, FBF1 and SIRT2. Interacts (via coiled-coil domain) with FRMD4A. Found in a complex with PARD3, CYTH1 and FRMD4A. Interacts with SAPCD2. Interacts with PRKCA. Interacts with PRKCZ.

Subcellular location. Cytoplasm. Endomembrane system. Cell junction. Tight junction. Adherens junction. Cell membrane. Cell cortex. Cytoskeleton.

Tissue specificity. Widely expressed.

Post-translational modifications. Acetylated. Deacetylated by SIRT2, thereby inhibiting Schwann cell peripheral myelination. Phosphorylation at Ser-827 by PRKCZ and PRKCI occurs at the most apical tip of epithelial cell-cell contacts during the initial phase of tight junction formation and may promote dissociation of the complex with PARD6. EGF-induced Tyr-1127 phosphorylation mediates dissociation from LIMK2. Phosphorylation by AURKA at Ser-962 is required for the normal establishment of neuronal polarity.

Disease relevance. Neural tube defects (NTD) [MIM:182940] Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization. The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids.

Miscellaneous. Antibodies against PARD3 are present in sera from patients with cutaneous T-cell lymphomas.

Similarity. Belongs to the PAR3 family.

Isoforms (11)

UniProt ID	Names	Canonical?
Q8TEW0-1	1, A	yes
Q8TEW0-2	2, B, La
Q8TEW0-3	3, C
Q8TEW0-4	4, D
Q8TEW0-5	5, E
Q8TEW0-6	6, F
Q8TEW0-7	7, Lb
Q8TEW0-8	8, Sa
Q8TEW0-9	9, Sb
Q8TEW0-10	10
Q8TEW0-11	11

RefSeq proteins (11): NP_001171714, NP_001171715, NP_001171716, NP_001171717, NP_001171718, NP_001171719, NP_001171720, NP_001171721, NP_001171722, NP_001171723, NP_062565 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR021922	Par3/HAL_N	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR052213	PAR3	Family

Pfam: PF00595, PF12053

UniProt features (86 total): modified residue 24, compositionally biased region 16, splice variant 10, region of interest 8, strand 6, sequence variant 5, sequence conflict 5, coiled-coil region 4, domain 3, mutagenesis site 2, helix 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KOM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEW0-F1	54.37	0.15

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 (24): 25, 91, 156, 174, 383, 489, 692, 695, 715, 728, 809, 827, 834, 837, 851, 852, 873, 885, 962, 971 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
962	abolishes phosphorylation by aurka.
1127	delayed epithelial tight junction assembly.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 289 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_92, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_PHOSPHORYLATION, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_VESICLE_ORGANIZATION, WANG_RECURRENT_LIVER_CANCER_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_APICAL_JUNCTION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_GLIAL_CELL_DEVELOPMENT

GO Biological Process (19): microtubule cytoskeleton organization (GO:0000226), protein targeting to membrane (GO:0006612), cell adhesion (GO:0007155), establishment or maintenance of cell polarity (GO:0007163), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), axonogenesis (GO:0007409), intracellular protein localization (GO:0008104), asymmetric cell division (GO:0008356), negative regulation of peptidyl-threonine phosphorylation (GO:0010801), myelination in peripheral nervous system (GO:0022011), establishment of cell polarity (GO:0030010), positive regulation of myelination (GO:0031643), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), establishment of centrosome localization (GO:0051660), protein-containing complex assembly (GO:0065003), bicellular tight junction assembly (GO:0070830), establishment of epithelial cell polarity (GO:0090162), cell differentiation (GO:0030154), cell division (GO:0051301)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (17): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), bicellular tight junction (GO:0005923), cell cortex (GO:0005938), endomembrane system (GO:0012505), apical plasma membrane (GO:0016324), cell junction (GO:0030054), internode region of axon (GO:0033269), apical junction complex (GO:0043296), tight junction (GO:0070160), PAR polarity complex (GO:0120157), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by TGF-beta Receptor Complex	1
Cell-cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular process	3
phosphatidylinositol phosphate binding	3
cell-cell junction	3
myelination	2
anion binding	2
binding	2
cytoplasm	2
cell periphery	2
cytoskeleton organization	1
microtubule-based process	1
protein targeting	1
establishment of protein localization to membrane	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
macromolecule localization	1
cell division	1
negative regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
establishment or maintenance of cell polarity	1
regulation of myelination	1
positive regulation of nervous system process	1
positive regulation of cellular process	1
establishment or maintenance of apical/basal cell polarity	1
centrosome localization	1
establishment of localization in cell	1
establishment of organelle localization	1
cellular component assembly	1
protein-containing complex organization	1
apical junction assembly	1
tight junction assembly	1
establishment of cell polarity	1
cellular developmental process	1
phosphatidylinositol bisphosphate binding	1

