PARD3

protein-coding

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

Gene summary

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. [provided by RefSeq, Oct 2011]

MANE transcript

NM_001184785.2

Inheritance

—

ClinVar variants

P:2U:208B:37

Top phenotype

PARD3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr10:34,109,560-34,815,325

External References & Databases

Ensembl (ENSG00000148498)

Transcript & Mutation Effects

hg38 • Region Span ~705.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PARD3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 177

PARD3-related disorderTotal: 33

not providedTotal: 16

Neural tube defectTotal: 6

Prostate cancerTotal: 3

Premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001184785.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	17 clinvar	4 clinvar	26
missense	2 clinvar		188 clinvar	11 clinvar	5 clinvar	206
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	2	0	208	28	9	247

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 179 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001184785.2	RefSeq	NP_001171714.1	25	MANE Select
ENST00000374788.8	Ensembl	ENSP00000363920.3	25	MANE Select
NM_001184786.2	RefSeq	NP_001171715.1	24	Standard
NM_001184787.2	RefSeq	NP_001171716.1	24	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pard3ab	Danio rerio	Structure: retinal ganglion cell Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

pard3ab

Danio rerio

Structure: retinal ganglion cell

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

microtubule cytoskeleton organization
protein targeting to membrane
cell cycle
cell adhesion
establishment or maintenance of cell polarity

Molecular Function

protein binding
phosphatidylinositol-4,5-bisphosphate binding
phosphatidylinositol-3,4,5-trisphosphate binding
protein phosphatase binding
phosphatidylinositol-3-phosphate binding

Cellular Component

cytoplasm
cytosol
cytoskeleton
plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374789
Coding exons: 25
Length: 705766
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	702	784	0.895	0.0000450	8933
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.298

Intolerance Scores

LoFtool: 0.683
RVIS EVS: -0.92
RVIS percentile EVS: 9.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.743

Gene Damage Prediction

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