PICK1

Summary

PICK1 (protein interacting with PRKCA 1, HGNC:9394) is a protein-coding gene on chromosome 22q13.1, encoding PRKCA-binding protein (Q9NRD5). Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence.

The protein encoded by this gene contains a PDZ domain, through which it interacts with protein kinase C, alpha (PRKCA). This protein may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins. It has been shown to interact with multiple glutamate receptor subtypes, monoamine plasma membrane transporters, as well as non-voltage gated sodium channels, and may target PRKCA to these membrane proteins and thus regulate their distribution and function. This protein has also been found to act as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner. Three transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 9463 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility due to globozoospermia (Supportive, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_012407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9394
Approved symbol	PICK1
Name	protein interacting with PRKCA 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ1039K5, MGC15204
Ensembl gene	ENSG00000100151
Ensembl biotype	protein_coding
OMIM	605926
Entrez	9463

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 19 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000356976, ENST00000404072, ENST00000424694, ENST00000426258, ENST00000432756, ENST00000435166, ENST00000437453, ENST00000445628, ENST00000466374, ENST00000468288, ENST00000469819, ENST00000472724, ENST00000476157, ENST00000484021, ENST00000494434, ENST00000883303, ENST00000883304, ENST00000883305, ENST00000883306, ENST00000883307, ENST00000883308, ENST00000920341, ENST00000951425, ENST00000951426, ENST00000951427, ENST00000951428, ENST00000951429, ENST00000951430

RefSeq mRNA: 3 — MANE Select: NM_012407 NM_001039583, NM_001039584, NM_012407

CCDS: CCDS13965

Canonical transcript exons

ENST00000356976 — 13 exons

Exon	Start	End
ENSE00000654149	38073773	38073823
ENSE00000654150	38074307	38074451
ENSE00001665209	38057404	38057587
ENSE00001902763	38074864	38075701
ENSE00003464998	38072477	38072610
ENSE00003533813	38070838	38070891
ENSE00003549872	38069033	38069122
ENSE00003563712	38065002	38065130
ENSE00003568732	38073000	38073092
ENSE00003572081	38067704	38067770
ENSE00003593180	38059234	38059345
ENSE00003619398	38057753	38057850
ENSE00003691009	38071682	38071744

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 95.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3054 / max 145.1865, expressed in 1780 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192235	13.0888	1753
192234	1.3140	581
192236	0.8866	393
192237	0.0161	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	95.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.46	gold quality
right uterine tube	UBERON:0001302	94.41	gold quality
left ovary	UBERON:0002119	94.06	gold quality
cerebellar hemisphere	UBERON:0002245	93.77	gold quality
pituitary gland	UBERON:0000007	93.68	gold quality
cerebellar cortex	UBERON:0002129	93.62	gold quality
right frontal lobe	UBERON:0002810	93.54	gold quality
left testis	UBERON:0004533	93.37	gold quality
right testis	UBERON:0004534	93.33	gold quality
mucosa of stomach	UBERON:0001199	93.27	gold quality
right ovary	UBERON:0002118	93.03	gold quality
body of pancreas	UBERON:0001150	92.93	gold quality
right lobe of thyroid gland	UBERON:0001119	92.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.78	gold quality
minor salivary gland	UBERON:0001830	92.66	gold quality
left lobe of thyroid gland	UBERON:0001120	92.55	gold quality
metanephros cortex	UBERON:0010533	92.37	gold quality
skin of abdomen	UBERON:0001416	92.24	gold quality
skin of leg	UBERON:0001511	92.18	gold quality
right lung	UBERON:0002167	91.98	gold quality
sural nerve	UBERON:0015488	91.96	gold quality
cerebellum	UBERON:0002037	91.59	gold quality
saliva-secreting gland	UBERON:0001044	91.51	gold quality
tibial nerve	UBERON:0001323	91.44	gold quality
body of stomach	UBERON:0001161	91.30	gold quality
apex of heart	UBERON:0002098	91.22	gold quality
thyroid gland	UBERON:0002046	91.12	gold quality
gastrocnemius	UBERON:0001388	90.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22
E-MTAB-4850	no	8.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting PICK1, 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-3667-3P	99.99	67.17	1636
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-9900	96.06	65.48	557