Protein interactions and networks

STRING

2010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARD3	CDC42	P21181	995
PARD3	PRKCZ	Q05513	992
PARD3	PARD6A	Q9NPB6	991
PARD3	PALS1	Q8N3R9	969
PARD3	PARD6B	Q9BYG5	896
PARD3	PARD6G	Q9BYG4	892
PARD3	PRKCI	P41743	883
PARD3	AMOT	Q4VCS5	839
PARD3	TIAM1	Q13009	835
PARD3	ARHGAP17	Q68EM7	807
PARD3	F11R	Q9Y624	804
PARD3	GPSM2	P81274	798
PARD3	NECTIN1	Q15223	757
PARD3	TJP1	Q07157	739
PARD3	PATJ	Q8NI35	736

IntAct

592 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
YWHAZ	PARD3	psi-mi:“MI:0915”(physical association)	0.880
PARD3	YWHAH	psi-mi:“MI:0915”(physical association)	0.870
YWHAH	PARD3	psi-mi:“MI:0915”(physical association)	0.870
YWHAH	TSC2	psi-mi:“MI:0914”(association)	0.850
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
PARD6A	PARD3	psi-mi:“MI:0915”(physical association)	0.810
PARD3	PARD6A	psi-mi:“MI:0915”(physical association)	0.810
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
PARD6G	PRKCI	psi-mi:“MI:0914”(association)	0.720
PARD6B	PARD3	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PARD3	CTNNB1	psi-mi:“MI:2364”(proximity)	0.690
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
PARD3	PRKCI	psi-mi:“MI:0914”(association)	0.620
PARD3	PRKCI	psi-mi:“MI:0915”(physical association)	0.620
PRKCI	PARD3	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (432): PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), PARD3 (Reconstituted Complex), PARD3 (Reconstituted Complex), PARD3 (Reconstituted Complex), PARD3 (Reconstituted Complex), PARD3 (Reconstituted Complex), PARD3 (Proximity Label-MS), PARD3 (Proximity Label-MS), PARD3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G4, D3YZU1, E9Q9R9, F1MAD2, O15018, O35346, O35867, O60759, P34152, P97306, P97879, Q00944, Q4L1J4, Q5F488, Q5I0L6, Q5JV73, Q5RD32, Q5SGD7, Q5TCQ9, Q68DX3, Q69Z98, Q6DD51, Q6P9H4, Q6RHR9, Q6ZWJ1, Q812E4, Q8BH60, Q8BMA3, Q8IWQ3, Q8TDM6, Q8TDW5, Q8TEW0, Q8TEW8, Q91VY6, Q925T6, Q96QZ7, Q99469, Q99NH2, Q9CSB4, Q9EQJ9

