CELSR3

Summary

CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3, HGNC:3230) is a protein-coding gene on chromosome 3p21.31, encoding Cadherin EGF LAG seven-pass G-type receptor 3 (Q9NYQ7). Receptor that may have an important role in cell/cell signaling during nervous system formation.

This gene belongs to the flamingo subfamily, which is included in the cadherin superfamily. The flamingo cadherins consist of nonclassic-type cadherins that do not interact with catenins. They are plasma membrane proteins containing seven epidermal growth factor-like repeats, nine cadherin domains and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic feature of their subfamily. The encoded protein may be involved in the regulation of contact-dependent neurite growth and may play a role in tumor formation.

Source: NCBI Gene 1951 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 528 total — 13 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3230
Approved symbol	CELSR3
Name	cadherin EGF LAG seven-pass G-type receptor 3
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MEGF2, HFMI1, FMI1, CDHF11, ADGRC3
Ensembl gene	ENSG00000008300
Ensembl biotype	protein_coding
OMIM	604264
Entrez	1951

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 retained_intron, 1 protein_coding

ENST00000164024, ENST00000461362, ENST00000470999, ENST00000498057

RefSeq mRNA: 1 — MANE Select: NM_001407 NM_001407

CCDS: CCDS2775

Canonical transcript exons

ENST00000164024 — 35 exons

Exon	Start	End
ENSE00000877808	48651877	48652048
ENSE00000896593	48652437	48652553
ENSE00000896594	48653002	48653187
ENSE00000896598	48655044	48655201
ENSE00001170603	48653619	48653788
ENSE00001170612	48653878	48654003
ENSE00001170621	48654289	48654452
ENSE00001170638	48655306	48655394
ENSE00001170646	48655736	48655851
ENSE00001170656	48656140	48656365
ENSE00001170666	48656698	48657348
ENSE00001299306	48658887	48662886
ENSE00001521962	48636463	48638232
ENSE00001593724	48650480	48650581
ENSE00001605181	48645443	48645649
ENSE00001615901	48646090	48646257
ENSE00001622089	48651577	48651718
ENSE00001626796	48645035	48645209
ENSE00001678032	48643554	48643677
ENSE00001682094	48649121	48649215
ENSE00001685584	48648719	48648928
ENSE00001691694	48651359	48651479
ENSE00001700810	48644216	48644295
ENSE00001723560	48646763	48646928
ENSE00001746917	48648266	48648461
ENSE00001749029	48650892	48651075
ENSE00001763251	48644716	48644828
ENSE00001776554	48647841	48647996
ENSE00001788364	48645742	48645868
ENSE00003515179	48639674	48640559
ENSE00003524770	48642358	48642467
ENSE00003564588	48642736	48642884
ENSE00003605084	48641324	48641524
ENSE00003622611	48641851	48642009
ENSE00003675312	48642967	48643083

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 94.22.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2736 / max 54.2317, expressed in 440 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42162	1.2736	440

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.22	gold quality
cortical plate	UBERON:0005343	94.03	gold quality
cerebellar hemisphere	UBERON:0002245	93.74	gold quality
cerebellar cortex	UBERON:0002129	93.64	gold quality
ganglionic eminence	UBERON:0004023	93.36	gold quality
cerebellum	UBERON:0002037	92.96	gold quality
pituitary gland	UBERON:0000007	89.81	gold quality
paraflocculus	UBERON:0005351	89.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.78	gold quality
cerebellar vermis	UBERON:0004720	88.67	gold quality
adenohypophysis	UBERON:0002196	88.50	gold quality
right frontal lobe	UBERON:0002810	86.95	gold quality
postcentral gyrus	UBERON:0002581	85.27	gold quality
CA1 field of hippocampus	UBERON:0003881	85.22	gold quality
entorhinal cortex	UBERON:0002728	84.67	gold quality
primary visual cortex	UBERON:0002436	84.52	gold quality
endometrium epithelium	UBERON:0004811	84.43	silver quality
embryo	UBERON:0000922	84.32	gold quality
superior frontal gyrus	UBERON:0002661	84.31	gold quality
parietal lobe	UBERON:0001872	84.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.92	gold quality
frontal cortex	UBERON:0001870	83.77	gold quality
neocortex	UBERON:0001950	83.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.33	gold quality
cerebral cortex	UBERON:0000956	83.02	gold quality
brain	UBERON:0000955	82.62	gold quality
orbitofrontal cortex	UBERON:0004167	82.53	gold quality
middle temporal gyrus	UBERON:0002771	82.45	gold quality
central nervous system	UBERON:0001017	82.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, REST

miRNA regulators (miRDB)

113 targeting CELSR3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 14)

• CELSR3 is one of the core PCP signaling molecules. (PMID:16273260)
• CELSR3 was found to be selectively up-regulated in tumor stellate cells. (PMID:20416094)
• CELSR3 promoter hypermethylation is associated with oral squamous cell carcinoma. (PMID:25374236)
• seven-transmembrane domain receptors Celsr3 and Fzd3, in particular, control the development of most longitudinal tracts in the central nervous system. [Review] (PMID:25813877)
• A moderate positive correlation between CELSR3 and patient age was also evident. (PMID:26838213)
• marked reduction in the prominence of TUJ1 bundles in number, thickness, and length. Our results showed that deregulation of the planar cell polarity genes CELSR3 and FZD3 might disrupt the enteric innervation pattern (PMID:27619161)
• Study identifies four likely Tourette disorder risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). (PMID:28472652)
• CELSR3 copy number variants are associated with Tourette syndrome and implicate cell polarity in pathogenesis. (PMID:30257206)
• Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma. (PMID:33811453)
• Clinical Significance and Underlying Mechanisms of CELSR3 in Metastatic Prostate Cancer Based on Immunohistochemistry, Data Mining, and In Silico Analysis. (PMID:34582697)
• CELSR3 variants are associated with febrile seizures and epilepsy with antecedent febrile seizures. (PMID:34951123)
• Evaluated expression of CELSR3 in oral squamous cell carcinoma is associated with perineural invasion and poor prognosis. (PMID:35165064)
• The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms. (PMID:37224017)
• CELSR3 is a prognostic marker in HNSCC and correlates with immune cell infiltration in the tumor microenvironment. (PMID:38507078)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	celsr3	ENSDARG00000055825
mus_musculus	Celsr3	ENSMUSG00000023473
rattus_norvegicus	Celsr3	ENSRNOG00000053889
drosophila_melanogaster	stan	FBGN0024836
caenorhabditis_elegans		WBGENE00001475
caenorhabditis_elegans	hmr-1	WBGENE00001980
caenorhabditis_elegans	Y52B11A.11	WBGENE00014914

Paralogs (6): CELSR1 (ENSG00000075275), FAT1 (ENSG00000083857), FAT2 (ENSG00000086570), CELSR2 (ENSG00000143126), FAT3 (ENSG00000165323), FAT4 (ENSG00000196159)

Protein

Protein identifiers

Cadherin EGF LAG seven-pass G-type receptor 3 — Q9NYQ7 (reviewed: Q9NYQ7)

Alternative names: Cadherin family member 11, Epidermal growth factor-like protein 1, Flamingo homolog 1, Multiple epidermal growth factor-like domains protein 2

All UniProt accessions (1): Q9NYQ7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor that may have an important role in cell/cell signaling during nervous system formation.

Subcellular location. Cell membrane.

Similarity. Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYQ7-1	1	yes
Q9NYQ7-2	2

RefSeq proteins (1): NP_001398* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000742	EGF	Domain
IPR000832	GPCR_2_secretin-like	Family
IPR001791	Laminin_G	Domain
IPR001879	GPCR_2_extracellular_dom	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR002126	Cadherin-like_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR020894	Cadherin_CS	Conserved_site
IPR032471	AGRL2-4_GAIN_subdom_A	Domain
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR056286	Cadherin_CELSR1-3_9th	Domain
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF00008, PF00028, PF00053, PF01825, PF02210, PF02793, PF16489, PF23592

UniProt features (110 total): disulfide bond 29, domain 21, glycosylation site 15, region of interest 9, topological domain 8, compositionally biased region 8, transmembrane region 7, sequence variant 5, modified residue 4, signal peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NYQ7 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (4): 1963, 2126, 3051, 3097

Disulfide bonds (29): 2110–2122, 2480–2512, 2500–2514, 1379–1390, 1384–1421, 1423–1432, 1439–1450, 1444–1459, 1461–1470, 1479–1490, 1484–1500, 1502–1513, 1693–1719, 1726–1737, 1731–1746, 1748–1757, 1915–1944, 1950–1961, 1955–1970, 1972–1981 …

Glycosylation sites (15): 632, 847, 1182, 1222, 1317, 1327, 1649, 1713, 1770, 2053, 2177, 2196, 2386, 2474, 2506

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_BCELL_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, YY1_Q6, MODULE_66, GOBP_CELL_CELL_ADHESION, SMID_BREAST_CANCER_LUMINAL_B_UP, KMCATNNWGGA_UNKNOWN, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, ACATTCC_MIR1_MIR206, AAAGGGA_MIR204_MIR211, ARGGGTTAA_UNKNOWN, TGACATY_UNKNOWN

GO Biological Process (10): homophilic cell-cell adhesion (GO:0007156), G protein-coupled receptor signaling pathway (GO:0007186), axonogenesis (GO:0007409), dopaminergic neuron axon guidance (GO:0036514), serotonergic neuron axon guidance (GO:0036515), cell-cell adhesion mediated by cadherin (GO:0044331), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), calcium ion binding (GO:0005509), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), adherens junction (GO:0005912), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
signal transduction	2
axon guidance	2
cellular process	2
G protein-coupled receptor activity	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
non-canonical Wnt signaling pathway	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
metal ion binding	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cell-cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CELSR3	FZD3	Q9NPG1	909
CELSR3	FZD9	O00144	858
CELSR3	VANGL2	Q9ULK5	733
CELSR3	FZD6	O60353	723
CELSR3	VANGL1	Q8TAA9	688
CELSR3	PRICKLE2	Q7Z3G6	638
CELSR3	CDH17	Q12864	637
CELSR3	PRICKLE1	Q96MT3	630
CELSR3	PRICKLE3	O43900	629
CELSR3	PRICKLE4	Q2TBC4	605
CELSR3	EGF	P01133	583
CELSR3	DVL1	O14640	535
CELSR3	EMX1	Q04741	533
CELSR3	DVL2	O14641	511
CELSR3	CSF1	P09603	498

IntAct

46 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PSG9	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
ABL1	CELSR3	psi-mi:“MI:0915”(physical association)	0.400
FYN	CELSR3	psi-mi:“MI:0915”(physical association)	0.400
GRB2	CELSR3	psi-mi:“MI:0915”(physical association)	0.400
NCK1	CELSR3	psi-mi:“MI:0915”(physical association)	0.400
CELSR3	TRIP12	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	SPTBN2	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	MCM3AP	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	IFT140	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	PPP1R26	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	CLUH	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	TSPYL4	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	SCAPER	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	RACGAP1	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	UACA	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	SPTBN4	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	SWAP70	psi-mi:“MI:0915”(physical association)	0.370
CELSR3	DST	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): CELSR3 (Affinity Capture-MS), CELSR3 (Biochemical Activity), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), CELSR3 (Affinity Capture-RNA)

ESM2 similar proteins: D3ZE55, O14917, O35161, O95206, Q5DRE1, Q5DRE2, Q5DRE3, Q5DRE4, Q5DRE5, Q5DRE6, Q5DRE7, Q5DRE8, Q5DRE9, Q5DRF0, Q5DRF1, Q5DRF2, Q5DRF3, Q5DRF4, Q5DRF5, Q5JZY3, Q63315, Q6PFX6, Q767I8, Q7TSK3, Q86UP0, Q8BYG9, Q91Y11, Q91Y13, Q91Y20, Q91ZI0, Q9H158, Q9NPG4, Q9NYQ6, Q9NYQ7, Q9P2E7, Q9UJ99, Q9UN72, Q9UN73, Q9UN74, Q9UN75

Diamond homologs: A6QLU6, C0HL12, D4A3T6, E9Q4J9, G5ECX0, G5EDW2, O14514, O35161, O60242, O88278, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P30083, P48960, Q14246, Q2Q421, Q2Q426, Q3UHD1, Q54MC6, Q58Y75, Q59I63, Q5T601, Q5Y4N8, Q61549, Q6F3F9, Q6QNK2, Q7SY09, Q7Z7M1, Q80T32, Q80TR1, Q80TS3, Q80ZF8, Q86SQ3, Q86SQ4, Q8IZF2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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
NCAM signaling for neurite out-growth	6	46.6×	8e-07
Cell surface interactions at the vascular wall	6	16.3×	2e-04
Axon guidance	7	9.0×	1e-03
Nervous system development	7	8.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	13
Uncertain significance	416
Likely benign	54
Benign	23

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2672059	NM_001407.3(CELSR3):c.1574G>A (p.Arg525His)	Likely pathogenic
2672060	NM_001407.3(CELSR3):c.7999G>A (p.Gly2667Ser)	Likely pathogenic
2672061	NM_001407.3(CELSR3):c.6959T>C (p.Val2320Ala)	Likely pathogenic
2672063	NM_001407.3(CELSR3):c.3712C>T (p.Arg1238Cys)	Likely pathogenic
2672064	NM_001407.3(CELSR3):c.7501G>A (p.Glu2501Lys)	Likely pathogenic
2672065	NM_001407.3(CELSR3):c.3142C>T (p.Arg1048Trp)	Likely pathogenic
2672066	NM_001407.3(CELSR3):c.3100G>C (p.Glu1034Gln)	Likely pathogenic
2672067	NM_001407.3(CELSR3):c.9299G>C (p.Gly3100Ala)	Likely pathogenic
2672068	NM_001407.3(CELSR3):c.7423C>T (p.Arg2475Trp)	Likely pathogenic
2672070	NM_001407.3(CELSR3):c.6304G>A (p.Ala2102Thr)	Likely pathogenic
2672071	NM_001407.3(CELSR3):c.5059C>T (p.His1687Tyr)	Likely pathogenic
2672072	NM_001407.3(CELSR3):c.7075C>T (p.Pro2359Ser)	Likely pathogenic
2672074	NM_001407.3(CELSR3):c.8480C>A (p.Thr2827Asn)	Likely pathogenic

SpliceAI

6403 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48641327:T:A	donor_gain	1.0000
3:48641876:A:AC	donor_gain	1.0000
3:48641877:C:CC	donor_gain	1.0000
3:48641877:CT:C	donor_gain	1.0000
3:48642008:GCC:G	acceptor_loss	1.0000
3:48642010:C:CA	acceptor_loss	1.0000
3:48642010:C:CC	acceptor_gain	1.0000
3:48642354:C:CA	donor_gain	1.0000
3:48642727:T:TA	donor_gain	1.0000
3:48642734:A:AC	donor_gain	1.0000
3:48642734:ACCT:A	donor_loss	1.0000
3:48642735:C:CC	donor_gain	1.0000
3:48642880:GGTCC:G	acceptor_gain	1.0000
3:48642881:GTCC:G	acceptor_gain	1.0000
3:48642882:TCC:T	acceptor_gain	1.0000
3:48642883:CC:C	acceptor_gain	1.0000
3:48642883:CCC:C	acceptor_gain	1.0000
3:48642883:CCCTG:C	acceptor_loss	1.0000
3:48642884:CC:C	acceptor_gain	1.0000
3:48642884:CCTGG:C	acceptor_loss	1.0000
3:48642885:C:CC	acceptor_gain	1.0000
3:48642885:C:T	acceptor_gain	1.0000
3:48644214:A:AC	donor_gain	1.0000
3:48644215:C:CC	donor_gain	1.0000
3:48644215:CAGTG:C	donor_gain	1.0000
3:48644293:CAT:C	acceptor_gain	1.0000
3:48644303:C:CT	acceptor_gain	1.0000
3:48644303:C:T	acceptor_gain	1.0000
3:48644305:C:CT	acceptor_gain	1.0000
3:48644309:C:CT	acceptor_gain	1.0000

AlphaMissense

21348 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48645847:C:A	W2495C	1.000
3:48645847:C:G	W2495C	1.000
3:48649178:C:A	W2170C	1.000
3:48649178:C:G	W2170C	1.000
3:48650535:C:A	W2139C	1.000
3:48650535:C:G	W2139C	1.000
3:48655789:T:A	D1563V	1.000
3:48656802:C:G	C1432S	1.000
3:48656802:C:T	C1432Y	1.000
3:48656803:A:T	C1432S	1.000
3:48656928:C:G	C1390S	1.000
3:48656929:A:G	C1390R	1.000
3:48656929:A:T	C1390S	1.000
3:48656946:C:T	C1384Y	1.000
3:48659606:A:G	F1010S	1.000
3:48659831:T:G	D935A	1.000
3:48659832:C:G	D935H	1.000
3:48659837:G:T	A933D	1.000
3:48659952:A:C	Y895D	1.000
3:48660068:G:T	P856Q	1.000
3:48660079:G:C	N852K	1.000
3:48660079:G:T	N852K	1.000
3:48660230:A:G	F802S	1.000
3:48645849:A:G	W2495R	0.999
3:48645849:A:T	W2495R	0.999
3:48646113:A:C	C2480W	0.999
3:48646114:C:G	C2480S	0.999
3:48646114:C:T	C2480Y	0.999
3:48646115:A:G	C2480R	0.999
3:48646115:A:T	C2480S	0.999

dbSNP variants (sampled 300 via entrez): RS1000030494 (3:48659585 C>G), RS1000274401 (3:48643334 C>T), RS1000301493 (3:48644588 G>C), RS1000318600 (3:48637007 T>A), RS1000396998 (3:48637863 A>G), RS1000418842 (3:48644371 A>G), RS1000799645 (3:48664883 G>A), RS1000867523 (3:48656562 C>T), RS1000961186 (3:48664715 T>C), RS1001158005 (3:48656927 G>A), RS1001169723 (3:48664436 G>A), RS1001192368 (3:48658657 A>G), RS1001386145 (3:48649567 C>T), RS1001407361 (3:48649648 G>A,C), RS1001462791 (3:48644510 G>A,C)

Disease associations

OMIM: gene MIM:604264 | disease phenotypes: MIM:137580, MIM:610805, MIM:600057

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (6): Tourette syndrome (MONDO:0007661), autism spectrum disorder (MONDO:0005258), congenital anomalies of kidney and urinary tract 1 (MONDO:0012561), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), hypertrophic cardiomyopathy (MONDO:0005045), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (4): Classic bladder exstrophy (Orphanet:93930), Rare hypertrophic cardiomyopathy (Orphanet:217569), NON RARE IN EUROPE: Tourette syndrome (Orphanet:856), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005141_6	Cognitive ability (MTAG)	3.000000e-09
GCST008549_11	Mental health study participation (provided email address)	4.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST012226_605	Waist circumference adjusted for body mass index	1.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010130	health study participation
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
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
C563661	Renal Hypodysplasia, Nonsyndromic, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adhesion Class GPCRs

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Emodin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

185 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