PARD6A

protein-coding

par-6 family cell polarity regulator alpha, the group of PDZ domain containing

Gene summary

This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001037281.2

Inheritance

—

ClinVar variants

U:39B:4

Top phenotype

PARD6A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr16:67,660,946-67,662,774

External References & Databases

Ensembl (ENSG00000102981)

Transcript & Mutation Effects

hg38 • Region Span ~1.8 kb

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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 PARD6A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 38

PARD6A-related disorderTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001037281.2. 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				3 clinvar		3
missense			38 clinvar	1 clinvar		39
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	4	0	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001037281.2	RefSeq	NP_001032358.1	3	MANE Select
ENST00000458121.7	Ensembl	ENSP00000392388.1	3	MANE Select
NM_016948.3	RefSeq	NP_058644.1	3	Standard
ENST00000219255.3	Ensembl	ENSP00000219255.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Axon guidance - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Rap1 signaling pathway - Homo sapiens (human)

Biological Process

negative regulation of protein phosphorylation
centrosome cycle
establishment or maintenance of cell polarity
transforming growth factor beta receptor signaling pathway
viral process

Molecular Function

protein kinase C binding
protein binding
transcription factor binding
Rho GTPase binding
GTP-dependent protein binding

Cellular Component

ruffle
nucleus
centrosome
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219255
Coding exons: 3
Length: 1833
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125733
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.69	162	235	0.689	0.0000150	2199
Missense (PolyPhen)		51	80.593	0.63281		699
Synonymous	1.04	84	97.0	0.866	0.00000536	800
Loss of Function	1.54	5	10.3	0.483	7.87e-7	80

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000059	0.000046	rare
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in the formation of epithelial tight junctions. Association with PARD3 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 (PubMed:10873802). Regulates centrosome organization and function. Essential for the centrosomal recruitment of key proteins that control centrosomal microtubule organization (PubMed:20719959). {ECO:0000269|PubMed:10873802, ECO:0000269|PubMed:20719959}.;

Recessive Scores

pRec: 0.259

Intolerance Scores

LoFtool: 0.353
RVIS EVS: 0.04
RVIS percentile EVS: 56.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.651

Gene Damage Prediction

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