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, B4F7E7, D3ZAA9, E2QY99, E2QYC9, E7FDW2, F1MAD2, G5ECY0, O14910, O15018, O55164, O75970, O84033, O88382, O88951, O88952, P15454, P31006, P31007, P31016, P46195, P57105, P68907, P70175, P78352, P93757, Q0P5F3, Q0SS73, Q0TPK6, Q12959, Q13425, Q13884, Q14160, Q15700, Q16774, Q24210, Q255A8, Q28C55, Q2KIB6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AURKA	up-regulates	PARD3	phosphorylation
MARK2	up-regulates	PARD3	phosphorylation
PRKCZ	up-regulates	PARD3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 155 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
Activation of BAD and translocation to mitochondria	7	48.9×	8e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	43.1×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	43.1×	1e-08
Activation of BH3-only proteins	8	36.4×	8e-09
Signaling by Hippo	5	24.9×	4e-05
RHO GTPases activate PKNs	8	23.3×	1e-07
Intrinsic Pathway for Apoptosis	8	21.5×	2e-07
EPHA-mediated growth cone collapse	6	20.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	5	21.2×	3e-03
establishment or maintenance of cell polarity	5	14.6×	8e-03
negative regulation of TORC1 signaling	6	14.2×	3e-03
protein targeting	5	13.4×	8e-03
ephrin receptor signaling pathway	5	12.6×	9e-03
intracellular protein localization	8	6.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	181
Likely benign	33
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
254185	NM_001184785.2(PARD3):c.2729C>A (p.Pro910Gln)	Pathogenic
254187	NM_001184785.2(PARD3):c.2339A>G (p.Asp780Gly)	Pathogenic
254190	NC_000010.10:g.34835589_34975192del139604	Pathogenic

SpliceAI

10078 predictions. Top by Δscore:

Variant	Effect	Δscore
10:34111560:TGC:T	acceptor_gain	1.0000
10:34111563:C:CC	acceptor_gain	1.0000
10:34119604:T:TA	donor_gain	1.0000
10:34119736:TTCGG:T	acceptor_gain	1.0000
10:34119737:TCGG:T	acceptor_gain	1.0000
10:34119738:CGG:C	acceptor_gain	1.0000
10:34119738:CGGC:C	acceptor_gain	1.0000
10:34119739:GG:G	acceptor_gain	1.0000
10:34119739:GGCTG:G	acceptor_loss	1.0000
10:34119741:C:CC	acceptor_gain	1.0000
10:34119741:CTG:C	acceptor_loss	1.0000
10:34131458:CTT:C	donor_loss	1.0000
10:34131459:TTA:T	donor_loss	1.0000
10:34131460:T:TG	donor_loss	1.0000
10:34131461:A:AC	donor_gain	1.0000
10:34131461:A:AT	donor_loss	1.0000
10:34131461:AC:A	donor_gain	1.0000
10:34131461:ACC:A	donor_gain	1.0000
10:34131462:C:CT	donor_gain	1.0000
10:34131462:CC:C	donor_gain	1.0000
10:34131462:CCC:C	donor_gain	1.0000
10:34131462:CCCA:C	donor_gain	1.0000
10:34131462:CCCAG:C	donor_gain	1.0000
10:34131579:TGTTA:T	acceptor_gain	1.0000
10:34131580:GTTA:G	acceptor_gain	1.0000
10:34131581:TTA:T	acceptor_gain	1.0000
10:34131582:TA:T	acceptor_gain	1.0000
10:34131584:C:CC	acceptor_gain	1.0000
10:34269899:CCTA:C	acceptor_gain	1.0000
10:34269900:C:CC	acceptor_gain	1.0000

AlphaMissense

8967 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:34331173:A:T	I929N	1.000
10:34331176:G:T	A928D	1.000
10:34331181:T:A	R926S	1.000
10:34331181:T:G	R926S	1.000
10:34331182:C:G	R926T	1.000
10:34331184:G:C	F925L	1.000
10:34331184:G:T	F925L	1.000
10:34331185:A:C	F925C	1.000
10:34331185:A:G	F925S	1.000
10:34331186:A:G	F925L	1.000
10:34331187:G:C	S924R	1.000
10:34331187:G:T	S924R	1.000
10:34331189:T:G	S924R	1.000
10:34331193:A:C	N922K	1.000
10:34331193:A:T	N922K	1.000
10:34331198:A:G	C921R	1.000
10:34331273:C:G	A896P	1.000
10:34331281:A:G	L893P	1.000
10:34331281:A:T	L893Q	1.000
10:34331283:A:C	S892R	1.000
10:34331283:A:T	S892R	1.000
10:34331285:T:G	S892R	1.000
10:34331290:A:G	L890S	1.000
10:34359175:A:T	V680D	1.000
10:34359181:A:G	L678P	1.000
10:34359229:A:G	L662P	1.000
10:34359284:C:G	A644P	1.000
10:34359289:A:G	L642P	1.000
10:34359289:A:T	L642Q	1.000
10:34359307:A:G	L636P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001974 (10:34495598 C>A), RS1000005784 (10:34535998 A>T), RS1000007087 (10:34702273 T>C), RS1000012050 (10:34690055 T>C), RS1000016293 (10:34624527 A>G), RS1000022486 (10:34241555 T>A,C), RS1000027913 (10:34159821 G>T), RS1000030614 (10:34391418 G>A,T), RS1000032581 (10:34310054 A>C), RS1000042116 (10:34147151 A>G), RS1000048701 (10:34408500 T>G), RS1000052746 (10:34272947 A>C), RS1000061494 (10:34354492 C>T), RS1000063339 (10:34579552 CTCTGTG>C), RS1000066018 (10:34294925 G>A)