Literature-anchored findings (GeneRIF, showing 40)

• binding with glutamate receptor subtype (PMID:11891216)
• The PICK1 rs3952 polymorphism was genotyped in schizophrenia and controls. Results demonstrated that the PICK1 rs3952 genotype and allele distribution was significantly different between the two groups. (PMID:15305146)
• PICK-1 could be involved in the regulation of both adherens and tight junctions in epithelial cells (PMID:15811349)
• In a case-control association study, an association of the PICK1 gene with schizophrenia (SZ) was seen, which is more prominent in disorganized SZ. Findings implicating PICK1 are consistent with a role for D-serine in the disease. (PMID:16314870)
• polymorphisms of the PICK1 gene identified thus far are unlikely to contribute to genetic susceptibility to schizophrenia in the Japanese population (PMID:17367885)
• findings suggest that the PICK1 gene may be implicated in the susceptibility to spontaneous relapse of methamphetamine psychosis and that, as an intracellular adapter protein, PICK1 may play a role in the pathophysiology of methamphetamine psycho (PMID:17606663)
• PICK1 synaptic targeting requires direct interaction between the PDZ domain and lipid membranes (PMID:17914463)
• KRIP6 regulates kainate receptors by inhibiting PICK1 modulation via competition or a mutual blocking effect (PMID:18692513)
• Results describe the first small-molecule inhibitor (FSC231) of the PDZ domain in PICK1, which binds the PICK1 PDZ domain with an affinity similar to that observed for endogenous peptide ligands. (PMID:20018661)
• Protein interacting with C alpha kinase 1 (PICK1) is involved in promoting tumor growth and correlates with poor prognosis of human breast cancer. (PMID:20384629)
• The PICK1 mRNA is elevated in patient with schizophrenia. (PMID:20385472)
• we have identified a homozygous mutation in the PICK1 gene that is associated with globozoospermia in humans (PMID:20562896)
• Neph proteins and PICK1 synergistically regulate cell recognition and contact formation; Binding required dimerization of PICK1, was dependent on PDZ domain protein interactions, and mediated stabilization of Neph1 at the plasma membrane. (PMID:21690291)
• PICK1 is a suppressor of spinocerebellar ataxia 3-associated neurodegeneration. (PMID:21949352)
• The binding affinities of all major PICK1 interacting proteins are reported and the effects of PICK1 mutations on these interactions are described. (PMID:22275068)
• Our data suggest a selective role of PICK1 in clustering and reducing the recycling rates of PDZ domain binding partners sorted to the Rab11-dependent recycling pathway. (PMID:22303009)
• Family-based association study failed to observe a statistically significant association for any of the genotyped SNPs in the PICK1 gene and attention-deficit hyperactivity disorder. (PMID:22436349)
• PICK1 increases caveolin-mediated endocytosis, ubiquitination and degradation of TGF-beta type I receptor. (PMID:22710801)
• C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1-PKCalpha complex and cerebellar plasticity. (PMID:24358315)
• PICK1 promotes Ago2 localization at endosomal compartments in neuronal dendrites and inhibits Ago2 function in translational repression following neuronal stimulation. (PMID:24723684)
• These data indicate that Pick1 is involved in regulating the cell-cell junction in epithelial cells. (PMID:24937449)
• Data indicate three principal binding modes can account for protein interacting with C-kinase 1 (PICK1) PDZ domains binding specificity. (PMID:25023278)
• PICK1 domain ACT links PICK1-associated vesicles to a motility factor, likely myosin, but, contrary to previous reports, PICK1 neither binds nor inhibits Arp2/3 complex. (PMID:25657323)
• Unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. (PMID:26073603)
• We propose that PICK1 negatively regulates neoplastic infiltration of astrocytic tumors and that manipulation of PICK1 is an attractive possibility for therapeutic intervention (PMID:26466675)
• This study defines a novel mechanism whereby elevated [Ca(2+)] induced by NMDA receptor activation modulates Ago2 and miRNA activity via PICK1. Our work suggests a Ca(2+)-dependent process to regulate miRNA activity in neurons in response to the induction of long-term depression. (PMID:28404816)
• this is the first study to indicate that PICK1 polymorphisms may associate with cognitive functions in schizophrenic patients. (PMID:28507309)
• Our results demonstrate that downregulation of PICK1 elicited by miR-210-3p overexpression activates the TGF-b pathway, which further promotes bone metastasis in PCa, indicating that the miR- 210-3p/PICK1/TGF-b signalling axis plays an important role in PCa bone metastasis. (PMID:28697177)
• PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis. (PMID:28855251)
• PICK1 plays a pivotal role in sepsis-induced acute lung injury by regulating glutathione synthesis via affecting the substrate-specific subunit of lung cystine/glutamate transporter, xCT (PMID:29471107)
• Coincident with the loss of PICK1 by GBF1-activated ARF1, CDC42 recruitment leads to the activation of IRSp53 and the ARP2/3 complex, resulting in a burst of F-actin polymerisation potentially powering scission. (PMID:29743604)
• Study has demonstrated that ARX is a novel substrate of PRKCA, with phosphorylation at serine 174, and that the c-terminal region of ARX required to bind PICK1. Binding causes a shift in PICK1 subcellular localization to the nucleus to co-locate with the ARX protein, and truncation of this C-terminal region leads to the same loss of transcriptional activation as S174A mutant. (PMID:30419043)
• Arf1, AP1, and PICK1 are key coordinators of actin polymerization. (PMID:31740529)
• A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain. (PMID:32352640)
• PICK1 Controls Activity-Dependent Synaptic Vesicle Cargo Retrieval. (PMID:33113376)
• Association of PICK1 and BDNF variations with increased risk of methamphetamine dependence among Iranian population: a case-control study. (PMID:33499851)
• Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer. (PMID:33660148)
• PICK1 Deficiency Exacerbates Sepsis-Associated Acute Kidney Injury. (PMID:34307672)
• Coding variants identified in patients with diabetes alter PICK1 BAR domain function in insulin granule biogenesis. (PMID:35077398)
• The Scaffold Protein PICK1 as a Target in Chronic Pain. (PMID:35455935)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pick1	ENSDARG00000071152
mus_musculus	Pick1	ENSMUSG00000068206
rattus_norvegicus	Pick1	ENSRNOG00000011507
drosophila_melanogaster	PICK1	FBGN0032447
caenorhabditis_elegans		WBGENE00013317

Paralogs (2): ARFIP2 (ENSG00000132254), ARFIP1 (ENSG00000164144)

Protein

Protein identifiers

PRKCA-binding protein — Q9NRD5 (reviewed: Q9NRD5)

Alternative names: Protein interacting with C kinase 1, Protein kinase C-alpha-binding protein

All UniProt accessions (6): Q9NRD5, E7EX80, F6TII1, F6V107, F6V3V1, F6VY12

UniProt curated annotations — full annotation on UniProt →

Function. Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.

Subunit / interactions. Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR. Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition. Interacts with SORCS3.

Subcellular location. Cytoplasm. Perinuclear region. Membrane. Postsynaptic density. Synapse. Synaptosome. Cytoskeleton.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors. Palmitoylation on Cys-413 is essential for long-term synaptic depression (LTD).

Domain organisation. The AH domain mediates binding to F-actin. The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a ‘closed’ formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRD5-1	1	yes
Q9NRD5-2	2

RefSeq proteins (3): NP_001034672, NP_001034673, NP_036539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR010504	AH_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR030798	Arfaptin_fam	Family
IPR036034	PDZ_sf	Homologous_superfamily
IPR037959	PICK1_BAR	Domain

Pfam: PF00595, PF06456

UniProt features (23 total): strand 5, sequence conflict 3, domain 2, splice variant 2, mutagenesis site 2, helix 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2GZV	X-RAY DIFFRACTION	1.12
6AR4	X-RAY DIFFRACTION	1.69
6BJO	X-RAY DIFFRACTION	1.75
6BJN	X-RAY DIFFRACTION	2.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRD5-F1	81.30	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.

Ligand- & substrate-binding residues (2): 44; 46

Post-translational modifications (2): 82, 413

Mutagenesis-validated functional residues (2):

Position	Phenotype
27–28	abolishes interaction with other proteins, but not with itself.
27	abolishes interaction with gria2, but not with prkca.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors

MSigDB gene sets: 220 (showing top): GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_NEURON_MATURATION, GOBP_INSULIN_SECRETION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (15): positive regulation of receptor internalization (GO:0002092), protein phosphorylation (GO:0006468), intracellular protein transport (GO:0006886), obsolete monoamine transport (GO:0015844), glial cell development (GO:0021782), regulation of Arp2/3 complex-mediated actin nucleation (GO:0034315), negative regulation of Arp2/3 complex-mediated actin nucleation (GO:0034316), cellular response to decreased oxygen levels (GO:0036294), cellular response to glucose starvation (GO:0042149), receptor clustering (GO:0043113), neuronal ion channel clustering (GO:0045161), regulation of insulin secretion (GO:0050796), long-term synaptic depression (GO:0060292), dendritic spine organization (GO:0097061), dendritic spine maintenance (GO:0097062)

GO Molecular Function (12): G protein-coupled receptor binding (GO:0001664), protein kinase C binding (GO:0005080), signaling receptor binding (GO:0005102), phospholipid binding (GO:0005543), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), metal ion binding (GO:0046872), actin filament binding (GO:0051015), Arp2/3 complex binding (GO:0071933), membrane curvature sensor activity (GO:0140090), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), postsynaptic density (GO:0014069), endocytic vesicle membrane (GO:0030666), trans-Golgi network membrane (GO:0032588), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Trafficking of AMPA receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
cytoplasm	3
Arp2/3 complex-mediated actin nucleation	2
lipid binding	2
protein-containing complex binding	2
presynapse	2
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
phosphorylation	1
protein modification process	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
glial cell differentiation	1
cell development	1
regulation of actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
negative regulation of actin nucleation	1
response to decreased oxygen levels	1
cellular response to oxygen levels	1
cellular response to starvation	1
plasma membrane	1
protein localization to membrane	1
neuron maturation	1
membrane organization	1
insulin secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
regulation of synaptic plasticity	1
negative regulation of synaptic transmission	1
postsynapse organization	1
neuron projection organization	1
cellular component maintenance	1
dendritic spine organization	1
signaling receptor binding	1
protein kinase binding	1
cation binding	1
actin binding	1

Protein interactions and networks

STRING

2001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PICK1	GRIA2	P42262	999
PICK1	PRKCA	P17252	993
PICK1	GRIA3	P42263	982
PICK1	GRIP1	Q9Y3R0	972
PICK1	DLG4	P78352	962
PICK1	SRR	Q9GZT4	918
PICK1	ICA1	P78506	914
PICK1	GOPC	Q9HD26	894
PICK1	GRIP2	Q9C0E4	891
PICK1	GRM7	Q14831	883
PICK1	GRIA1	P42261	861
PICK1	SORCS3	Q9UPU3	813
PICK1	ASIC2	Q16515	812
PICK1	SLC6A3	Q01959	802
PICK1	GRIK2	Q13002	792

IntAct

1494 interactions, top by confidence:

A	B	Type	Score
PICK1	NECTIN1	psi-mi:“MI:0915”(physical association)	0.590
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
ATP6AP2	ATP6V1C1	psi-mi:“MI:0914”(association)	0.530
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
DPEP1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
RASSF7	TARSL2	psi-mi:“MI:0914”(association)	0.350
TCP10L	RNF40	psi-mi:“MI:0914”(association)	0.350
MAGEA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350
PICK1	AKAP9	psi-mi:“MI:0915”(physical association)	0.000
PICK1	MAP3K4	psi-mi:“MI:0915”(physical association)	0.000
PICK1	NEFL	psi-mi:“MI:0915”(physical association)	0.000
PICK1	UACA	psi-mi:“MI:0915”(physical association)	0.000
PICK1	SNRNP70	psi-mi:“MI:0915”(physical association)	0.000
PICK1	SPTBN1	psi-mi:“MI:0915”(physical association)	0.000
PICK1	TMF1	psi-mi:“MI:0915”(physical association)	0.000
PICK1	EIF3CL	psi-mi:“MI:0915”(physical association)	0.000
FMR1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
TRAF3IP1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
ZFHX3	PICK1	psi-mi:“MI:0915”(physical association)	0.000
LMO3	PICK1	psi-mi:“MI:0915”(physical association)	0.000
USP2	PICK1	psi-mi:“MI:0915”(physical association)	0.000
PICK1	PKNOX2	psi-mi:“MI:0915”(physical association)	0.000
CEP89	PICK1	psi-mi:“MI:0915”(physical association)	0.000
OSGIN1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
PRPF18	PICK1	psi-mi:“MI:0915”(physical association)	0.000
MTG1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
PICK1	RPIA	psi-mi:“MI:0915”(physical association)	0.000
ZNF624	PICK1	psi-mi:“MI:0915”(physical association)	0.000
ARHGEF5	PICK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (617): PICK1 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), EPHA7 (Affinity Capture-MS), UACA (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), ICA1L (Affinity Capture-MS), ICA1 (Affinity Capture-MS), KLHL11 (Affinity Capture-MS), CEP89 (Affinity Capture-MS), FAM117A (Affinity Capture-MS), GNPTAB (Affinity Capture-MS), ITGA6 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B7YDZ4, B1H267, B3STP6, O14243, O43150, O97902, P34445, P40531, P47057, P91124, Q09746, Q10253, Q1AAU6, Q2KJA1, Q2KJB5, Q2T9M1, Q3ZBM5, Q4R7Q5, Q54XE8, Q5PPZ5, Q5R613, Q5REH1, Q62083, Q62419, Q68FW8, Q6CTQ0, Q6FPT9, Q6NRL2, Q6P8X1, Q75C43, Q7SIG6, Q7XPJ0, Q80ZJ7, Q86XE0, Q8IVI9, Q99961, Q9C6C3, Q9D8U8, Q9EP80, Q9FG38

Diamond homologs: B1WAP7, B5DF45, B6CJY4, B6CJY5, E2QYC9, F1MAD2, G2Q0E2, O14640, O14641, O14910, O19132, O35274, O35889, O55164, O60106, O70263, O74747, O75970, O88951, O88952, P10862, P15918, P15919, P29475, P43254, P51140, P51141, P51142, P54792, P57105, P70196, P93471, Q05AS8, Q0P5F3, Q13425, Q17RB8, Q1L5Z9, Q28DL4, Q29498, Q2KIB6

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PICK1	“up-regulates activity”	BNC1	relocalization
PICK1	“up-regulates activity”	ASIC1	relocalization
PICK1	“up-regulates activity”	PRKCA	binding
UNC5A	“up-regulates activity”	PICK1	binding
RAB39B	“up-regulates activity”	PICK1	binding
PICK1	“up-regulates activity”	GRIA2	binding
PICK1	“up-regulates activity”	AMPA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2313 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38057744:C:CA	acceptor_gain	1.0000
22:38059232:AGC:A	acceptor_gain	1.0000
22:38059233:GCG:G	acceptor_gain	1.0000
22:38059233:GCGGA:G	acceptor_gain	1.0000
22:38064999:CAGGT:C	acceptor_loss	1.0000
22:38065000:A:T	acceptor_loss	1.0000
22:38065001:G:A	acceptor_loss	1.0000
22:38067702:AGGG:A	acceptor_gain	1.0000
22:38067703:GGGG:G	acceptor_gain	1.0000
22:38069026:C:A	acceptor_gain	1.0000
22:38069029:TCAGT:T	acceptor_loss	1.0000
22:38069030:CAG:C	acceptor_loss	1.0000
22:38069031:A:AG	acceptor_gain	1.0000
22:38069031:AGT:A	acceptor_gain	1.0000
22:38069032:G:GA	acceptor_gain	1.0000
22:38069032:GT:G	acceptor_gain	1.0000
22:38069032:GTG:G	acceptor_gain	1.0000
22:38069032:GTGT:G	acceptor_gain	1.0000
22:38069032:GTGTT:G	acceptor_gain	1.0000
22:38069119:AATGG:A	donor_loss	1.0000
22:38069120:ATG:A	donor_gain	1.0000
22:38069120:ATGG:A	donor_loss	1.0000
22:38069121:TGGT:T	donor_loss	1.0000
22:38069123:G:GG	donor_gain	1.0000
22:38069123:GTGA:G	donor_loss	1.0000
22:38069124:T:A	donor_loss	1.0000
22:38070833:GACA:G	acceptor_loss	1.0000
22:38070835:CAG:C	acceptor_loss	1.0000
22:38070836:AGATG:A	acceptor_gain	1.0000
22:38070837:GATGG:G	acceptor_gain	1.0000

AlphaMissense

2721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38059292:G:A	G34R	1.000
22:38059292:G:C	G34R	1.000
22:38059292:G:T	G34W	1.000
22:38059293:G:A	G34E	1.000
22:38059293:G:T	G34V	1.000
22:38059298:A:C	S36R	1.000
22:38059300:C:A	S36R	1.000
22:38059300:C:G	S36R	1.000
22:38059302:T:A	I37N	1.000
22:38059305:G:A	G38E	1.000
22:38059307:G:A	G39R	1.000
22:38059307:G:C	G39R	1.000
22:38059308:G:A	G39E	1.000
22:38059311:G:A	G40E	1.000
22:38059341:T:A	V50D	1.000
22:38065005:T:C	F53L	1.000
22:38065007:T:A	F53L	1.000
22:38065007:T:G	F53L	1.000
22:38065047:G:C	G67R	1.000
22:38065048:G:A	G67D	1.000
22:38065048:G:T	G67V	1.000
22:38065050:G:C	D68H	1.000
22:38065051:A:T	D68V	1.000
22:38065057:T:G	I70S	1.000
22:38067722:T:G	Y101D	1.000
22:38069049:G:C	K122N	1.000
22:38069049:G:T	K122N	1.000
22:38069050:C:G	H123D	1.000
22:38069054:G:C	R124P	1.000
22:38069095:G:C	G138R	1.000

dbSNP variants (sampled 300 via entrez): RS1000186760 (22:38071832 G>A), RS1000382147 (22:38066073 T>A), RS1000392814 (22:38060852 G>A,C), RS1000444976 (22:38060532 C>T), RS1000661216 (22:38057078 C>G), RS1000732221 (22:38066386 C>T), RS1000857052 (22:38074408 C>G,T), RS1000950099 (22:38056152 G>C), RS1001115223 (22:38062857 CTTGTCACA>C), RS1001118651 (22:38063148 T>C), RS1001175932 (22:38060511 T>TC), RS1001178460 (22:38055508 G>A), RS1001504439 (22:38066686 C>T), RS1001556799 (22:38066499 T>G), RS1001606398 (22:38061100 G>C)

Disease associations

OMIM: gene MIM:605926 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility due to globozoospermia	Supportive	Autosomal recessive

Mondo (1): male infertility due to globozoospermia (MONDO:0015746)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003435_15	Body fat percentage	3.000000e-09
GCST003435_29	Body fat percentage	1.000000e-06
GCST003435_37	Body fat percentage	9.000000e-08
GCST003435_9	Body fat percentage	2.000000e-07
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST90002395_620	Mean platelet volume	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007800	body fat percentage
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2076369	Toxicity	3	methamphetamine	Psychotic Disorder;Substance-Related Disorders
rs713729	Other	3	methamphetamine	Substance-Related Disorders

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs713729	PICK1	3	4.00	1	methamphetamine
rs2076369	PICK1	3	2.25	1	methamphetamine

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment, decreases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	increases reaction, affects binding	1
ICG 001	increases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Methamphetamine	increases response to substance	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Vanadium	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8SK	Ubigene HCT 116 PICK1 KO	Cancer cell line	Male
CVCL_E0KF	Ubigene HeLa PICK1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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