GOPC

Summary

GOPC (golgi associated PDZ and coiled-coil motif containing, HGNC:17643) is a protein-coding gene on chromosome 6q22.1, encoding Golgi-associated PDZ and coiled-coil motif-containing protein (Q9HD26). Plays a role in intracellular protein trafficking and degradation.

This gene encodes a Golgi protein with a PDZ domain. The PDZ domain is globular and proteins which contain them bind other proteins through short motifs near the C-termini. Mice which are deficient in the orthologous protein have globozoospermia and are infertile. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 57120 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 61
• Clinical variants (ClinVar): 47 total
• Druggable target: yes
• MANE Select transcript: NM_020399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17643
Approved symbol	GOPC
Name	golgi associated PDZ and coiled-coil motif containing
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ94G16.2, PIST, FIG, GOPC1, CAL
Ensembl gene	ENSG00000047932
Ensembl biotype	protein_coding
OMIM	606845
Entrez	57120

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000052569, ENST00000368498, ENST00000535237, ENST00000887825, ENST00000887826, ENST00000887827, ENST00000887828, ENST00000887829, ENST00000937772, ENST00000937773, ENST00000964024, ENST00000964025

RefSeq mRNA: 2 — MANE Select: NM_020399 NM_001017408, NM_020399

CCDS: CCDS34523, CCDS5117

Canonical transcript exons

ENST00000368498 — 9 exons

Exon	Start	End
ENSE00000762780	117573467	117573632
ENSE00000762781	117575177	117575352
ENSE00000840039	117578900	117579064
ENSE00001017893	117560269	117563384
ENSE00001371009	117577448	117577471
ENSE00001931189	117602004	117602511
ENSE00003526662	117566854	117567034
ENSE00003532661	117570860	117570955
ENSE00003551288	117569572	117569736

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.5626 / max 293.8358, expressed in 1803 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75290	24.5444	1803
75291	0.5970	351
75289	0.3690	204
75288	0.0522	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.91	gold quality
epithelial cell of pancreas	CL:0000083	96.49	gold quality
parietal pleura	UBERON:0002400	94.24	gold quality
visceral pleura	UBERON:0002401	93.96	gold quality
secondary oocyte	CL:0000655	93.66	gold quality
germinal epithelium of ovary	UBERON:0001304	92.81	gold quality
middle temporal gyrus	UBERON:0002771	92.60	gold quality
upper arm skin	UBERON:0004263	92.43	gold quality
tendon of biceps brachii	UBERON:0008188	92.22	gold quality
oocyte	CL:0000023	92.00	gold quality
calcaneal tendon	UBERON:0003701	91.97	gold quality
endometrium	UBERON:0001295	91.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.65	gold quality
tendon	UBERON:0000043	91.47	gold quality
palpebral conjunctiva	UBERON:0001812	91.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.28	gold quality
cerebellar vermis	UBERON:0004720	91.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.91	gold quality
cortical plate	UBERON:0005343	90.91	gold quality
stromal cell of endometrium	CL:0002255	90.67	gold quality
thymus	UBERON:0002370	90.43	gold quality
myocardium	UBERON:0002349	90.40	gold quality
left ventricle myocardium	UBERON:0006566	90.22	gold quality
layer of synovial tissue	UBERON:0007616	90.13	gold quality
skin of hip	UBERON:0001554	89.94	gold quality
urethra	UBERON:0000057	89.90	gold quality
eye	UBERON:0000970	89.68	gold quality
uterus	UBERON:0000995	89.63	gold quality
synovial joint	UBERON:0002217	89.49	gold quality
ventricular zone	UBERON:0003053	89.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.41
E-GEOD-124858	no	427.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting GOPC, 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-6740-5P	100.00	65.64	932
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
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-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 23)