Disease associations

OMIM: gene MIM:606745 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), neural tube defect (MONDO:0018075), primary ovarian failure (MONDO:0005387)

Orphanet (4): Familial prostate cancer (Orphanet:1331), Neural tube defect (Orphanet:3388), Spina bifida and other spinal dysraphisms (Orphanet:823), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000464_13	Acute lymphoblastic leukemia (childhood)	9.000000e-06
GCST000770_2	Emphysema-related traits	8.000000e-07
GCST001083_4	Major depressive disorder	3.000000e-06
GCST001119_1	Schizophrenia	6.000000e-06
GCST007159_6	Corneal astigmatism	2.000000e-06
GCST007431_11	Lung function (FEV1/FVC)	8.000000e-12
GCST007876_113	Estimated glomerular filtration rate	1.000000e-08
GCST008156_109	Hip circumference adjusted for BMI	2.000000e-06
GCST010241_381	Apolipoprotein A1 levels	6.000000e-10
GCST010242_171	HDL cholesterol levels	2.000000e-11
GCST010703_68	Brain morphology (MOSTest)	2.000000e-08
GCST010988_439	Adult body size	6.000000e-12
GCST011039_2	Parkinson’s disease progression (composite)	1.000000e-06
GCST90000025_398	Appendicular lean mass	6.000000e-11
GCST90000025_399	Appendicular lean mass	2.000000e-11
GCST90007007_6	Gut microbiota relative abundance (Sutterella)	3.000000e-06
GCST90013407_43	Liver enzyme levels (gamma-glutamyl transferase)	8.000000e-19

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:1002040	Corneal astigmatism
EFO:0004713	FEV/FVC ratio
EFO:0008039	BMI-adjusted hip circumference
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0008336	disease progression measurement
EFO:0004980	appendicular lean mass
EFO:0007874	gut microbiome measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, decreases expression	6
bisphenol A	increases expression, affects expression, affects methylation, affects cotreatment, increases methylation (+1 more)	5
Valproic Acid	affects expression, decreases expression, increases methylation	3
arsenite	affects binding, decreases reaction, increases methylation	2
Nickel	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	affects phosphorylation	1
dibenzo(a,l)pyrene	decreases expression	1
avobenzone	increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Amphotericin B	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Cyclophosphamide	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

16 cell lines: 16 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0556	T98G	Cancer cell line	Male
CVCL_1086	BHY	Cancer cell line	Male
CVCL_1180	DOK	Cancer cell line	Male
CVCL_1350	KYSE-270	Cancer cell line	Male
CVCL_1351	KYSE-30	Cancer cell line	Male
CVCL_2315	BICR 78	Cancer cell line	Male
CVCL_E0WW	Ubigene KYSE-30 CCHCR1 KO	Cancer cell line	Male
CVCL_E0WX	Ubigene KYSE-30 CYP26B1 KO	Cancer cell line	Male
CVCL_E0WY	Ubigene KYSE-30 DDAH2 KO	Cancer cell line	Male
CVCL_E0WZ	Ubigene KYSE-30 FASN KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer