PARD6G

Summary

PARD6G (par-6 family cell polarity regulator gamma, HGNC:16076) is a protein-coding gene on chromosome 18q23, encoding Partitioning defective 6 homolog gamma (Q9BYG4). Adapter protein involved in asymmetrical cell division and cell polarization processes.

Predicted to be involved in centrosome cycle; establishment or maintenance of epithelial cell apical/basal polarity; and regulation of cellular localization. Predicted to be located in cytosol; plasma membrane; and tight junction. Predicted to be part of PAR polarity complex. Predicted to be active in apical plasma membrane; cell cortex; and nucleus.

Source: NCBI Gene 84552 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_032510

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16076
Approved symbol	PARD6G
Name	par-6 family cell polarity regulator gamma
Location	18q23
Locus type	gene with protein product
Status	Approved
Aliases	PAR-6G, PAR6gamma
Ensembl gene	ENSG00000178184
Ensembl biotype	protein_coding
OMIM	608976
Entrez	84552

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000353265, ENST00000463384, ENST00000470488

RefSeq mRNA: 1 — MANE Select: NM_032510 NM_032510

CCDS: CCDS12022

Canonical transcript exons

ENST00000353265 — 3 exons

Exon	Start	End
ENSE00001273029	80202710	80202932
ENSE00001406309	80157232	80160606
ENSE00001941099	80247277	80247514

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2673 / max 108.5633, expressed in 1363 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172674	6.2673	1363

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	98.75	gold quality
secondary oocyte	CL:0000655	96.84	gold quality
upper leg skin	UBERON:0004262	95.53	gold quality
penis	UBERON:0000989	94.60	gold quality
skin of hip	UBERON:0001554	94.22	gold quality
oocyte	CL:0000023	94.02	gold quality
mammalian vulva	UBERON:0000997	91.47	gold quality
tibia	UBERON:0000979	91.21	gold quality
gingiva	UBERON:0001828	91.13	gold quality
gingival epithelium	UBERON:0001949	90.76	gold quality
pancreatic ductal cell	CL:0002079	90.05	silver quality
epithelial cell of pancreas	CL:0000083	89.04	silver quality
zone of skin	UBERON:0000014	89.03	gold quality
oral cavity	UBERON:0000167	88.76	gold quality
esophagus squamous epithelium	UBERON:0006920	88.74	gold quality
skin of leg	UBERON:0001511	88.47	gold quality
skin of abdomen	UBERON:0001416	88.45	gold quality
nipple	UBERON:0002030	87.68	gold quality
lower esophagus mucosa	UBERON:0035834	87.29	gold quality
epithelium of mammary gland	UBERON:0003244	85.95	gold quality
mammary duct	UBERON:0001765	85.91	gold quality
right uterine tube	UBERON:0001302	85.08	gold quality
right lobe of thyroid gland	UBERON:0001119	85.03	gold quality
thyroid gland	UBERON:0002046	85.03	gold quality
left lobe of thyroid gland	UBERON:0001120	85.01	gold quality
esophagus mucosa	UBERON:0002469	84.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.35	gold quality
tibialis anterior	UBERON:0001385	82.85	silver quality
seminal vesicle	UBERON:0000998	82.35	gold quality
vagina	UBERON:0000996	82.33	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	9.96
E-ANND-3	yes	5.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PARD6G, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
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-6778-3P	99.96	67.29	2693
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-5680	99.91	69.83	3421

Literature-anchored findings (GeneRIF, showing 2)

• this study is the first to identify Par6gamma as a component of the mother centriole and to report a role of a mother centriole protein in the regulation of centrosomal protein composition. (PMID:23264737)
• This paper shows Par6G as a negative regulator of the phosphatidylinositol 3’-kinase/phosphoinositide-dependent protein kinase 1/Akt pathway and epithelial cell proliferation and evidence for frequent inactivation of Par6G gene in epithelial cancers. (PMID:26073086)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pard6gb	ENSDARG00000036090
mus_musculus	Pard6g	ENSMUSG00000056214
rattus_norvegicus	Pard6g	ENSRNOG00000055157
drosophila_melanogaster	par-6	FBGN0026192
caenorhabditis_elegans	par-6	WBGENE00003921

Paralogs (2): PARD6A (ENSG00000102981), PARD6B (ENSG00000124171)

Protein

Protein identifiers

Partitioning defective 6 homolog gamma — Q9BYG4 (reviewed: Q9BYG4)

Alternative names: PAR6D

All UniProt accessions (2): Q9BYG4, K7ELH1

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins.

Subunit / interactions. Interacts with PARD3. Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1. Interacts with the N-terminal part of PRKCI and PRKCZ.

Subcellular location. Cytoplasm. Cell membrane. Cell junction. Tight junction.

Tissue specificity. Widely expressed, with a higher expression in fetal and adult kidney.

Domain organisation. The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases.

Similarity. Belongs to the PAR6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYG4-1	1	yes
Q9BYG4-2	2

RefSeq proteins (1): NP_115899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000270	PB1_dom	Domain
IPR001478	PDZ	Domain
IPR034868	PB1_Par6	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR051741	PAR6_homolog	Family
IPR053793	PB1-like	Domain

Pfam: PF00564, PF00595

UniProt features (9 total): domain 3, region of interest 2, splice variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYG4-F1	70.72	0.44

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 160 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, KEGG_TIGHT_JUNCTION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOCC_APICAL_PLASMA_MEMBRANE, KEGG_ENDOCYTOSIS, GOCC_CELL_CELL_JUNCTION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_BIPOLAR_CELL_POLARITY, HAMAI_APOPTOSIS_VIA_TRAIL_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, SENESE_HDAC3_TARGETS_DN, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX, GOCC_APICAL_PART_OF_CELL, GOCC_PROTEIN_KINASE_COMPLEX, GOBP_CELL_DIVISION

GO Biological Process (5): centrosome cycle (GO:0007098), establishment or maintenance of cell polarity (GO:0007163), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), cell division (GO:0051301), regulation of cellular localization (GO:0060341)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell cortex (GO:0005938), apical plasma membrane (GO:0016324), 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-1 pathways:

Category	Pathways
Cell-cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
cytoplasm	2
cell periphery	2
cell cycle process	1
microtubule organizing center organization	1
establishment or maintenance of apical/basal cell polarity	1
regulation of localization	1
regulation of cellular process	1
cellular localization	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane region	1
cell-cell junction	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARD6G	CDC42	P21181	944
PARD6G	PARD3	Q8TEW0	892
PARD6G	PRKCZ	Q05513	883
PARD6G	SMURF1	Q9HCE7	563
PARD6G	TJP1	Q07157	549
PARD6G	RAC1	P15154	529
PARD6G	TIAM1	Q13009	525
PARD6G	ANXA2	P07355	505
PARD6G	PRKCI	P41743	500
PARD6G	LLGL2	Q6P1M3	473
PARD6G	ADNP2	Q6IQ32	460
PARD6G	PARD3B	Q8TEW8	452
PARD6G	DLG2	Q15700	450
PARD6G	CLDN1	O95832	440
PARD6G	RHOA	P06749	427

IntAct

69 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
PARD6G	PRKCZ	psi-mi:“MI:0915”(physical association)	0.890
PRKCZ	NIPSNAP2	psi-mi:“MI:0914”(association)	0.730
PARD6G	PRKCI	psi-mi:“MI:0914”(association)	0.720
PARD6G	PRKCI	psi-mi:“MI:0915”(physical association)	0.720
PRKCI	PARD6G	psi-mi:“MI:0915”(physical association)	0.720
CDC42	PARD6G	psi-mi:“MI:0915”(physical association)	0.680
LLGL1	DNAJA2	psi-mi:“MI:0914”(association)	0.640
PRKCI	NIPSNAP2	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RAC1	PARD6G	psi-mi:“MI:0915”(physical association)	0.510
PARD3	PARD6G	psi-mi:“MI:0915”(physical association)	0.500
PARD6G	YWHAH	psi-mi:“MI:0915”(physical association)	0.500
MARK2	PARD6G	psi-mi:“MI:0915”(physical association)	0.500
ABCC4	PARD6G	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	PARD6G	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	PARD6G	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	PARD6G	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	PARD6G	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (59): PARD6G (Affinity Capture-MS), PARD6G (Affinity Capture-MS), PARD6G (Affinity Capture-MS), PARD6G (Affinity Capture-MS), PARD6G (Affinity Capture-MS), PARD6G (Two-hybrid), RBM14 (Two-hybrid), DMRTB1 (Two-hybrid), PRKCI (Two-hybrid), AKAP9 (Two-hybrid), PARD6G (Two-hybrid), PARD6G (Two-hybrid), PARD6G (Two-hybrid), RNF146 (Affinity Capture-Western), PARD6G (Affinity Capture-Luminescence)

ESM2 similar proteins: A2A699, A2AB59, A2AJA9, A5PKW4, A6NK89, A8MVW0, D3ZG83, F1MUS9, O09039, O14492, O14511, O15534, O35569, O35615, O70220, O94983, P46062, P56974, P70447, P98077, Q02779, Q09019, Q3U0S6, Q53LP3, Q5TCX8, Q5U651, Q63244, Q66L42, Q66L44, Q69ZH9, Q6ZUM4, Q80XF7, Q80Y50, Q8BGW3, Q8BL43, Q8BQU6, Q8JZP9, Q8N350, Q92886, Q96FS4

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, A5PKA5, F1MCA7, G5ECY0, O14907, O14910, O35274, O35867, O55164, O61967, O62674, O62675, O62676, O88951, O88952, P31016, P57105, P70175, P70587, P78352, P97879, Q0P5E6, Q0P5F3, Q12959, Q13424, Q13425, Q13884, Q14160, Q15599, Q22638, Q28626, Q28C55, Q2KIB6, Q32LE7, Q32LM6, Q3T0C9, Q3UHD6, Q4H4B6, Q5EBL8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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.

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	83.0×	4e-10
establishment of cell polarity	8	62.5×	2e-10
microtubule cytoskeleton organization	5	12.4×	5e-03
intracellular signal transduction	7	5.5×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1114 predictions. Top by Δscore:

Variant	Effect	Δscore
18:80202929:CAAA:C	acceptor_gain	1.0000
18:80202938:A:AC	acceptor_gain	1.0000
18:80247271:GCTTA:G	donor_loss	1.0000
18:80247272:CTTA:C	donor_loss	1.0000
18:80247273:TTAC:T	donor_loss	1.0000
18:80247274:TACCT:T	donor_loss	1.0000
18:80247275:ACCT:A	donor_loss	1.0000
18:80247276:C:G	donor_loss	1.0000
18:80247276:CCTTG:C	donor_gain	1.0000
18:80178833:T:TA	donor_gain	0.9900
18:80202695:CA:C	donor_gain	0.9900
18:80202696:AA:A	donor_gain	0.9900
18:80202704:CAGTA:C	donor_loss	0.9900
18:80202705:AGTAC:A	donor_loss	0.9900
18:80202706:GTA:G	donor_loss	0.9900
18:80202707:TACC:T	donor_loss	0.9900
18:80202708:A:C	donor_loss	0.9900
18:80202710:C:G	donor_loss	0.9900
18:80202757:G:GA	donor_gain	0.9900
18:80202928:CCAAA:C	acceptor_gain	0.9900
18:80202929:CAAAC:C	acceptor_gain	0.9900
18:80202930:AAA:A	acceptor_gain	0.9900
18:80202931:AA:A	acceptor_gain	0.9900
18:80202932:AC:A	acceptor_loss	0.9900
18:80202933:C:CC	acceptor_gain	0.9900
18:80202933:CTACA:C	acceptor_loss	0.9900
18:80202934:T:C	acceptor_loss	0.9900
18:80202936:CAA:C	acceptor_gain	0.9900
18:80202938:A:C	acceptor_gain	0.9900
18:80202942:A:T	acceptor_gain	0.9900

AlphaMissense

2432 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:80160162:A:T	V247D	1.000
18:80160242:G:C	N220K	1.000
18:80160242:G:T	N220K	1.000
18:80160261:T:A	D214V	1.000
18:80160261:T:C	D214G	1.000
18:80160318:A:T	I195N	1.000
18:80160381:A:T	I174N	1.000
18:80160387:A:G	F172S	1.000
18:80202784:A:T	I74N	1.000
18:80202910:A:G	F32S	1.000
18:80202913:C:A	R31M	1.000
18:80247283:C:A	K22N	1.000
18:80247283:C:G	K22N	1.000
18:80160168:A:T	V245D	0.999
18:80160174:A:G	L243P	0.999
18:80160174:A:T	L243H	0.999
18:80160195:A:C	M236R	0.999
18:80160195:A:G	M236T	0.999
18:80160195:A:T	M236K	0.999
18:80160243:T:A	N220I	0.999
18:80160255:A:T	V216D	0.999
18:80160261:T:G	D214A	0.999
18:80160262:C:A	D214Y	0.999
18:80160262:C:G	D214H	0.999
18:80160273:A:T	L210Q	0.999
18:80160276:A:G	L209P	0.999
18:80160316:A:G	S196P	0.999
18:80160318:A:C	I195S	0.999
18:80160318:A:G	I195T	0.999
18:80160320:G:C	F194L	0.999

dbSNP variants (sampled 300 via entrez): RS1000002882 (18:80203786 G>A), RS1000008403 (18:80215110 T>C), RS1000117690 (18:80236614 G>A,T), RS1000173819 (18:80220509 T>C), RS1000217718 (18:80239459 CA>C,CAA), RS1000222386 (18:80223848 A>C), RS1000346068 (18:80234177 C>G), RS1000353914 (18:80187263 G>A), RS1000356027 (18:80225515 T>C), RS1000367828 (18:80202781 T>C), RS1000407488 (18:80228079 G>A), RS1000419181 (18:80195024 C>G), RS1000443148 (18:80214756 G>C), RS1000505580 (18:80168619 A>G), RS1000525495 (18:80158700 T>C)

Disease associations

OMIM: gene MIM:608976 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	3
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Phthalic Acids	increases methylation	1
Zinc	increases expression, affects cotreatment	1
Lactic Acid	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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