• The FIG-ROS locus encodes for an in-frame fusion protein with a constitutively active kinase activity, suggesting that FIG-ROS may act as an oncogene. (PMID:12661006)
• CAL retains CFTR in the cell and targets CFTR for degradation. (PMID:14570915)
• modulates beta1AR intracellular trafficking (PMID:15358775)
• golgin-160 assosiates in an isoform-specific manner with the Golgi-associated protein PIST (PMID:15951434)
• intracellular sorting of the somatostatin receptor subtype 5 is regulated by interactions with PDZ domain proteins PIST/GOPC and PDZK1 (PMID:16012170)
• Our discoveries provide insight into the specific interaction of the GOPC PDZ domain with the C-terminal peptide of Nlg and also provide a general insight about the possible binding mode of the interaction of Nlg with other PDZ domain-containing proteins. (PMID:16882988)
• CAL is a negative regulator of DeltaF508-CFTR cell-surface expression (PMID:17158866)
• The cystic fibrosis-associated ligand (CAL) PDZ domain of the C-terminus of cystic fibrosis-associated conductance regulator (CFTR) is competitively involved with PDZ proteins Na+/H+ exchanger-3 regulatory factors NHERF1 and NHERF2. (PMID:18754678)
• Syntaxin 6 and CAL mediate the degradation of the cystic fibrosis transmembrane conductance regulator (PMID:20130090)
• establish CAL inhibitors as founding members of a class of CFTR “stabilizers” specifically designed to reduce DeltaF508-CFTR post-endocytic breakdown (PMID:21105033)
• crystals of CAL PDZ domain diffracted to 1.4 A resolution (PMID:21543871)
• The coiled-coil domain of PIST was then purified to homogeneity and crystallized at 293 K. Finally, X-ray diffraction data were collected to a resolution of 4.0 A from a crystal belonging to the hexagonal space group P6(2)22 or P6(4)22. (PMID:23545662)
• Data indicate that E3 ubiquitin ligase MARCH2 co-immunoprecipitated and co-localized with CAL and syntaxin 6 (STX6), and show the ubiquitination of CFTR by MARCH2. (PMID:23818989)
• FIG-ROS fusion protein, which is found in a subset of intrahepatic cholangiocarcinoma patients, accelerates cholangiocarcinogenesis. (PMID:24154728)
• Stereochemical preferences modulate affinity and selectivity among CAL PDZ domain protein variants that bind CFTR. (PMID:24210758)
• None of 268 gliomas analysed showed the FIG-ROS1(L) rearrangement. (PMID:24999209)
• Six out of 65 (9%) BTC patients were positive for the FIG-ROS1 fusion, comprising two out of 14 (14%) gallbladder carcinoma (GBC) patients and four out of 25 (16%) extrahepatic cholangiocarcinoma (ECC) patients. (PMID:25231053)
• Our data suggest that PIST contributes to the fine-tuning of b1AR sorting both during biosynthetic and postendocytic trafficking (PMID:25614626)
• CAL overexpression retards B2AR expression in Golgi apparatus and reduces the receptor expression in the plasma membrane. (PMID:25876703)
• CAL can regulate the anterograde trafficking, the internalization as well as the signaling of CRFR1 via modulating the post-translational modifications that the receptor undergoes at the Golgi apparatus. (PMID:26115868)
• PIST, a Golgi-associated PDZ domain-containing protein, interacts with PCDH15 in the plasma membrane. (PMID:27867666)
• GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors. (PMID:31626289)
• The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic beta-cells. (PMID:33359402)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gopc	ENSDARG00000023117
mus_musculus	Gopc	ENSMUSG00000019861
rattus_norvegicus	Gopc	ENSRNOG00000000408
caenorhabditis_elegans	gopc-1	WBGENE00014101

Protein

Protein identifiers

Golgi-associated PDZ and coiled-coil motif-containing protein — Q9HD26 (reviewed: Q9HD26)

Alternative names: CFTR-associated ligand, Fused in glioblastoma, PDZ protein interacting specifically with TC10

All UniProt accessions (2): Q9HD26, F5H1Y4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in intracellular protein trafficking and degradation. May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels. May also regulate the intracellular trafficking of the ADR1B receptor. May play a role in autophagy. Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR. Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes.

Subunit / interactions. Homooligomer. Interacts with FZD5. Interacts with FZD8. Interacts with GRID2 and BECN1. Interacts with CSPG5. Interacts with CLCN3. Interacts with STX6. Interacts with CFTR. Interacts with ASIC3. Interacts with GOLGA3. Interacts with NLGN1. Interacts with RHOQ. Interacts with MARCHF2; the interaction leads to CFTR ubiquitination and degradation. Interacts with ADRB1. May interact with CACNG2. Interacts with CCDC62. (Microbial infection) Interacts with C.rodentium and E.coli (strain Sakai) NleG8.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network membrane. Synapse. Postsynaptic density. Cell projection. Dendrite.

Tissue specificity. Ubiquitously expressed.

Disease relevance. A chromosomal aberration involving GOPC is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which has a constitutive receptor tyrosine kinase activity.

Domain organisation. The PDZ domain mediates interactions with FZD5, FZD8, ASIC3, GRID2, CLCN3. Also mediates interaction with CFTR and ADRB1. The coiled-coil region probably mediates association to membranes, targeting to the Golgi, and interactions with GOLGA3, and STX6. May also mediate interaction with RHOQ.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HD26-1	1	yes
Q9HD26-2	2
Q9HD26-3	3

RefSeq proteins (2): NP_001017408, NP_065132* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR038879	GOPC	Family

Pfam: PF00595

UniProt features (26 total): strand 8, mutagenesis site 5, helix 3, splice variant 3, initiator methionine 1, chain 1, domain 1, region of interest 1, coiled-coil region 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4JOK	X-RAY DIFFRACTION	1.09
4JOE	X-RAY DIFFRACTION	1.14
4JOF	X-RAY DIFFRACTION	1.2
4JOJ	X-RAY DIFFRACTION	1.2
4NMP	X-RAY DIFFRACTION	1.3
4JOR	X-RAY DIFFRACTION	1.34
7JZQ	X-RAY DIFFRACTION	1.35
5K4F	X-RAY DIFFRACTION	1.36
4E34	X-RAY DIFFRACTION	1.4
4E35	X-RAY DIFFRACTION	1.4
4NMO	X-RAY DIFFRACTION	1.4
4NMQ	X-RAY DIFFRACTION	1.4
4NMT	X-RAY DIFFRACTION	1.4
4NMV	X-RAY DIFFRACTION	1.4
4Q6S	X-RAY DIFFRACTION	1.45
4JOG	X-RAY DIFFRACTION	1.47
4JOH	X-RAY DIFFRACTION	1.47
4K6Y	X-RAY DIFFRACTION	1.48
4K75	X-RAY DIFFRACTION	1.5
7JZR	X-RAY DIFFRACTION	1.54
4NMR	X-RAY DIFFRACTION	1.55
7JZO	X-RAY DIFFRACTION	1.61
6V84	X-RAY DIFFRACTION	1.64
4NMS	X-RAY DIFFRACTION	1.7
5IC3	X-RAY DIFFRACTION	1.7
6OV7	X-RAY DIFFRACTION	1.71
4K76	X-RAY DIFFRACTION	1.75
4JOP	X-RAY DIFFRACTION	1.8
4K78	X-RAY DIFFRACTION	1.8
6XNJ	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HD26-F1	70.11	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 419–420 (breakpoint for translocation to form gopc-ros1 fusion protein)

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (5):

Position	Phenotype
175	no effect on subcellular location; when associated with v-182; v-189 and v-196.
182	no effect on subcellular location; when associated with v-175; v-189 and v-196.
189	no effect on subcellular location; when associated with v-175; v-182 and v-196.
196	no effect on subcellular location; when associated with v-175; v-182 and v-189.
216–404	abolishes interaction with marchf2.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5627083	RHO GTPases regulate CFTR trafficking
R-HSA-9013406	RHOQ GTPase cycle

MSigDB gene sets: 188 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_APICAL_PROTEIN_LOCALIZATION, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, TGCGCANK_UNKNOWN, GOCC_VACUOLAR_MEMBRANE, TGCACTT_MIR519C_MIR519B_MIR519A, TATTATA_MIR374, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (6): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi to plasma membrane transport (GO:0006893), negative regulation of anion channel activity (GO:0010360), protein transport (GO:0015031), apical protein localization (GO:0045176), negative regulation of protein localization to cell surface (GO:2000009)

GO Molecular Function (4): identical protein binding (GO:0042802), transmembrane transporter binding (GO:0044325), molecular sequestering activity (GO:0140313), protein binding (GO:0005515)

GO Cellular Component (13): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), membrane (GO:0016020), trans-Golgi network transport vesicle (GO:0030140), dendrite (GO:0030425), Golgi-associated vesicle membrane (GO:0030660), protein-containing complex (GO:0032991), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase Effectors	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
intracellular protein localization	2
protein binding	2
bounding membrane of organelle	2
Golgi-associated vesicle	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
monoatomic anion channel activity	1
negative regulation of ion transmembrane transporter activity	1
negative regulation of anion transmembrane transport	1
transport	1
establishment of protein localization	1
protein localization to cell surface	1
negative regulation of protein localization	1
regulation of protein localization to cell surface	1
molecular_function	1
binding	1
Golgi apparatus	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
transport vesicle	1
clathrin-coated vesicle	1
neuron projection	1
dendritic tree	1
cytoplasmic vesicle membrane	1
cellular_component	1
cell junction	1

Protein interactions and networks

STRING

1850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GOPC	RHOQ	P17081	989
GOPC	STX6	O43752	967
GOPC	CFTR	P13569	937
GOPC	ROS1	P08922	902
GOPC	PICK1	Q9NRD5	894
GOPC	CD46	P15529	890
GOPC	NHERF1	O14745	866
GOPC	GOLGA3	Q08378	849
GOPC	BECN1	Q14457	835
GOPC	SPATA16	Q9BXB7	813
GOPC	NHERF2	Q15599	783
GOPC	SLC34A2	O95436	768
GOPC	GOLPH3	Q9H4A6	746
GOPC	ADRB1	P08588	734
GOPC	RET	P07949	720

IntAct

662 interactions, top by confidence:

A	B	Type	Score
GOPC	CFTR	psi-mi:“MI:0915”(physical association)	0.770
ZBTB49	GOPC	psi-mi:“MI:0915”(physical association)	0.740
GOPC	ZBTB49	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SSNA1	GOPC	psi-mi:“MI:0915”(physical association)	0.670
GOPC	VTN	psi-mi:“MI:0915”(physical association)	0.670
GOPC	FOSL2	psi-mi:“MI:0915”(physical association)	0.670
GOPC	MYOCD	psi-mi:“MI:0915”(physical association)	0.670
MYOCD	GOPC	psi-mi:“MI:0915”(physical association)	0.670
GOPC	SSNA1	psi-mi:“MI:0915”(physical association)	0.670
VTN	GOPC	psi-mi:“MI:0915”(physical association)	0.670
FOSL2	GOPC	psi-mi:“MI:0915”(physical association)	0.670
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
GOPC	HEL-S-42	psi-mi:“MI:0915”(physical association)	0.600
HEL-S-42	GOPC	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (438): GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid), GOPC (Two-hybrid)

ESM2 similar proteins: A0PJP4, A0PJT0, A1A600, A2A6T1, A4IFK7, D3YV10, D3ZUQ0, G9G127, P97817, Q08379, Q0IHE5, Q0P4J3, Q17QG3, Q499E4, Q5EBL4, Q5RCR6, Q5RD32, Q5VU43, Q5XIA0, Q5XJA2, Q5ZJA3, Q61043, Q62839, Q6AYA0, Q6DFC2, Q6IP02, Q6NZT2, Q80YF0, Q86X02, Q86YS3, Q8BH60, Q8BQP8, Q8C2K1, Q8IYE1, Q8N4C6, Q91WG2, Q921M4, Q92574, Q969X0, Q96CN9

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

4 interactions.

A	Effect	B	Mechanism
GOPC	down-regulates	CFTR	binding
GOPC	down-regulates	ADRB1	relocalization
GOPC	up-regulates	BECN1	binding
GOLGA3	“up-regulates activity”	GOPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
PI3K Cascade	5	16.6×	1e-03
EPH-ephrin mediated repulsion of cells	6	16.1×	3e-04
Constitutive Signaling by Aberrant PI3K in Cancer	9	13.9×	9e-06
EPH-Ephrin signaling	6	12.1×	1e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	9	10.6×	5e-05
PIP3 activates AKT signaling	10	8.1×	8e-05
RAF/MAP kinase cascade	8	6.0×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	9	36.8×	1e-09
regulation of GTPase activity	5	24.8×	2e-04
cell surface receptor protein tyrosine kinase signaling pathway	13	21.9×	3e-11
ephrin receptor signaling pathway	6	20.0×	7e-05
positive regulation of neuron projection development	11	14.6×	6e-08
protein autophosphorylation	10	14.1×	5e-07
axon guidance	14	12.3×	3e-09
cellular response to retinoic acid	5	11.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1620 predictions. Top by Δscore:

Variant	Effect	Δscore
6:117566848:TTTTA:T	donor_loss	1.0000
6:117566849:TTTA:T	donor_loss	1.0000
6:117566849:TTTAC:T	donor_loss	1.0000
6:117566850:TTA:T	donor_loss	1.0000
6:117566850:TTAC:T	donor_loss	1.0000
6:117566851:TAC:T	donor_loss	1.0000
6:117566851:TACCT:T	donor_loss	1.0000
6:117566852:A:T	donor_loss	1.0000
6:117566853:CCTTG:C	donor_loss	1.0000
6:117566907:C:CT	donor_gain	1.0000
6:117566908:C:CT	donor_gain	1.0000
6:117566912:T:TA	donor_gain	1.0000
6:117567030:CCTCT:C	acceptor_gain	1.0000
6:117567031:CTCT:C	acceptor_gain	1.0000
6:117567031:CTCTC:C	acceptor_gain	1.0000
6:117567032:TCTC:T	acceptor_gain	1.0000
6:117567033:CT:C	acceptor_gain	1.0000
6:117567035:C:CA	acceptor_loss	1.0000
6:117567035:C:CC	acceptor_gain	1.0000
6:117567036:T:A	acceptor_loss	1.0000
6:117567041:C:CT	acceptor_gain	1.0000
6:117567042:A:T	acceptor_gain	1.0000
6:117567047:A:AC	acceptor_gain	1.0000
6:117567047:A:C	acceptor_gain	1.0000
6:117569567:TTTAC:T	donor_loss	1.0000
6:117569568:TTA:T	donor_loss	1.0000
6:117569569:TACC:T	donor_loss	1.0000
6:117569570:A:C	donor_loss	1.0000
6:117569571:C:CT	donor_loss	1.0000
6:117569571:CCT:C	donor_loss	1.0000

AlphaMissense

3016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:117569582:A:G	L356P	1.000
6:117569582:A:T	L356H	1.000
6:117569594:G:T	A352D	1.000
6:117569595:C:G	A352P	1.000
6:117569603:T:C	H349R	1.000
6:117569604:G:C	H349D	1.000
6:117569618:A:G	L344P	1.000
6:117569633:A:T	V339D	1.000
6:117569642:A:T	I336N	1.000
6:117569645:G:T	A335D	1.000
6:117569646:C:G	A335P	1.000
6:117569648:T:A	D334V	1.000
6:117569648:T:C	D334G	1.000
6:117569648:T:G	D334A	1.000
6:117569649:C:G	D334H	1.000
6:117569651:C:A	G333V	1.000
6:117569651:C:T	G333E	1.000
6:117569652:C:A	G333W	1.000
6:117569652:C:G	G333R	1.000
6:117569652:C:T	G333R	1.000
6:117569678:G:T	A324D	1.000
6:117569702:G:A	S316F	1.000
6:117569702:G:T	S316Y	1.000
6:117569703:A:G	S316P	1.000
6:117569705:A:T	I315N	1.000
6:117569708:A:G	L314P	1.000
6:117569708:A:T	L314H	1.000
6:117569711:A:T	I313N	1.000
6:117569717:A:T	V311D	1.000
6:117569732:C:A	G306V	1.000

dbSNP variants (sampled 300 via entrez): RS1000219789 (6:117588954 T>TA), RS1000311768 (6:117562956 A>C), RS1000331348 (6:117595603 TCCTCCTAG>T), RS1000523122 (6:117581201 T>TA), RS1000561789 (6:117602545 C>A,T), RS1000596641 (6:117561108 T>C), RS1000627577 (6:117560781 A>C), RS1000658732 (6:117560405 A>C,G), RS1000719536 (6:117560908 A>C,T), RS1000773190 (6:117568881 T>C), RS1000787655 (6:117562583 G>A), RS1000918472 (6:117575722 A>G), RS1000996151 (6:117576613 A>C), RS1001046484 (6:117561171 T>C), RS1001050419 (6:117585434 G>C)

Disease associations

OMIM: gene MIM:606845 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

61 associations (top):

Study	Trait	p-value
GCST001787_13	Colorectal cancer	3.000000e-06
GCST003542_92	Night sleep phenotypes	2.000000e-06
GCST004731_1	Facial emotion recognition (fearful faces)	1.000000e-06
GCST006061_151	Atrial fibrillation	3.000000e-08
GCST010796_1702	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-19
GCST010796_1703	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-19
GCST010796_1704	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-19
GCST010796_1705	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-19
GCST010796_1706	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-20
GCST010796_1707	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-21
GCST010796_1708	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-22
GCST010796_1709	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-27
GCST010796_1710	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-29
GCST010796_1711	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-25
GCST010796_1712	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-28
GCST010796_1713	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-30
GCST010796_1714	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-34
GCST010796_1715	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-33
GCST010796_1716	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-32
GCST010796_1717	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-28
GCST010796_1718	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-28
GCST010796_1719	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-26
GCST010796_1720	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-24
GCST010796_1721	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-24
GCST010796_1722	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-26
GCST010796_1723	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-26
GCST010796_1724	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-22
GCST010796_1725	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23
GCST010796_1726	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-24
GCST010796_1727	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-23

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1741218 (SINGLE PROTEIN), CHEMBL3885559 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483088 (CHIMERIC PROTEIN)

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

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4783570	KD	490 nM
CHEMBL5177006	KI	2300 nM
CHEMBL5202803	KI	22600 nM

ChEMBL bioactivities

30 potent at pChembl≥5 of 59 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	Kd	6	nM	CHEMBL4756359
7.70	IC50	20	nM	CHEMBL4777388
7.31	Kd	49	nM	CHEMBL4763464
7.06	Kd	87	nM	CHEMBL4789294
6.95	Kd	113	nM	CHEMBL4756115
6.82	IC50	150	nM	CHEMBL4789394
6.82	IC50	150	nM	CHEMBL4779439
6.77	IC50	170	nM	CHEMBL4739952
6.62	IC50	240	nM	CHEMBL4753496
6.57	IC50	270	nM	CHEMBL4795173
6.43	IC50	370	nM	CHEMBL4798520
6.42	IC50	380	nM	CHEMBL4792301
6.40	IC50	400	nM	CHEMBL4752826
6.31	Kd	490	nM	CHEMBL4783570
6.17	IC50	680	nM	CHEMBL4790861
5.82	IC50	1500	nM	CHEMBL4762047
5.80	IC50	1600	nM	CHEMBL4759877
5.75	IC50	1800	nM	CHEMBL4764244
5.66	IC50	2200	nM	CHEMBL4794279
5.64	Ki	2300	nM	CHEMBL5177006
5.62	IC50	2400	nM	CHEMBL4763642
5.60	IC50	2500	nM	CHEMBL4800168
5.44	AC50	3597	nM	CHEMBL1553368
5.43	IC50	3700	nM	CHEMBL4791418
5.39	AC50	4080	nM	CHEMBL1606122
5.37	IC50	4300	nM	CHEMBL4792820
5.13	IC50	7400	nM	CHEMBL4757746
5.10	IC50	7900	nM	CHEMBL4792234
5.10	IC50	8000	nM	CHEMBL4764592
5.00	IC50	1e+04	nM	CHEMBL4758509

PubChem BioAssay actives

28 with measured affinity, of 38 total; 28 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-1-[(2S)-3-(1-benzothiophen-3-yl)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-2-[[2-[2-[2-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]ethoxy]ethoxy]acetyl]amino]-3-sulfanylpropanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]piperidine-2-carbonyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701512: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay	kd	0.0060	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]piperidine-2-carbonyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.0200	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-3-(1-benzothiophen-3-yl)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-2-[[2-[2-[2-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-carbonyl)amino]ethoxy]ethoxy]acetyl]amino]-3-sulfanylpropanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701512: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay	kd	0.0490	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-1-[(2S)-3-(1-benzothiophen-3-yl)-2-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-2-[[2-[2-[2-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]ethoxy]ethoxy]acetyl]amino]-3-sulfanylpropanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701512: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay	kd	0.0870	uM
5-[[3-[[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2R)-1-[[(2S,3R)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2,2-dimethylpropyl]amino]-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxo-3-sulfanylbutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-oxopropyl]carbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1701512: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr by fluorescence polarization based competition assay	kd	0.1130	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.1500	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.1500	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.1700	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.2400	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.2700	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.3700	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.3800	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.4000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(4R,7S,10S,13S,16S,19S,22S,25S,28R)-28-acetamido-7-(3-amino-3-oxopropyl)-13-benzyl-16,19,22,25-tetrakis(3-carbamimidamidopropyl)-10-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27-octaoxo-1,2-dithia-5,8,11,14,17,20,23,26-octazacyclononacosane-4-carbonyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoic acid	1879934: Binding affinity to CAL PDZ domain (unknown origin) assessed as dissociation constant in presence of tris(carboxylethyl)phosphine by fluorescence anisotropy analysis	kd	0.4900	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methyl-3-sulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	0.6800	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	1.5000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	1.6000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-3-naphthalen-1-ylpropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3,3-dimethylbutanoic acid	1701509: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-22 probe by fluorescence polarization based competition assay	ic50	1.8000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-6-(pyridine-3-carbonylamino)hexanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	2.2000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoic acid	1879933: Inhibition of CAL PDZ domain (unknown origin) assessed as inhibition constant by fluorescence polarization competition assay	ki	2.3000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-6-(diaminomethylideneamino)hexanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	2.4000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-6-[(2,2,2-trifluoroacetyl)amino]hexanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	2.5000	uM
(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	3.7000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	4.3000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2R)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	7.4000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-cyclohexylpropanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	7.9000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	8.0000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxybutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3,3-dimethylbutanoic acid	1701508: Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression, affects cotreatment	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4706330	Binding	Binding affinity to C-terminal His6 tagged CAL PDZ domain (unknown origin) expressed in Escherichia coli BL21 incubated for 1 hr using FAM-ANSRWPTSII-OH probe by fluorescence polarization based competition assay	Cyclic Peptidyl Inhibitors against CAL/CFTR Interaction for Treatment of Cystic Fibrosis. — J Med Chem
CHEMBL1963993	Functional	PUBCHEM_BIOASSAY: Fluorescence Polarization with Cer CAL-PDZ Measured in Biochemical System Using Plate Reader - 2109-01_Inhibitor_Dose_DryPowder_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome