ATL2

Summary

ATL2 (atlastin GTPase 2, HGNC:24047) is a protein-coding gene on chromosome 2p22.2-p22.1, encoding Atlastin-2 (Q8NHH9). Atlastin-2 (ATL2) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It is a selective cancer dependency (DepMap: 68.7% of cell lines).

Enables identical protein binding activity. Involved in Golgi organization; endoplasmic reticulum tubular network membrane organization; and protein homooligomerization. Located in endoplasmic reticulum tubular network membrane.

Source: NCBI Gene 64225 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• Clinical variants (ClinVar): 109 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 68.7% of screened cell lines
• MANE Select transcript: NM_001135673

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24047
Approved symbol	ATL2
Name	atlastin GTPase 2
Location	2p22.2-p22.1
Locus type	gene with protein product
Status	Approved
Aliases	atlastin2
Ensembl gene	ENSG00000119787
Ensembl biotype	protein_coding
OMIM	609368
Entrez	64225

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000378954, ENST00000402054, ENST00000405384, ENST00000406122, ENST00000416222, ENST00000419554, ENST00000443098, ENST00000449130, ENST00000451483, ENST00000452935, ENST00000456736, ENST00000472097, ENST00000474535, ENST00000477642, ENST00000486927, ENST00000489896, ENST00000651368, ENST00000879827, ENST00000879828, ENST00000879829, ENST00000940194, ENST00000960026

RefSeq mRNA: 10 — MANE Select: NM_001135673 NM_001135673, NM_001308076, NM_001330458, NM_001330459, NM_001330460, NM_001330461, NM_001330462, NM_001330463, NM_001330464, NM_022374

CCDS: CCDS1795, CCDS46260, CCDS77402, CCDS82436, CCDS86831

Canonical transcript exons

ENST00000378954 — 13 exons

Exon	Start	End
ENSE00001479372	38293954	38296113
ENSE00003482089	38343268	38343512
ENSE00003519083	38299256	38299327
ENSE00003526482	38310309	38310447
ENSE00003528446	38377143	38377273
ENSE00003557916	38298144	38298575
ENSE00003568364	38300272	38300328
ENSE00003626551	38318535	38318639
ENSE00003630613	38318885	38319019
ENSE00003653332	38315284	38315334
ENSE00003659498	38313151	38313243
ENSE00003687709	38314608	38314664
ENSE00003786243	38309379	38309506

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9095 / max 358.8404, expressed in 1786 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27870	16.2586	1775
27868	0.8819	363
27869	0.4643	269
27871	0.3047	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.03	gold quality
oocyte	CL:0000023	98.80	gold quality
jejunal mucosa	UBERON:0000399	98.32	gold quality
adrenal tissue	UBERON:0018303	97.65	gold quality
upper leg skin	UBERON:0004262	97.52	gold quality
jejunum	UBERON:0002115	97.35	gold quality
penis	UBERON:0000989	97.30	gold quality
urethra	UBERON:0000057	97.03	gold quality
parotid gland	UBERON:0001831	96.86	gold quality
lower esophagus	UBERON:0013473	96.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.78	gold quality
buccal mucosa cell	CL:0002336	96.72	gold quality
skin of abdomen	UBERON:0001416	96.57	gold quality
mammalian vulva	UBERON:0000997	96.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.45	gold quality
saliva-secreting gland	UBERON:0001044	96.37	gold quality
oral cavity	UBERON:0000167	96.34	gold quality
mucosa of stomach	UBERON:0001199	96.24	gold quality
minor salivary gland	UBERON:0001830	96.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.17	gold quality
cauda epididymis	UBERON:0004360	96.15	gold quality
skin of leg	UBERON:0001511	96.12	gold quality
pharyngeal mucosa	UBERON:0000355	95.84	gold quality
mammary duct	UBERON:0001765	95.69	gold quality
lower esophagus mucosa	UBERON:0035834	95.63	gold quality
esophagus	UBERON:0001043	95.57	gold quality
mouth mucosa	UBERON:0003729	95.51	gold quality
left ovary	UBERON:0002119	95.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.15	gold quality
zone of skin	UBERON:0000014	95.12	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	18.21
E-ANND-3	yes	11.50
E-MTAB-6142	no	155.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

241 targeting ATL2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• A family of human GTPases, atlastin-2 and -3 that are closely related to atlastin-1 are described. (PMID:18270207)
• The role of GTP hydrolysis in the ATL2 fusion mechanism also needs to be tempered by the uncertainty of whether the behavior of the ATL2 soluble domain, observed herein, reflects the behavior of the full-length, membrane-anchored protein. (PMID:22065636)
• These results suggest that the three ATLs have different capacities to mediate endoplasmic reticulum fusion, with ATL1 being the strongest and ATL3 being the weakest. (PMID:25773277)
• Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy. (PMID:33988678)
• Reconstitution of human atlastin fusion activity reveals autoinhibition by the C terminus. (PMID:34817557)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atl2	ENSDARG00000057719
mus_musculus	Atl2	ENSMUSG00000059811
rattus_norvegicus	Atl2	ENSRNOG00000006523
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Atlastin-2 — Q8NHH9 (reviewed: Q8NHH9)

Alternative names: ADP-ribosylation factor-like protein 6-interacting protein 2

All UniProt accessions (8): Q8NHH9, B5MCN0, C9JC25, C9JQQ5, F8WBH0, F8WD17, F8WEN4, H7C3A2

UniProt curated annotations — full annotation on UniProt →

Function. Atlastin-2 (ATL2) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It facilitates the formation of three-way junctions where ER tubules intersect. Two atlastin-2 on neighboring ER tubules bind GTP and form loose homodimers through the GB1/RHD3-type G domains and 3HB regions. Upon GTP hydrolysis, the 3HB regions tighten, pulling the membranes together to drive their fusion. After fusion, the homodimer disassembles upon release of inorganic phosphate (Pi). Subsequently, GDP dissociates, resetting the monomers to a conformation ready for a new fusion cycle.

Subunit / interactions. Monomeric and homodimeric. The homodimer, transiently formed by two molecules on opposing membranes, is the active form mediating ER membrane fusion. Interacts with REEP5 and RTN3; these proteins are involved in endoplasmic reticulum tubular network organization. Interacts with ZFYVE27; both proteins are involved in endoplasmic reticulum tubular network organization.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in peripheral tissues (at protein level).

Activity regulation. With its alternative C-terminus disrupting the autoinhibitory domain, this brain-specific isoform is probably more active at fusing ER membranes.

Domain organisation. The GB1/RHD3-type G domain mediates GTP-binding and hydrolysis as well as homodimerization. The two three-helix bundle (3HB) regions in the homodimer are loosely associated initially, but they tighten upon GTP hydrolysis, facilitating the fusion of membranes. The C-terminal autoinhibitory domain negatively regulates the GTPase-dependent fusogenic activity without affecting GTP-binding.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NHH9-1	1, AT2b	yes
Q8NHH9-2	2, AT2a
Q8NHH9-3	3
Q8NHH9-4	4
Q8NHH9-5	5

RefSeq proteins (10): NP_001129145, NP_001295005, NP_001317387, NP_001317388, NP_001317389, NP_001317390, NP_001317391, NP_001317392, NP_001317393, NP_071769 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003191	Guanylate-bd/ATL_C	Domain
IPR015894	Guanylate-bd_N	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030386	G_GB1_RHD3_dom	Domain
IPR036543	Guanylate-bd_C_sf	Homologous_superfamily

Pfam: PF02263, PF02841

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (59 total): binding site 21, mutagenesis site 15, region of interest 5, splice variant 4, topological domain 3, sequence variant 3, transmembrane region 2, modified residue 2, chain 1, coiled-coil region 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHH9-F1	84.36	0.54

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 (21): 104; 104; 105; 105; 106; 106; 107; 107; 108; 108; 108; 109 …

Post-translational modifications (2): 24, 270

Mutagenesis-validated functional residues (15):

Position	Phenotype
107	alters endoplasmic reticulum morphology.
244	alters endoplasmic reticulum morphogenesis.
372	no effect on gtp-binding or gtpase activity. loss of function in endoplasmic reticulum tubular network membrane organiza
380	loss of function in endoplasmic reticulum tubular network membrane organization.
380	no effect on gtp-binding or gtpase activity. loss of function in endoplasmic reticulum tubular network membrane organiza
384	loss of function in endoplasmic reticulum tubular network membrane organization.
431	no effect on function in endoplasmic reticulum tubular network membrane organization.
435	loss of function in endoplasmic reticulum tubular network membrane organization.
440	decreased function in endoplasmic reticulum tubular network membrane organization.
444	no effect on function in endoplasmic reticulum tubular network membrane organization.
447	no effect on function in endoplasmic reticulum tubular network membrane organization.
454	loss of function in endoplasmic reticulum tubular network membrane organization.
555	increased gtpase-dependent fusogenic activity.
556	increased gtpase-dependent fusogenic activity.
559	increased gtpase-dependent fusogenic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 272 (showing top): ATF_B, GOBP_MEMBRANE_FUSION, GOBP_VESICLE_MEDIATED_TRANSPORT, GGAMTNNNNNTCCY_UNKNOWN, WEI_MYCN_TARGETS_WITH_E_BOX, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, UEDA_PERIFERAL_CLOCK, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, ATF1_Q6, GOBP_ORGANELLE_MEMBRANE_FUSION, AAAGACA_MIR511, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, CREB_Q2_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AACTTT_UNKNOWN

GO Biological Process (5): endoplasmic reticulum organization (GO:0007029), endoplasmic reticulum membrane fusion (GO:0016320), protein homooligomerization (GO:0051260), endoplasmic reticulum tubular network membrane organization (GO:1990809), Golgi organization (GO:0007030)

GO Molecular Function (7): GTPase activity (GO:0003924), GTP binding (GO:0005525), metal ion binding (GO:0046872), GTPase-dependent fusogenic activity (GO:0140523), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum tubular network membrane (GO:0098826), endoplasmic reticulum subcompartment (GO:0098827)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	2
endomembrane system organization	2
endoplasmic reticulum membrane organization	2
endoplasmic reticulum organization	1
organelle membrane fusion	1
protein complex oligomerization	1
endoplasmic reticulum tubular network organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
GTPase activity	1
membrane fusion	1
fusogenic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
endoplasmic reticulum membrane	1
endoplasmic reticulum tubular network	1
endoplasmic reticulum	1
organelle subcompartment	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATL2	SPAST	Q9UBP0	970
ATL2	REEP1	Q9H902	949
ATL2	SPART	Q8N0X7	861
ATL2	RTN1	Q16799	857
ATL2	SSNA1	O43805	828
ATL2	REEP5	Q00765	819
ATL2	CHMP1B	Q7LBR1	752
ATL2	ARL6IP1	Q15041	701
ATL2	RTN2	O75298	671
ATL2	RTN3	O95197	651
ATL2	CKAP4	Q07065	621
ATL2	SPG7	Q9UQ90	607
ATL2	CNTLN	Q9NXG0	596
ATL2	REEP2	Q9BRK0	573
ATL2	LNPK	Q9C0E8	571

IntAct

75 interactions, top by confidence:

A	B	Type	Score
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
Copa	COPE	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	ATL2	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	REEP5	psi-mi:“MI:0914”(association)	0.540
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
ZFYVE27	ATL2	psi-mi:“MI:0915”(physical association)	0.500
ATL2	Rtn3	psi-mi:“MI:0915”(physical association)	0.400
Reep5	ATL2	psi-mi:“MI:0915”(physical association)	0.400
ATL2	Reep5	psi-mi:“MI:0915”(physical association)	0.400
SLC7A13	ATL2	psi-mi:“MI:0915”(physical association)	0.400
ATL3	SNX14	psi-mi:“MI:0914”(association)	0.350
ATL2	ACRBP	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
NCAPD3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
ARL6IP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATL2	ATL3	psi-mi:“MI:0914”(association)	0.350
ATL3	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPE	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (142): ATL2 (Affinity Capture-MS), ATL2 (Affinity Capture-MS), ATL2 (Affinity Capture-MS), ADD1 (Affinity Capture-MS), CSNK1G2 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), NELFA (Affinity Capture-MS), BCL7B (Affinity Capture-MS), RPP38 (Affinity Capture-MS), SNRNP27 (Affinity Capture-MS), FAM120A (Affinity Capture-MS), NNT (Affinity Capture-MS), KLHDC2 (Affinity Capture-MS), ATL3 (Affinity Capture-MS), STK39 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IMY7, A0JPA0, A2AP18, A8DYE2, J9SQF3, O00329, O35904, O75038, P0C1Q3, P0C588, P19687, P33402, P48736, P97557, Q02108, Q09M05, Q148L1, Q1LWG4, Q2TV84, Q2WEA5, Q3USB7, Q4ZHS0, Q502J0, Q5EBA1, Q60565, Q62688, Q69ZF7, Q6P4Q7, Q6PA06, Q7L5N7, Q7TN37, Q7Z2W7, Q7Z4N2, Q80YD1, Q8BTI9, Q8BYI6, Q8BZN2, Q8CIR4, Q8NHH9, Q8R455

Diamond homologs: O70418, Q0ZHH6, Q58D72, Q5R4P1, Q60HD2, Q6DD88, Q6GN29, Q6PA06, Q6PST4, Q8BH66, Q8NHH9, Q8WXF7, Q91YH5, Q95LN3, Q96DY5, Q9ULX5, Q9VC57, Q08DF2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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
COPI-dependent Golgi-to-ER retrograde traffic	7	13.4×	3e-04
Disorders of transmembrane transporters	5	12.0×	3e-03
COPI-mediated anterograde transport	6	11.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
intra-Golgi vesicle-mediated transport	6	36.7×	7e-06
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	6	23.5×	6e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	6	9.5×	4e-03
G protein-coupled receptor signaling pathway	12	5.1×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	88
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2422363	NC_000002.11:g.(?38297865)(38917056_?)del	Pathogenic

SpliceAI

2670 predictions. Top by Δscore:

Variant	Effect	Δscore
2:38296478:A:AC	donor_gain	1.0000
2:38296479:C:CC	donor_gain	1.0000
2:38296494:T:TA	donor_gain	1.0000
2:38298571:CATAC:C	acceptor_gain	1.0000
2:38298574:ACC:A	acceptor_loss	1.0000
2:38298576:C:CA	acceptor_loss	1.0000
2:38298577:T:A	acceptor_loss	1.0000
2:38299251:CAAA:C	donor_loss	1.0000
2:38299253:AACC:A	donor_loss	1.0000
2:38299254:A:T	donor_loss	1.0000
2:38299255:C:A	donor_loss	1.0000
2:38299265:A:AC	donor_gain	1.0000
2:38299266:C:CC	donor_gain	1.0000
2:38299323:GTTGC:G	acceptor_gain	1.0000
2:38299324:TTGC:T	acceptor_gain	1.0000
2:38299325:TGC:T	acceptor_gain	1.0000
2:38299326:GC:G	acceptor_gain	1.0000
2:38299327:CC:C	acceptor_gain	1.0000
2:38299328:C:CA	acceptor_loss	1.0000
2:38299328:C:CC	acceptor_gain	1.0000
2:38309377:A:C	donor_loss	1.0000
2:38309378:CC:C	donor_loss	1.0000
2:38309425:ATCT:A	donor_gain	1.0000
2:38309426:T:C	donor_gain	1.0000
2:38309502:AATAT:A	acceptor_gain	1.0000
2:38309503:ATAT:A	acceptor_gain	1.0000
2:38309504:TAT:T	acceptor_gain	1.0000
2:38309504:TATC:T	acceptor_loss	1.0000
2:38309505:AT:A	acceptor_gain	1.0000
2:38309505:ATC:A	acceptor_loss	1.0000

AlphaMissense

3860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:38298433:A:G	L448P	1.000
2:38298472:A:G	M435T	1.000
2:38299300:C:G	A386P	1.000
2:38299305:A:G	L384P	1.000
2:38299314:G:T	A381D	1.000
2:38299315:C:G	A381P	1.000
2:38299320:G:T	A379D	1.000
2:38299321:C:G	A379P	1.000
2:38299327:C:G	A377P	1.000
2:38300276:A:G	L375P	1.000
2:38300279:A:T	M374K	1.000
2:38309395:A:G	L352P	1.000
2:38309479:A:G	L324P	1.000
2:38309490:A:C	F320L	1.000
2:38309490:A:T	F320L	1.000
2:38309492:A:G	F320L	1.000
2:38310320:C:A	G311V	1.000
2:38310320:C:T	G311E	1.000
2:38310321:C:A	G311W	1.000
2:38310321:C:G	G311R	1.000
2:38310321:C:T	G311R	1.000
2:38310325:A:C	F309L	1.000
2:38310325:A:T	F309L	1.000
2:38310327:A:G	F309L	1.000
2:38310353:C:T	G300D	1.000
2:38310354:C:G	G300R	1.000
2:38310388:G:C	F288L	1.000
2:38310388:G:T	F288L	1.000
2:38310390:A:G	F288L	1.000
2:38310409:C:A	R281S	1.000

dbSNP variants (sampled 300 via entrez): RS1000027343 (2:38356501 C>T), RS1000060736 (2:38353407 T>A,C), RS1000063604 (2:38352669 T>C), RS1000078218 (2:38320692 C>A,T), RS1000108459 (2:38319543 G>C), RS1000145576 (2:38364361 A>T), RS1000150264 (2:38336994 G>C), RS1000160982 (2:38348720 T>A,C), RS1000189251 (2:38318687 T>C), RS1000226576 (2:38377726 C>CT), RS1000228296 (2:38333461 A>C,G), RS1000234221 (2:38348940 C>A,T), RS1000255447 (2:38337736 C>T), RS1000267446 (2:38306170 T>C), RS1000285156 (2:38328899 C>G,T)

Disease associations

OMIM: gene MIM:609368 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (2): congenital glaucoma (MONDO:0020366), Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006871	Hydrophthalmos	C11.250.480; C11.525.381.407.480; C16.131.384.480; C16.614.438
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: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs59569490	ATL2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, decreases reaction, increases abundance	4
sodium arsenite	increases abundance, increases expression, decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
GSK-J4	increases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression, increases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
K 7174	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	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Irinotecan	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Asbestos	affects expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1

Clinical trials (associated diseases)

206 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