PDZK1

Summary

PDZK1 (PDZ domain containing 1, HGNC:8821) is a protein-coding gene on chromosome 1q21.1, encoding Na(+)/H(+) exchange regulatory cofactor NHE-RF3 (Q5T2W1). A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. It is a selective cancer dependency (DepMap: 12.2% of cell lines).

This gene encodes a PDZ domain-containing scaffolding protein. PDZ domain-containing molecules bind to and mediate the subcellular localization of target proteins. The encoded protein mediates the localization of cell surface proteins and plays a critical role in cholesterol metabolism by regulating the HDL receptor, scavenger receptor class B type 1. Single nucleotide polymorphisms in this gene may be associated with metabolic syndrome, and overexpression of this gene may play a role in drug resistance of multiple myeloma. Pseudogenes of this gene are located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5174 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 50 total
• Cancer dependency (DepMap): dependent in 12.2% of screened cell lines
• MANE Select transcript: NM_001201325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8821
Approved symbol	PDZK1
Name	PDZ domain containing 1
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PDZD1, NHERF3, CAP70, CLAMP, NaPi-Cap1
Ensembl gene	ENSG00000174827
Ensembl biotype	protein_coding
OMIM	603831
Entrez	5174

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000344770, ENST00000417171, ENST00000429537, ENST00000443667, ENST00000451928, ENST00000465595, ENST00000466386, ENST00000907408, ENST00000907409, ENST00000907410, ENST00000907411, ENST00000907412, ENST00000907413, ENST00000907414, ENST00000907415, ENST00000907416, ENST00000907417, ENST00000907418, ENST00000907419, ENST00000907420, ENST00000960532, ENST00000960533, ENST00000960534, ENST00000960535

RefSeq mRNA: 5 — MANE Select: NM_001201325 NM_001201325, NM_001201326, NM_001371359, NM_001371361, NM_002614

CCDS: CCDS72859, CCDS72860

Canonical transcript exons

ENST00000417171 — 9 exons

Exon	Start	End
ENSE00001365469	145670985	145671489
ENSE00001372163	145687812	145688023
ENSE00001710717	145682500	145682636
ENSE00001759427	145686477	145686726
ENSE00001784849	145673657	145673881
ENSE00001787521	145678449	145678645
ENSE00003660712	145672730	145673020
ENSE00003787489	145680912	145681107
ENSE00003897394	145707317	145707368

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.82.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2582 / max 376.0785, expressed in 257 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14117	1.2789	113
14118	0.3350	62
14125	0.1628	98
14122	0.1552	48
14127	0.0903	37
14126	0.0720	26
14123	0.0524	23
14119	0.0443	23
14124	0.0325	18
14121	0.0179	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	98.82	gold quality
metanephros cortex	UBERON:0010533	97.63	gold quality
kidney	UBERON:0002113	97.08	gold quality
duodenum	UBERON:0002114	96.89	gold quality
right lobe of liver	UBERON:0001114	96.39	gold quality
liver	UBERON:0002107	96.25	gold quality
cortex of kidney	UBERON:0001225	92.87	gold quality
cerebellar cortex	UBERON:0002129	90.40	gold quality
cerebellum	UBERON:0002037	90.33	gold quality
cerebellar hemisphere	UBERON:0002245	90.32	gold quality
gall bladder	UBERON:0002110	89.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.40	gold quality
small intestine	UBERON:0002108	88.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.21	gold quality
body of pancreas	UBERON:0001150	85.06	gold quality
islet of Langerhans	UBERON:0000006	84.98	gold quality
pancreas	UBERON:0001264	84.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.77	gold quality
rectum	UBERON:0001052	78.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.92	gold quality
mucosa of transverse colon	UBERON:0004991	71.86	gold quality
intestine	UBERON:0000160	71.65	gold quality
left adrenal gland cortex	UBERON:0035825	71.61	gold quality
adrenal tissue	UBERON:0018303	71.30	gold quality
left adrenal gland	UBERON:0001234	71.17	gold quality
right adrenal gland cortex	UBERON:0035827	71.17	gold quality
right adrenal gland	UBERON:0001233	71.06	gold quality
calcaneal tendon	UBERON:0003701	71.03	gold quality
adrenal gland	UBERON:0002369	70.75	gold quality
endometrium	UBERON:0001295	69.55	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	522.63
E-GEOD-114530	yes	485.33
E-HCAD-10	yes	378.12
E-CURD-119	yes	45.02
E-MTAB-9388	yes	11.37
E-ANND-3	yes	10.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA

miRNA regulators (miRDB)

40 targeting PDZK1, 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-520G-5P	99.99	66.76	658
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-7852-3P	98.37	67.98	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of PDZK1 is associated with a drug-resistance phenotype in multiple myeloma. (PMID:15215163)
• PDZK1 plays a role in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules. (PMID:15304510)
• We have examined the ability of Bcr to interact with other epithelial PDZ proteins and found specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3 (PMID:15494376)
• Double transfection of OCTN2 with PDZK1 intestinal and kidney-enriched PDZ protein))stimulated the uptake by OCTN2 of its endogenous substrate carnitine. (PMID:15523054)
• oligomerization of Oatp1a1 with PDZK1 is critical for its proper subcellular localization and function (PMID:15994332)
• intracellular sorting of the somatostatin receptor subtype 5 is regulated by interactions with PDZ domain proteins PIST/GOPC and PDZK1 (PMID:16012170)
• PEPT2-PDZK1 interaction thus plays a physiologically important role in both oligopeptide handling as well as peptide-like drug transport in the human kidney (PMID:16738539)
• The mechanisms by which the C-terminal four amino acids of inducible nitric oxide synthase (NOS2) interact with proteins that contain PDZ (PSD-95/DLG/ZO-1) domains resulting in the translocation of NOS2 to the cellular apical domain, is analyzed. (PMID:17507652)
• The interaction of PDZ proteins with hOAT4 may be cell-specific. In placenta, a different set of interacting proteins from PDZK1 and NHERF1 may be required to modulate hOAT4 activity. (PMID:17602283)
• Pdzk1 plays a specific role in stabilizing Muc17 in the apical membrane of small intestinal enterocytes. (PMID:17990980)
• Established a mouse model to study human reverse cholesterol transport by expressing CLA-1, human PDZK1, and human apoA-I gene. (PMID:18403724)
• Endogenous PPARalpha regulates PDZK1 expression. (PMID:18955051)
• While the presence of forskolin results in an increase in OCTN2 protein expression, the increase in uptake capacity may be compensated by the decreased expression of PDZK1, NHERF1 or NHERF2. (PMID:19091402)
• The tail of PDZK1 interacts with the PDZ domains of EBP50, and this interaction is negatively regulated by the intramolecular association of the tail of PDZK1 with its first PDZ domain. (PMID:19173579)
• findings suggest that PDZ domain containing 1 (PDZK1)_i33968C > T genetic variants may be associated with a higher risk of exhibiting metabolic syndrome (PMID:19321583)
• In HEK cells, which express little PDZK1, additional transfection of PDZK1 was required for UTP to inhibit DRA. (PMID:19447883)
• NHERF3 colocalizes and directly binds NHE3 at the plasma membrane under basal conditions. (PMID:19535329)
• Data show that PDZK1/EBP50/ezrin form a regulated ternary complex in vitro and in vivo. (PMID:20237154)
• The SR-BI partner PDZK1 facilitates hepatitis C virus entry. (PMID:20949066)
• Although PDZK1 binding is required for optimal cell surface expression of oatp1a1, phosphorylation provides a mechanism for fast regulation of the distribution of oatp1a1 between the cell surface and intracellular vesicular pools. (PMID:21183661)
• Human prostacyclin receptor interacts with the PDZ adapter protein PDZK1; this interaction plays important role in endothelial cell migration and angiogenesis. (PMID:21653824)
• PDZ domain-containing 1 (PDZK1) protein regulates phospholipase C-beta3 (PLC-beta3)-specific activation of somatostatin by forming a ternary complex with PLC-beta3 and somatostatin receptors. (PMID:22528496)
• Upregulation of PDZK1 could have an important role in the development of melasma in connection with estrogen through NHE, CFTR, and SLC26A3. (PMID:22696060)
• Antibody screening revealed 3 candidate prognostic markers in breast cancer: the Anillin (ANLN); PDZ-Binding Kinase (PBK); and, PDZ-Domain Containing 1 (PDZK1). (PMID:23547718)
• These results clarify the relationship between ER-alpha and PDZK1, propose a direct relationship between PDZK1 and IGF1R, and identify a novel oncogenic activity for PDZK1 in breast cancer. (PMID:23821363)
• NHERF3 is a key regulator of organic transport in the kidney, particularly MRP4-mediated clearance of drug molecules. (PMID:24436471)
• PDZK1 and NHERF1 regulate the transport function of OATP1A2 by modulating protein internalization via a clathrin-dependent pathway and by enhancing protein stability. (PMID:24728453)
• Correlation between PDZK1, Cdc37, Akt and breast cancer malignancy: the role of PDZK1 in cell growth through Akt stabilization by increasing and interacting with Cdc37 (PMID:24869908)
• Inflammation-induced loss of PDZK1 expression may contribute to the NHE3 dysfunction observed in the inflamed intestine. (PMID:25271043)
• Described is a structure of D-AKAP2 in complex with two interacting partners and the exact mechanism by which a segment that on its own is disordered presents an alpha-helix to PKA and a beta-strand to PDZK1. (PMID:25348485)
• PDZKA1 adaptor protein gene of urate transporters, is not associated with gout. (PMID:25362723)
• IRF3 activation by innate antiviral signaling represses TGF-beta-induced growth inhibition, gene regulation and epithelial-mesenchymal transition, and the generation of Treg effector lymphocytes from naive CD4(+) lymphocytes. (PMID:25526531)
• PDZK1, negatively regulates 5-HT2AR endocytosis and has no effect upon 5-HT2AR-mediated ERK1/2 phosphorylation. (PMID:25562428)
• PARP regulates estradiol-mediated cell growth by controlling the ER/IGF-1R/PDZK1 axis. (PMID:26183824)
• a PDZK1 single nucleotide polymorphism rs12129861 was found to be significantly associated with gout susceptibility (meta-analysis) (PMID:27720648)
• PDZK1 was defined as an independent prognostic factor for both OS and DFS. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC. (PMID:27993630)
• These findings have provided first lines of evidences that PDZK1 expression is negatively correlated with SHP-1 activation and poor clinical outcomes in clear cell renal cell carcinoma (ccRCC) . PDZK1 was identified as a novel tumor suppressor in ccRCC by negating SHP-1 activity (PMID:28692056)
• HNF1alpha, which has previously been described as a modulator of several transporters of the renal transportosome, is also a key determinant of PDZK1 transcription. (PMID:28724612)
• transactivation of the PDZK1-promoter by triiodothyronine mediated by thyroid hormone receptors (THR) alpha and beta. (PMID:28928085)
• Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. (PMID:29405165)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdzk1	ENSDARG00000022261
mus_musculus	Pdzk1	ENSMUSG00000038298
rattus_norvegicus	Pdzk1	ENSRNOG00000000096
caenorhabditis_elegans		WBGENE00006438

Paralogs (3): NHERF2 (ENSG00000065054), NHERF1 (ENSG00000109062), NHERF4 (ENSG00000172367)

Protein

Protein identifiers

Na(+)/H(+) exchange regulatory cofactor NHE-RF3 — Q5T2W1 (reviewed: Q5T2W1)

Alternative names: CFTR-associated protein of 70 kDa, Na(+)/H(+) exchanger regulatory factor 3, Na/Pi cotransporter C-terminal-associated protein 1, PDZ domain-containing protein 1, Sodium-hydrogen exchanger regulatory factor 3

All UniProt accessions (2): Q5T2W1, A0A0C4DG67

UniProt curated annotations — full annotation on UniProt →

Function. A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with NHERF1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function.

Subunit / interactions. Interacts with PDZK1IP1 and ABCC2. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex with NHERF1. Interacts with AKAP2, BCR, CFTR, SLC22A12, SLC22A4, SLC22A5, NHERF2 and SLC17A1. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus). Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). Interacts (via PDZ domains 1 and 3) with SLC5A8 (via PDZ-binding motif); interaction increases nicotinate transport activity of SLC5A8.

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Expression is limited to epithelial cells. Expressed in the kidney (brush border of proximal tubule), pancreas, liver, and small intestine. Expressed at a lower level in the adrenal cortex, testis and stomach. Overexpressed in breast, renal and lung carcinomas.

Domain organisation. The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3. Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains. The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1. The PDZ 1 domain interacts with BCR. The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1.

Similarity. Belongs to the NHER family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T2W1-1	1	yes
Q5T2W1-2	2

RefSeq proteins (5): NP_001188254, NP_001188255, NP_001358288, NP_001358290, NP_002605 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR051067	NHER	Family

Pfam: PF00595

UniProt features (45 total): modified residue 13, strand 13, domain 4, helix 4, compositionally biased region 3, sequence conflict 2, turn 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9RXO	X-RAY DIFFRACTION	1.2
9RXN	X-RAY DIFFRACTION	1.36
9RXP	X-RAY DIFFRACTION	1.43
6EZI	X-RAY DIFFRACTION	1.5
9RXR	X-RAY DIFFRACTION	1.69
9RXS	X-RAY DIFFRACTION	2
4Q2P	X-RAY DIFFRACTION	2.05
2VSP	X-RAY DIFFRACTION	2.41
3TMH	X-RAY DIFFRACTION	3.8
2EEI	SOLUTION NMR
2EEJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T2W1-F1	78.50	0.43

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 (13): 108, 148, 192, 250, 334, 348, 451, 492, 508, 510, 511, 512, 514

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, ELVIDGE_HYPOXIA_DN, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, STOSSI_RESPONSE_TO_ESTRADIOL, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (6): regulation of monoatomic anion transport (GO:0044070), protein localization to plasma membrane (GO:0072659), positive regulation of protein targeting to membrane (GO:0090314), carnitine transmembrane transport (GO:1902603), positive regulation of protein localization to membrane (GO:1905477), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961)

GO Molecular Function (7): signaling receptor binding (GO:0005102), scavenger receptor binding (GO:0005124), PDZ domain binding (GO:0030165), protein-membrane adaptor activity (GO:0043495), protein-containing complex binding (GO:0044877), transporter activator activity (GO:0141109), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), brush border (GO:0005903), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), microvillus membrane (GO:0031528), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein localization to membrane	2
positive regulation of cellular process	2
binding	2
microvillus	2
apical part of cell	2
cell projection membrane	2
monoatomic anion transport	1
regulation of monoatomic ion transport	1
protein localization to cell periphery	1
protein targeting to membrane	1
regulation of protein targeting to membrane	1
positive regulation of establishment of protein localization	1
carnitine transport	1
transmembrane transport	1
positive regulation of protein localization	1
regulation of protein localization to membrane	1
xenobiotic export from cell	1
detoxification	1
export across plasma membrane	1
protein binding	1
signaling receptor binding	1
protein domain specific binding	1
protein-macromolecule adaptor activity	1
transporter activity	1
molecular function activator activity	1
transporter regulator activity	1
membrane	1
cell periphery	1
cluster of actin-based cell projections	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDZK1	SLC9A3	P48764	941
PDZK1	CFTR	P13569	920
PDZK1	PDZK1IP1	Q13113	919
PDZK1	SLC26A3	P40879	903
PDZK1	SLC22A12	Q96S37	892
PDZK1	SCARB1	Q8WTV0	880
PDZK1	SLC2A9	Q9NRM0	866
PDZK1	SLC26A6	Q9BXS9	850
PDZK1	SLC17A1	Q14916	845
PDZK1	EZR	P15311	826
PDZK1	KIRREL2	Q6UWL6	818
PDZK1	SLC22A11	Q9NSA0	816
PDZK1	NHERF1	O14745	808
PDZK1	KIRREL1	Q96J84	768
PDZK1	KIRREL3	Q8IZU9	765

IntAct

1350 interactions, top by confidence:

A	B	Type	Score
PDZK1	ACE2	psi-mi:“MI:0915”(physical association)	0.790
ACE2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.790
PDZK1	CFTR	psi-mi:“MI:0915”(physical association)	0.780
CFTR	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.780
BCR	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.740
PDZK1	GFAP	psi-mi:“MI:0915”(physical association)	0.670
MED17	MED14	psi-mi:“MI:0914”(association)	0.640
PDZK1	SLC15A5	psi-mi:“MI:0407”(direct interaction)	0.620
PDZK1	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
PDZK1	SDK2	psi-mi:“MI:0407”(direct interaction)	0.620
SLC15A5	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.620
SDK2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.620
CYSLTR2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.620
E6	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.610
PDZK1	E6	psi-mi:“MI:0407”(direct interaction)	0.610
PDZK1	E6	psi-mi:“MI:0915”(physical association)	0.610
Tax	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.610
PDZK1	Tax	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (128): PEX5 (Two-hybrid), PDZK1 (Two-hybrid), SLC34A1 (Two-hybrid), SLC34A1 (Reconstituted Complex), SLC9A3 (Two-hybrid), SLC17A1 (Two-hybrid), ABCC2 (Two-hybrid), PDZK1 (Reconstituted Complex), ABCC2 (Co-localization), ARHGAP17 (Affinity Capture-MS), ASNSD1 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), BCR (Affinity Capture-MS), FRYL (Affinity Capture-MS), SHKBP1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5G4, A2ALK8, A8MUH7, A9CB74, F1M386, F1MSG6, F1PBJ0, O14745, O14907, O14936, O70589, P19878, P26045, P70290, P70441, P70600, Q00013, Q09506, Q14289, Q17QN6, Q28619, Q3SZK8, Q3T0X8, Q4L1J4, Q4R6G4, Q570Y9, Q5F488, Q5RCF7, Q5RDW4, Q5T2W1, Q5TCQ9, Q5ZIJ9, Q5ZJ00, Q60629, Q62915, Q69ZS7, Q6RHR9, Q865P3, Q8CHG7, Q8TB45

Diamond homologs: A0A1D5P556, A0A8C0TYJ0, A4D2P6, A5PKA5, A8MUH7, B7WN72, G5ECY0, O08774, O14745, O14924, O15085, O60879, P31007, P31016, P70175, P70441, P78352, P97879, Q09506, Q0D5P3, Q0QWG9, Q12959, Q13425, Q15599, Q15700, Q28619, Q28C55, Q3T0X8, Q3UHD6, Q4R6G4, Q5PYH5, Q5PYH6, Q5PYH7, Q5RCF7, Q5T2W1, Q5ZM14, Q61085, Q61235, Q62108, Q62696

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PKA	“up-regulates activity”	PDZK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC-mediated transmembrane transport	11	6.3×	3e-04
G alpha (q) signalling events	9	5.0×	8e-03
Transport of small molecules	17	4.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transport	13	15.7×	2e-09
chloride transmembrane transport	6	11.0×	2e-03
transport across blood-brain barrier	6	8.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1890 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145673020:A:AT	acceptor_loss	1.0000
1:145673021:CAGGT:C	acceptor_loss	1.0000
1:145673759:G:GT	donor_gain	1.0000
1:145673884:AAAAG:A	acceptor_gain	1.0000
1:145676155:G:GG	donor_gain	1.0000
1:145678445:T:TC	donor_loss	1.0000
1:145678447:GGTA:G	donor_loss	1.0000
1:145678448:TGGTA:T	donor_loss	1.0000
1:145678449:CTGG:C	donor_loss	1.0000
1:145678450:ACTGG:A	donor_loss	1.0000
1:145680911:AGG:A	donor_loss	1.0000
1:145680913:AAAG:A	donor_loss	1.0000
1:145680914:GAAAG:G	donor_gain	1.0000
1:145680957:G:GT	donor_gain	1.0000
1:145681106:G:A	acceptor_loss	1.0000
1:145681106:G:GA	acceptor_gain	1.0000
1:145681106:GGT:G	acceptor_gain	1.0000
1:145681107:A:AG	acceptor_gain	1.0000
1:145681108:CAGGT:C	acceptor_loss	1.0000
1:145681110:TACAG:T	acceptor_loss	1.0000
1:145681116:T:TA	acceptor_gain	1.0000
1:145682496:T:A	donor_loss	1.0000
1:145682499:AGGT:A	donor_loss	1.0000
1:145682512:G:GT	donor_gain	1.0000
1:145686473:T:A	donor_loss	1.0000
1:145686474:GTGAG:G	donor_loss	1.0000
1:145686475:GGTG:G	donor_loss	1.0000
1:145686477:AAGG:A	donor_loss	1.0000
1:145686478:CAAG:C	donor_loss	1.0000
1:145686725:GGTT:G	acceptor_gain	1.0000

AlphaMissense

3412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145678571:C:G	A290P	0.990
1:145687918:A:T	V35D	0.989
1:145687858:A:T	V55D	0.987
1:145678567:A:T	V291D	0.986
1:145686680:A:T	V86D	0.986
1:145687876:A:G	L49P	0.983
1:145687956:G:C	F22L	0.983
1:145687956:G:T	F22L	0.983
1:145687958:A:G	F22L	0.983
1:145680940:G:C	F255L	0.981
1:145680940:G:T	F255L	0.981
1:145680942:A:G	F255L	0.981
1:145686677:A:G	L87P	0.980
1:145687915:C:G	R36P	0.980
1:145686713:A:T	V75D	0.979
1:145687876:A:T	L49H	0.979
1:145678489:A:G	L317P	0.976
1:145680941:A:G	F255S	0.976
1:145672881:A:G	L452P	0.975
1:145687948:C:G	R25P	0.975
1:145687957:A:G	F22S	0.975
1:145686497:A:G	F147S	0.974
1:145686496:G:C	F147L	0.973
1:145686496:G:T	F147L	0.973
1:145686498:A:G	F147L	0.973
1:145678594:A:G	L282S	0.971
1:145687951:A:G	L24P	0.971
1:145687860:T:A	R54S	0.968
1:145687860:T:G	R54S	0.968
1:145673703:A:G	F390S	0.967

dbSNP variants (sampled 300 via entrez): RS1000424277 (1:145696920 G>A), RS1000727288 (1:145703114 A>C), RS1000759288 (1:145695241 C>T), RS1001109905 (1:145708081 C>A,T), RS1001190216 (1:145689151 G>A,T), RS1001201343 (1:145696494 G>A,T), RS1001650724 (1:145696126 C>T), RS1001766773 (1:145702639 A>C), RS1001824559 (1:145689492 G>A,T), RS1001941225 (1:145707329 G>A), RS1001944281 (1:145702376 G>A), RS1002000415 (1:145707643 T>C), RS1002091798 (1:145701135 G>A), RS1002808043 (1:145687610 A>C), RS1003545544 (1:145699200 T>C)

Disease associations

OMIM: gene MIM:603831 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000418_10	Uric acid levels	3.000000e-09
GCST000818_2	Urate levels	4.000000e-08
GCST001791_9	Urate levels	1.000000e-29
GCST002238_1	Contrast sensitivity	8.000000e-09
GCST002829_20	Urate levels in overweight individuals	2.000000e-06
GCST002829_36	Urate levels in overweight individuals	5.000000e-09
GCST007725_23	Serum uric acid levels	3.000000e-15
GCST008972_151	Urate levels	1.000000e-69
GCST010277_8	Gout	6.000000e-07
GCST010637_1	Urate levels	9.000000e-29
GCST012338_1	Gout	5.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004531	urate measurement
EFO:0005419	contrast sensitivity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12129861	PDZK1		0.00	0

CTD chemical–gene interactions

87 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment, decreases expression, decreases reaction, affects expression (+1 more)	16
Benzo(a)pyrene	decreases expression, increases methylation	5
sodium arsenite	decreases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	4
bisphenol A	affects expression, increases expression	3
Fulvestrant	decreases expression, decreases reaction, increases expression	3
Acetaminophen	decreases expression	3
Diethylstilbestrol	increases expression	3
tetrachlorodian	decreases reaction, increases expression	2
4-nonylphenol	increases expression	2
Coumestrol	increases expression, affects reaction, affects cotreatment	2
Estriol	increases expression	2
Estrone	increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Genistein	increases expression	2
Raloxifene Hydrochloride	decreases reaction, increases expression, decreases expression	2
dicrotophos	decreases expression	1
daidzein	increases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
fenofibric acid	affects binding, increases expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	increases expression, decreases reaction	1
afimoxifene	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1

Clinical trials (associated diseases)

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