PARD3

par-3 family cell polarity regulator, the group of PDZ domain containing|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 10:34109559-34815325

Links

ENSG00000148498 ∙ NCBI:56288 ∙ OMIM:606745 ∙ HGNC:16051 ∙ Uniprot:Q8TEW0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PARD3 gene.

• Inborn genetic diseases (45 variants)
• not provided (14 variants)
• Premature ovarian failure (1 variants)
• Neural tube defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARD3 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				4	2	6
missense			44	4	3	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1		1	2
Total	0	0	45	8	6

Variants in PARD3

This is a list of pathogenic ClinVar variants found in the PARD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-34111165-G-A		PARD3-related disorder	Benign (Jan 20, 2020)
10-34111188-C-G		not specified	Uncertain significance (Jun 16, 2023)
10-34111200-G-T		not specified	Uncertain significance (Aug 21, 2023)
10-34111221-G-A		not specified	Uncertain significance (Oct 05, 2021)
10-34111254-C-T		not specified	Uncertain significance (Feb 14, 2023)
10-34111327-C-G		not specified	Uncertain significance (Dec 14, 2023)
10-34111412-G-A		PARD3-related disorder	Likely benign (Feb 01, 2023)
10-34111438-C-T		not specified	Uncertain significance (Jun 29, 2022)
10-34111475-C-T		PARD3-related disorder	Benign/Likely benign (Dec 01, 2022)
10-34111495-C-T		Neural tube defect	risk factor (May 01, 2016)
10-34111506-G-T		not specified	Uncertain significance (Oct 10, 2023)
10-34111532-G-A		PARD3-related disorder	Likely benign (Aug 28, 2019)
10-34111539-G-A		not specified	Uncertain significance (Sep 27, 2021)
10-34119614-G-A		not specified	Uncertain significance (Oct 29, 2021)
10-34119632-G-C		not specified	Uncertain significance (Aug 12, 2021)
10-34119670-C-T		not specified	Uncertain significance (May 13, 2022)
10-34119695-C-T		not specified	Uncertain significance (Dec 14, 2023)
10-34119708-T-C		PARD3-related disorder	Benign (Oct 21, 2019)
10-34119721-G-A		PARD3-related disorder	Benign (Jun 06, 2019)
10-34119727-G-A		not specified	Uncertain significance (Nov 01, 2022)
10-34119738-C-T		PARD3-related disorder	Likely benign (Sep 05, 2019)
10-34131466-G-C		PARD3-related disorder	Likely benign (Aug 09, 2019)
10-34269649-G-A		PARD3-related disorder	Likely benign (Aug 09, 2019)
10-34269684-C-T		not specified	Uncertain significance (Dec 19, 2022)
10-34269721-T-C		not specified	Uncertain significance (Dec 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PARD3	protein_coding	protein_coding	ENST00000374789	25	705766

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.956	0.0442	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	702	784	0.895	0.0000450	8933
Missense in Polyphen		260	328.82	0.79071		3648
Synonymous	0.322	279	286	0.976	0.0000169	2588
Loss of Function	6.30	14	71.5	0.196	0.00000434	762

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000593	0.000582
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.0000551	0.0000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000179	0.000176
Middle Eastern	0.0000551	0.0000544
South Asian	0.000101	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:27925688, PubMed:10954424). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688). {ECO:0000250|UniProtKB:Q99NH2, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:27925688}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:27925688}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Adherens junction - Homo sapiens (human);Endocytosis - Homo sapiens (human);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Chemokine signaling pathway;Signal Transduction;TCR;EGFR1;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Cell-Cell communication;TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• loftool: 0.683
• rvis_EVS: -0.92
• rvis_percentile_EVS: 9.81

Haploinsufficiency Scores

• pHI: 0.511
• hipred: Y
• hipred_score: 0.652
• ghis: 0.545

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.743

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pard3
• Phenotype: embryo 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; limbs/digits/tail 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); immune system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: pard3ab
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: microtubule cytoskeleton organization;protein targeting to membrane;cell cycle;cell adhesion;establishment or maintenance of cell polarity;transforming growth factor beta receptor signaling pathway;protein kinase C-activating G protein-coupled receptor signaling pathway;axonogenesis;protein localization;asymmetric cell division;negative regulation of peptidyl-threonine phosphorylation;myelination in peripheral nervous system;establishment of cell polarity;positive regulation of myelination;establishment or maintenance of epithelial cell apical/basal polarity;establishment of centrosome localization;regulation of cellular localization;protein-containing complex assembly;bicellular tight junction assembly;establishment of epithelial cell polarity
• Cellular component: cytoplasm;cytosol;cytoskeleton;plasma membrane;cell-cell junction;adherens junction;cell-cell adherens junction;bicellular tight junction;cell cortex;endomembrane system;apical plasma membrane;cell junction;protein-containing complex;internode region of axon;neuronal cell body;apical junction complex;axonal growth cone
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;protein phosphatase binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol binding;identical protein binding