STXBP5

Summary

STXBP5 (syntaxin binding protein 5, HGNC:19665) is a protein-coding gene on chromosome 6q24.3, encoding Syntaxin-binding protein 5 (Q5T5C0). Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release.

Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 134957 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 172 total
• MANE Select transcript: NM_001127715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19665
Approved symbol	STXBP5
Name	syntaxin binding protein 5
Location	6q24.3
Locus type	gene with protein product
Status	Approved
Aliases	tomosyn, LLGL3, tomosyn-1
Ensembl gene	ENSG00000164506
Ensembl biotype	protein_coding
OMIM	604586
Entrez	134957

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 12 retained_intron, 7 protein_coding, 5 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000321680, ENST00000367475, ENST00000367480, ENST00000367481, ENST00000392291, ENST00000443556, ENST00000546097, ENST00000706848, ENST00000706849, ENST00000706850, ENST00000706851, ENST00000706852, ENST00000706853, ENST00000706854, ENST00000706855, ENST00000706856, ENST00000706857, ENST00000706858, ENST00000706859, ENST00000706860, ENST00000706861, ENST00000706862, ENST00000706863, ENST00000706864, ENST00000706865, ENST00000706866, ENST00000927180, ENST00000927181, ENST00000964473

RefSeq mRNA: 3 — MANE Select: NM_001127715 NM_001127715, NM_001394409, NM_139244

CCDS: CCDS47499, CCDS5211

Canonical transcript exons

ENST00000321680 — 28 exons

Exon	Start	End
ENSE00001223363	147339337	147339384
ENSE00001223369	147339179	147339238
ENSE00001223375	147334157	147334222
ENSE00001223459	147353323	147353373
ENSE00002440308	147364001	147364166
ENSE00002449959	147205971	147206068
ENSE00002463389	147313884	147314031
ENSE00002463895	147327125	147327276
ENSE00002466376	147314596	147314636
ENSE00002486430	147324959	147325084
ENSE00002499052	147315515	147315735
ENSE00002501967	147373731	147373842
ENSE00002509317	147311455	147311527
ENSE00002521496	147316229	147316407
ENSE00002533053	147382778	147382998
ENSE00002534239	147314264	147314331
ENSE00002718028	147363335	147363704
ENSE00003476804	147239170	147239270
ENSE00003498745	147278081	147278204
ENSE00003501051	147235250	147235331
ENSE00003514805	147267084	147267167
ENSE00003565639	147260615	147260749
ENSE00003566305	147262290	147262353
ENSE00003607153	147291094	147291172
ENSE00003615567	147310084	147310238
ENSE00003783954	147359084	147359323
ENSE00003997246	147204417	147204682
ENSE00003997247	147384714	147390473

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 95.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7488 / max 2632.8414, expressed in 1811 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70380	16.5812	1782
70383	3.7406	1297
70390	1.4992	198
70388	1.1293	135
70382	1.0956	546
70381	1.0874	531
70384	0.9563	465
70386	0.8747	160
70385	0.4150	146
70379	0.1912	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.21	gold quality
calcaneal tendon	UBERON:0003701	93.00	gold quality
cerebellar hemisphere	UBERON:0002245	92.79	gold quality
cerebellar cortex	UBERON:0002129	92.69	gold quality
endothelial cell	CL:0000115	92.60	gold quality
cerebellum	UBERON:0002037	92.32	gold quality
sperm	CL:0000019	92.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.87	gold quality
superior frontal gyrus	UBERON:0002661	91.86	gold quality
primary visual cortex	UBERON:0002436	91.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.16	gold quality
islet of Langerhans	UBERON:0000006	90.82	gold quality
middle temporal gyrus	UBERON:0002771	90.79	gold quality
postcentral gyrus	UBERON:0002581	90.75	gold quality
anterior cingulate cortex	UBERON:0009835	90.67	gold quality
prefrontal cortex	UBERON:0000451	90.21	gold quality
neocortex	UBERON:0001950	89.90	gold quality
frontal cortex	UBERON:0001870	89.89	gold quality
parietal lobe	UBERON:0001872	89.81	gold quality
cerebral cortex	UBERON:0000956	89.52	gold quality
occipital lobe	UBERON:0002021	89.47	gold quality
right frontal lobe	UBERON:0002810	89.04	gold quality
cortical plate	UBERON:0005343	88.29	gold quality
entorhinal cortex	UBERON:0002728	88.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.55	gold quality
bone marrow cell	CL:0002092	87.49	gold quality
brain	UBERON:0000955	87.30	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	573.40
E-MTAB-9067	yes	12.43
E-CURD-112	yes	10.27
E-MTAB-9801	yes	8.47
E-ANND-3	yes	6.96
E-GEOD-137537	yes	5.71
E-MTAB-7303	no	83.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

