PARD6A

Summary

PARD6A (par-6 family cell polarity regulator alpha, HGNC:15943) is a protein-coding gene on chromosome 16q22.1, encoding Partitioning defective 6 homolog alpha (Q9NPB6). Adapter protein involved in asymmetrical cell division and cell polarization processes.

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.

Source: NCBI Gene 50855 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001037281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15943
Approved symbol	PARD6A
Name	par-6 family cell polarity regulator alpha
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PAR-6, PAR-6A, TAX40, PAR6alpha, TIP-40
Ensembl gene	ENSG00000102981
Ensembl biotype	protein_coding
OMIM	607484
Entrez	50855

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000219255, ENST00000458121, ENST00000602551, ENST00000602727, ENST00000858698, ENST00000858699, ENST00000858700, ENST00000858701, ENST00000858702, ENST00000913808, ENST00000954337, ENST00000954338

RefSeq mRNA: 2 — MANE Select: NM_001037281 NM_001037281, NM_016948

CCDS: CCDS10843, CCDS45514

Canonical transcript exons

ENST00000458121 — 3 exons

Exon	Start	End
ENSE00000690412	67661455	67661677
ENSE00001242881	67660960	67661101
ENSE00001665446	67661896	67662774

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 93.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5654 / max 72.4384, expressed in 917 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154674	2.0294	836
154673	0.3783	166
154675	0.1576	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.52	gold quality
cerebellar hemisphere	UBERON:0002245	92.94	gold quality
cerebellar cortex	UBERON:0002129	92.90	gold quality
cerebellum	UBERON:0002037	92.37	gold quality
prefrontal cortex	UBERON:0000451	91.00	gold quality
sperm	CL:0000019	90.54	gold quality
right frontal lobe	UBERON:0002810	90.19	gold quality
paraflocculus	UBERON:0005351	90.13	gold quality
right testis	UBERON:0004534	89.99	gold quality
gluteal muscle	UBERON:0002000	89.72	silver quality
frontal pole	UBERON:0002795	89.68	gold quality
left testis	UBERON:0004533	89.53	gold quality
male germ cell	CL:0000015	89.27	gold quality
triceps brachii	UBERON:0001509	89.27	silver quality
cingulate cortex	UBERON:0003027	89.19	gold quality
anterior cingulate cortex	UBERON:0009835	89.11	gold quality
adenohypophysis	UBERON:0002196	88.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.59	gold quality
frontal lobe	UBERON:0016525	88.14	gold quality
frontal cortex	UBERON:0001870	88.13	gold quality
putamen	UBERON:0001874	88.13	gold quality
pituitary gland	UBERON:0000007	88.12	gold quality
neocortex	UBERON:0001950	87.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.87	gold quality
nucleus accumbens	UBERON:0001882	87.43	gold quality
amygdala	UBERON:0001876	87.42	gold quality
body of pancreas	UBERON:0001150	87.31	gold quality
cerebellar vermis	UBERON:0004720	87.25	gold quality
testis	UBERON:0000473	86.98	gold quality
cerebral cortex	UBERON:0000956	86.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.51
E-GEOD-99795	no	26.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting PARD6A, 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-6752-3P	99.72	66.71	1587
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-3674	97.01	68.86	1171

Literature-anchored findings (GeneRIF, showing 34)

• Partitioning-defective protein 6 associated constitutively with endogenous aPKCs. (PMID:14976222)
• crystal structure of the complex of PKCiota and Par6alpha PB1 domains to a resolution of 1.5 A (PMID:15590654)
• A rare A/G polymorphism in the promoter of the Par6alpha gene is associated with reduced fasting glycaemia, increased glucose tolerance and reduced serum nonesterified fatty Acids concentrations. (PMID:15744531)
• 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)
• Studies in this review confirm that signaling by Par6alpha controls the migration of immature granule neurons down the Bergmann glial fibers into the internal granule cell layer in which they establish synaptic connections. (PMID:17050699)
• 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)
• Par6alpha-mediated inhibition of insulin-dependent glycogen synthesis in C2C12 cells depends on the direct interaction of Par6alpha with aPKC and on aPKC-mediated T34 phosphorylation of Akt1. (PMID:17335965)
• Par6 was characterized as a dual-location protein. (PMID:17420281)
• Shear stress-induced directed migratory polarity is modulated by exogenous growth factors and dependent on Par6 activity and shear stress direction in endothelial cells (PMID:17586613)
• In vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling. (PMID:17976838)
• Neph1-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity (PMID:18562307)
• in addition to regulating cell polarization processes, Par6 is an inducer of cell proliferation in breast epithelial cells. (PMID:18922891)
• Ect2 and PKCiota are genetically and functionally linked in NSCLC, acting to coordinately drive tumor cell proliferation and invasion through formation of an oncogenic PKCiota-Par6alpha-Ect2 complex. (PMID:19617897)
• the TGFbeta-Par6 polarity pathway has a role in breast cancer progression (PMID:19667198)
• Par6alpha controls centrosome organization through its association with the dynactin subunit p150(Glued). (PMID:20719959)
• Data show that DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. (PMID:21170030)
• Data indicate that both tumor focality and Par3/Par6/atypical protein kinase C (APKC) expression were significantly associated with tumor recurrence. (PMID:21549621)
• Pak6 is a binding partner and a outatuve effector protein for the atypical rho GTPase cdc42 homologous protein. (PMID:22339630)
• Atypical protein kinase C kinase activity, as well as an association with PAR6, were found to be important for PAR6 phosphorylation. (PMID:23249950)
• Par6 negatively regulates trophoblast fusion via its roles on tight junctions and cytoskeleton dynamics and provide novel insight into the contribution of this polarity marker in altered trophoblast cell fusion typical of preeclampsia. (PMID:23341197)
• Morg1 facilitates Par6-aPKC binding to Crb3 for definition of apical identity of epithelial cells. (PMID:23439680)
• BDNF can regulate formation of functional synapses by increasing the expression of the RhoA inhibitors, Par6C and Rnd3. (PMID:23762244)
• TGFbeta induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKCzeta. The p-Par6-aPKCzeta complex is important for cell migration and invasion. (PMID:25756394)
• Shp2 promotes metastasis of prostate cancer by attenuating the PAR3/PAR6/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition (PMID:26050620)
• 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)
• Roles of partitioning-defective protein 6 (Par6) and its complexes in the proliferation, migration and invasion of cancer cells (PMID:28590507)
• Studies indicate that the PAR3-PAR6-aPKC complex are important for the establishment of neuronal polarity [Review]. (PMID:29696344)
• In T84 cells, overexpression of Par-6 causes intestinal barrier dysfunction. Lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction and increase in Par-6 expression was prevented by AhR activation. (PMID:29992488)
• In Par6A knockout cells, we find that active Cdc42 is more mobile at the apical membrane compared to control cells and that wild type Cdc42 is more diffusely localized throughout the cell, indicating that Par6A is required to restrict Cdc42 signaling. (PMID:30408122)
• The pathological analysis confirmed the correlation between Par6 expression and the prognosis in human glioma tissues, suggesting the regulation of Par6 expression regulates glioma tumorigenesis and progression. (PMID:31914615)
• A polybasic domain in aPKC mediates Par6-dependent control of membrane targeting and kinase activity. (PMID:32580209)
• Partitioning defective 6 homolog alpha (PARD6A) promotes epithelial-mesenchymal transition via integrin beta1-ILK-SNAIL1 pathway in ovarian cancer. (PMID:35379775)
• Par6 Enhances Glioma Invasion by Activating MEK/ERK Pathway Through a LIN28/let-7d Positive Feedback Loop. (PMID:36542194)
• FOXN2, identified as a novel biomarker in serum, modulates the transforming growth factor-beta signaling pathway through its interaction with partitioning defective 6 homolog alpha, contributing to the pathogenesis of gastric cancer. (PMID:38954805)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pard6a	ENSDARG00000069378
mus_musculus	Pard6a	ENSMUSG00000005699
rattus_norvegicus	Pard6a	ENSRNOG00000017746
drosophila_melanogaster	par-6	FBGN0026192
caenorhabditis_elegans	par-6	WBGENE00003921

Paralogs (2): PARD6B (ENSG00000124171), PARD6G (ENSG00000178184)

Protein

Protein identifiers

Partitioning defective 6 homolog alpha — Q9NPB6 (reviewed: Q9NPB6)

Alternative names: PAR6C, Tax interaction protein 40

All UniProt accessions (2): Q9NPB6, R4GMM2

UniProt curated annotations — full annotation on UniProt →

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. Regulates centrosome organization and function. Essential for the centrosomal recruitment of key proteins that control centrosomal microtubule organization.

Subunit / interactions. Interacts with MAP2K5. Interacts with PARD3. Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1. Interacts with the N-terminal part of PRKCI and PRKCZ. Part of a complex with PARD3, CDC42 or RAC1 and PRKCI or PRKCZ. Part of a complex with LLGL1 and PRKCI. Interacts with human T-cell leukemia virus type I TAX protein. Interacts with PALS1 and CRB3. Interacts with TGFBR1; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with ECT2 (‘Thr-359’ phosphorylated form) and PRKCI. Interacts with DCTN1 and PCM1.

Subcellular location. Cytoplasm. Cell membrane. Cell projection. Ruffle. Cell junction. Tight junction. Cytoskeleton. Microtubule organizing center. Centrosome. Centriolar satellite.

Tissue specificity. Expressed in pancreas, skeletal muscle, brain and heart. Weakly expressed in kidney and placenta.

Post-translational modifications. Phosphorylated by the TGF-beta receptor. Ubiquitinated by the SCF(FBXO31) complex, leading to its proteasomal degradation.

Domain organisation. The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases. The PB1 domain mediates interactions with MAP2K5. The PDZ domain mediates the interaction with CRB3.

Similarity. Belongs to the PAR6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPB6-1	1	yes
Q9NPB6-2	2

RefSeq proteins (2): NP_001032358, NP_058644 (=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 (23 total): strand 6, domain 3, mutagenesis site 3, helix 3, region of interest 3, modified residue 2, chain 1, sequence variant 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WMH	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPB6-F1	74.20	0.47

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 (2): 278, 345

Mutagenesis-validated functional residues (3):

Position	Phenotype
19	loss of interaction with ect2 and prkci.
28	slight decrease of interaction with prkci. loss of interaction with prkci; when associated with a-89.
89	slight decrease of interaction with prkci. loss of interaction with prkci; when associated with a-28.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-420029	Tight junction interactions
R-HSA-4608870	Asymmetric localization of PCP proteins
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013424	RHOV GTPase cycle

MSigDB gene sets: 179 (showing top): ATF_B, RNGTGGGC_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, chr16q22, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELLULAR_COMPONENT_MAINTENANCE, KEGG_TIGHT_JUNCTION, TGACCTY_ERR1_Q2, GOCC_RUFFLE, GOMF_GTPASE_BINDING

GO Biological Process (9): centrosome cycle (GO:0007098), establishment or maintenance of cell polarity (GO:0007163), viral process (GO:0016032), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), cell-cell junction maintenance (GO:0045217), positive regulation of protein secretion (GO:0050714), cell division (GO:0051301), regulation of cellular localization (GO:0060341), positive regulation of protein localization to centrosome (GO:1904781)

GO Molecular Function (4): protein-macromolecule adaptor activity (GO:0030674), GTP-dependent protein binding (GO:0030742), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (16): ruffle (GO:0001726), nucleus (GO:0005634), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cell cortex (GO:0005938), apical plasma membrane (GO:0016324), centriolar satellite (GO:0034451), tight junction (GO:0070160), PAR polarity complex (GO:0120157), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	4
Signaling by TGF-beta Receptor Complex	1
Cell-cell junction organization	1
PCP/CE pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cellular process	2
protein binding	2
cytoplasm	2
cell periphery	2
cell cycle process	1
microtubule organizing center organization	1
biological_process	1
establishment or maintenance of apical/basal cell polarity	1
cell junction maintenance	1
cell-cell junction organization	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
regulation of localization	1
regulation of cellular process	1
cellular localization	1
protein localization to centrosome	1
positive regulation of protein localization	1
regulation of protein localization to centrosome	1
molecular adaptor activity	1
GTPase binding	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
membrane	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane region	1
centrosome	1
cell-cell junction	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARD6A	PARD3	Q8TEW0	991
PARD6A	PRKCZ	Q05513	940
PARD6A	CDC42	P21181	905
PARD6A	PATJ	Q8NI35	814
PARD6A	PRKCI	P41743	729
PARD6A	PALS1	Q8N3R9	728
PARD6A	NPHP4	O75161	682
PARD6A	TIAM1	Q13009	618
PARD6A	SCRIB	Q14160	584
PARD6A	SMURF1	Q9HCE7	567
PARD6A	CRB3	Q9BUF7	551
PARD6A	BCAR1	P56945	548
PARD6A	NPHP1	O15259	545
PARD6A	RAC1	P15154	544
PARD6A	CLDN1	O95832	526

IntAct

87 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PRKCI	PARD6A	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0407”(direct interaction)	0.950
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
PRKCZ	PARD6A	psi-mi:“MI:0915”(physical association)	0.910
PARD6A	PRKCZ	psi-mi:“MI:0403”(colocalization)	0.910
PARD6A	PRKCZ	psi-mi:“MI:0915”(physical association)	0.910
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0915”(physical association)	0.890
PARD6A	PARD3	psi-mi:“MI:0915”(physical association)	0.810
PARD3	PARD6A	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (119): PARD6A (Two-hybrid), RICTOR (Affinity Capture-Western), PARD6A (Affinity Capture-MS), PARD6A (Two-hybrid), PARD6A (Two-hybrid), PARD6A (Co-fractionation), PARD6A (Reconstituted Complex), PARD6A (Two-hybrid), PARD6A (Two-hybrid), GRB2 (Affinity Capture-Luminescence), PIK3R3 (Affinity Capture-Luminescence), TGFBR1 (Affinity Capture-Western), PARD6A (Affinity Capture-Western), PRKCI (Two-hybrid), EPHB4 (Affinity Capture-MS)

ESM2 similar proteins: A2A288, A2A699, A2AEV7, A2ARS0, A5PKW4, A6NIX2, A8MVW0, B2RXF5, C9JTQ0, D3ZG83, E1BKA3, F1MUS9, O09039, O14559, O43900, O75427, P98077, Q02779, Q16584, Q18PE0, Q1JQB5, Q2M3V2, Q3U0S6, Q53LP3, Q5BJT1, Q5U2Z2, Q5U651, Q66HA1, Q66L42, Q6NY19, Q6ZUM4, Q7TQJ8, Q80VL3, Q80VM4, Q80XI6, Q8BLS7, Q8NCA9, Q91XC0, Q96FS4, Q96HB5

Diamond homologs: A6QQZ7, A8E0R9, A8KBF6, A9CB74, B4F7E7, D3ZAA9, E2QY99, O88910, O88954, P15454, P31006, P44310, P46195, P49697, P57888, P93757, P97879, Q00013, Q0I5L8, Q12DV7, Q13368, Q135N9, Q14168, Q16774, Q17QN6, Q1AVZ3, Q1G9H8, Q1QSI1, Q21EC9, Q24210, Q2GD44, Q2KA85, Q2NQS9, Q2QPW1, Q2YD10, Q3AQL3, Q47UB3, Q48Q15, Q4K3R4, Q4L1J4

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
DVL2	up-regulates	PARD6A	binding
PARD6A	up-regulates	RAC1
TGFBR2	up-regulates	PARD6A	phosphorylation
PARD6A	“up-regulates activity”	PRKCA	binding
PARD6A	“form complex”	PARD6/SMURF1	binding
PRKCI	“up-regulates quantity by stabilization”	PARD6A	phosphorylation
PRKCZ	“up-regulates quantity by stabilization”	PARD6A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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	6	89.4×	2e-08
Wnt signaling pathway, planar cell polarity pathway	5	58.4×	5e-06
small GTPase-mediated signal transduction	5	23.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

445 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67661097:GCAAA:G	donor_gain	1.0000
16:67661102:G:GG	donor_gain	1.0000
16:67661673:GCGGG:G	donor_gain	1.0000
16:67661891:A:AG	acceptor_gain	1.0000
16:67661892:G:GG	acceptor_gain	1.0000
16:67661892:GCA:G	acceptor_gain	1.0000
16:67661100:AA:A	donor_gain	0.9900
16:67661445:C:CA	acceptor_gain	0.9900
16:67661453:A:AG	acceptor_gain	0.9900
16:67661453:AGTTT:A	acceptor_gain	0.9900
16:67661454:G:GG	acceptor_gain	0.9900
16:67661454:GTTT:G	acceptor_gain	0.9900
16:67661454:GTTTG:G	acceptor_gain	0.9900
16:67661675:GGG:G	donor_gain	0.9900
16:67661676:GG:G	donor_gain	0.9900
16:67661676:GGG:G	donor_gain	0.9900
16:67661677:GG:G	donor_gain	0.9900
16:67661678:GTG:G	donor_loss	0.9900
16:67661679:T:A	donor_loss	0.9900
16:67661680:GAG:G	donor_loss	0.9900
16:67661683:G:GT	donor_gain	0.9900
16:67661685:GGG:G	donor_gain	0.9900
16:67661686:GGG:G	donor_gain	0.9900
16:67661888:T:TA	acceptor_gain	0.9900
16:67661892:GC:G	acceptor_gain	0.9900
16:67661892:GCAGA:G	acceptor_gain	0.9900
16:67661101:AGT:A	donor_loss	0.9800
16:67661102:GTAAG:G	donor_loss	0.9800
16:67661440:A:AG	acceptor_gain	0.9800
16:67661449:TTCCA:T	acceptor_loss	0.9800

AlphaMissense

2213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67662118:T:C	F171S	1.000
16:67662124:T:A	I173N	1.000
16:67662187:T:A	I194N	1.000
16:67662244:A:T	D213V	1.000
16:67662250:T:C	I215T	1.000
16:67662262:A:T	N219I	1.000
16:67662263:T:A	N219K	1.000
16:67662263:T:G	N219K	1.000
16:67662021:T:C	F139L	0.999
16:67662023:C:A	F139L	0.999
16:67662023:C:G	F139L	0.999
16:67662114:G:C	G170R	0.999
16:67662124:T:C	I173T	0.999
16:67662124:T:G	I173S	0.999
16:67662183:T:C	F193L	0.999
16:67662185:C:A	F193L	0.999
16:67662185:C:G	F193L	0.999
16:67662187:T:C	I194T	0.999
16:67662187:T:G	I194S	0.999
16:67662214:C:A	A203D	0.999
16:67662229:T:C	L208P	0.999
16:67662232:T:A	L209Q	0.999
16:67662243:G:C	D213H	0.999
16:67662244:A:C	D213A	0.999
16:67662244:A:G	D213G	0.999
16:67662250:T:A	I215N	0.999
16:67662250:T:G	I215S	0.999
16:67662310:T:A	M235K	0.999
16:67662310:T:G	M235R	0.999
16:67662331:T:A	L242H	0.999

dbSNP variants (sampled 300 via entrez): RS1000930506 (16:67661455 T>C), RS1001091321 (16:67661814 G>A,T), RS1004858158 (16:67662569 C>T), RS1004936452 (16:67661314 C>A,T), RS1005124259 (16:67660589 C>A,G,T), RS1007705936 (16:67663009 C>A,T), RS1011064739 (16:67659581 G>A), RS1012127877 (16:67661678 G>A), RS1013547623 (16:67659887 G>A,C), RS1015529840 (16:67662035 CTCAG>C), RS1016169059 (16:67662279 G>A), RS1016963855 (16:67660992 C>T), RS1017750146 (16:67659251 T>A), RS1017802690 (16:67659530 C>A,T), RS1018665535 (16:67659199 G>A,T)

Disease associations

OMIM: gene MIM:607484 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_42	Obesity-related traits	4.000000e-06
GCST002539_84	Schizophrenia	2.000000e-08
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Cisplatin	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
prothioconazole	increases expression	1
(+)-JQ1 compound	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Cytarabine	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZZ	Abcam HeLa PARD6A KO	Cancer cell line	Female
CVCL_F1BW	MDCK/wtPar6	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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