429 targeting STXBP5, 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-5011-5P	100.00	83.46	5820
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-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-8485	100.00	77.57	4731
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-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 19)

• Characterization of a related rat gene (PMID:10066450)
• Genetic variability in STXBP5 and STX2 affects both VWF concentration and activity in young individuals with premature arterial thrombosis. (PMID:21156930)
• Genetic variation in STXBP5 gene is associated with venous thrombosis. (PMID:21163921)
• multiple domains outside the R-SNARE of tomosyn are critical to the efficacy of inhibition by tomosyn on exocytotic secretion (PMID:21330375)
• Genetic variation in STXBP5 is associated with bleeding phenotype in female type 1 von Willebrand Disease patients. (PMID:22792389)
• Identify 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. (PMID:24578379)
• STXBP5 is required for normal arterial hemostasis, due to its contributions to platelet granule cargo packaging and secretion (PMID:25244094)
• STXBP5 inhibits endothelial exocytosis and promotes platelet secretion (PMID:25244095)
• Genetic variations in STXBP5 and CLEC4M are associated with VWF level variation in type 1, but not in type 2 von Willebrand disease. (PMID:25832887)
• Using CRISPR/Cas9 genome editing, identified a human nonsynonymous SNP rs1039084 in the STXBP5 locus as a causal variant for a decreased thrombotic phenotype. (PMID:28062498)
• Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca(2+)-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca(2+)-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca(2+) influx. (PMID:28325894)
• Assisted by NSF/alpha-SNAP, syntaxin-1 escapes tomosyn arrest and assembles into the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes the transit of syntaxin-1 from the Munc18-1/syntaxin-1 complex to the SNARE complex (PMID:29485200)
• Findings identified tomosyn-1 as an inhibitor of mast cell degranulation that required PKCdelta to switch its interaction with STX partners during fusion. (PMID:29970602)
• A haplotype containing the STXBP5 Asn436Ser (rs1039084) mutation is associated with type 1 von Willebrand disease in a Swedish population. (PMID:29972863)
• Interaction networks of Weibel-Palade body regulators syntaxin-3 and syntaxin binding protein 5 in endothelial cells. (PMID:31201948)
• STXBP5-AS1 might function as a ceRNA to drive CC cells proliferation and invasion via regulating miR-96-5p/PTEN axis. (PMID:31212131)
• Genetic evidence for an inhibitory role of tomosyn in insulin-stimulated GLUT4 exocytosis. (PMID:32851733)
• Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma. (PMID:33965377)
• Characterization of a related rat protein (PMID:9620695)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stxbp5a	ENSDARG00000002656
danio_rerio	stxbp5b	ENSDARG00000029234
mus_musculus	Stxbp5	ENSMUSG00000019790
rattus_norvegicus	Stxbp5	ENSRNOG00000013351
drosophila_melanogaster	Tomosyn	FBGN0030412
caenorhabditis_elegans	tom-1	WBGENE00006594

Paralogs (3): LLGL2 (ENSG00000073350), LLGL1 (ENSG00000131899), STXBP5L (ENSG00000145087)

Protein

Protein identifiers

Syntaxin-binding protein 5 — Q5T5C0 (reviewed: Q5T5C0)

Alternative names: Lethal(2) giant larvae protein homolog 3, Tomosyn-1

All UniProt accessions (5): A0A9L9PXY2, A0A9L9PY07, Q5T5C0, F6VFW0, H0Y332

UniProt curated annotations — full annotation on UniProt →

Function. Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding.

Subunit / interactions. Interacts with STX1A and STX1B via its v-SNARE homology domain. Part of a complex that contains STX1, STXBP5, SNAP25 and SYT1. Part of a complex that contains STXBP5, STX4A and SNAP23.

Subcellular location. Cytoplasm. Cell membrane. Cytoplasmic vesicle membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle. Synapse.

Similarity. Belongs to the WD repeat L(2)GL family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5T5C0-1	1	yes
Q5T5C0-2	2
Q5T5C0-3	3

RefSeq proteins (3): NP_001121187, NP_001381338, NP_640337 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000664	Lethal2_giant	Family
IPR001680	WD40_rpt	Repeat
IPR013577	LLGL2	Domain
IPR013905	Lgl_C_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR042855	V_SNARE_CC	Domain

Pfam: PF00400, PF08366, PF08596

UniProt features (38 total): repeat 14, modified residue 12, region of interest 4, compositionally biased region 3, splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T5C0-F1	78.93	0.57

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 (12): 692, 723, 759, 762, 782, 784, 785, 900, 902, 1039, 1058, 1131

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 335 (showing top): GOCC_SECRETORY_GRANULE, AAGTCCA_MIR422B_MIR422A, TTTGTAG_MIR520D, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GROSS_HYPOXIA_VIA_ELK3_UP, GOBP_POSITIVE_REGULATION_OF_EXOCYTOSIS, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN

GO Biological Process (7): exocytosis (GO:0006887), Golgi to plasma membrane transport (GO:0006893), regulation of synaptic vesicle priming (GO:0010807), protein transport (GO:0015031), regulation of exocytosis (GO:0017157), positive regulation of exocytosis (GO:0045921), regulation of synaptic vesicle exocytosis (GO:2000300)

GO Molecular Function (5): GTPase activator activity (GO:0005096), syntaxin-1 binding (GO:0017075), syntaxin binding (GO:0019905), myosin II binding (GO:0045159), protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), synaptic vesicle (GO:0008021), SNARE complex (GO:0031201), extrinsic component of neuronal dense core vesicle membrane (GO:0098674), hippocampal mossy fiber to CA3 synapse (GO:0098686), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
exocytosis	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
synaptic vesicle priming	1
regulation of protein-containing complex assembly	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
syntaxin binding	1
SNARE binding	1
myosin binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
monoatomic ion channel complex	1
plasma membrane signaling receptor complex	1
exocytic vesicle	1
presynapse	1
membrane protein complex	1
extrinsic component of dense core granule membrane	1
neuronal dense core vesicle membrane	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1

Protein interactions and networks

STRING

986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STXBP5	SNAP25	P13795	975
STXBP5	STXBP6	Q8NFX7	943
STXBP5	STX1A	Q16623	938
STXBP5	SYBU	Q9NX95	873
STXBP5	STX4	Q12846	835
STXBP5	SNAP23	O00161	826
STXBP5	NAPA	P54920	789
STXBP5	VAMP8	Q9BV40	788
STXBP5	VAMP2	P19065	782
STXBP5	STX1B	P61266	777
STXBP5	RAB3A	P20336	770
STXBP5	STXBP1	P61764	751
STXBP5	SYN1	P17600	727
STXBP5	SYN2	Q92777	727
STXBP5	SYN3	O14994	718

IntAct

39 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
STX19	STXBP1	psi-mi:“MI:0914”(association)	0.850
STX3	SNAP23	psi-mi:“MI:0914”(association)	0.660
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
STX3	YKT6	psi-mi:“MI:0914”(association)	0.530
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
STX12	FAM234B	psi-mi:“MI:0914”(association)	0.530
STX3	NBAS	psi-mi:“MI:0914”(association)	0.530
STXBP5	RUVBL1	psi-mi:“MI:0915”(physical association)	0.400
ARRB1		psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
VTI1B	NBAS	psi-mi:“MI:0914”(association)	0.350
STX6	NBAS	psi-mi:“MI:0914”(association)	0.350
STX12	NBAS	psi-mi:“MI:0914”(association)	0.350
STX7	TYW5	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
STX19	SNAP23	psi-mi:“MI:0914”(association)	0.350
STX8	GOSR2	psi-mi:“MI:0914”(association)	0.350
SNAP29	RNF40	psi-mi:“MI:0914”(association)	0.350
NAPG	NBAS	psi-mi:“MI:0914”(association)	0.350
SCGN	CNOT1	psi-mi:“MI:0914”(association)	0.350
SNAP29	SNAP23	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS), STXBP5 (Affinity Capture-MS)

ESM2 similar proteins: A1L3L9, A2X2K3, A5D7H2, B6VA23, F1QH17, P36876, P36877, P50410, P54614, P56932, P58405, P63150, P63151, P97888, Q00005, Q00006, Q0D2F4, Q0E2P1, Q13033, Q29090, Q38821, Q39247, Q4R7Z4, Q4R8L3, Q5E9Q7, Q5NVK4, Q5R4A2, Q5T5C0, Q5Z8Z7, Q5ZHN3, Q5ZIY5, Q66LE6, Q6AY57, Q6DIY3, Q6NY64, Q6P1F6, Q6QEF8, Q6ZWR4, Q7ZWU5, Q7ZX64

Diamond homologs: B8AP31, O13923, O14021, O22466, O22467, O22468, O22469, O89053, O93377, O94244, P0CS36, P0CS37, P39984, P49178, P90916, P90917, Q09028, Q10G81, Q16576, Q24572, Q2UA71, Q3MHL3, Q3SWX8, Q40687, Q4I7L0, Q4P553, Q4R304, Q4WEI5, Q54ED4, Q54SD4, Q59RH5, Q5M7K4, Q5R654, Q5RF92, Q5T5C0, Q60972, Q60973, Q61Y48, Q6C7Q4, Q6CSI1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
Intra-Golgi traffic	6	59.9×	9e-08
Intra-Golgi and retrograde Golgi-to-ER traffic	5	20.1×	3e-04
Membrane Trafficking	7	10.0×	3e-04
Vesicle-mediated transport	7	9.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	7	144.9×	6e-12
membrane fusion	6	101.2×	2e-09
vesicle fusion	6	97.6×	2e-09
intracellular protein transport	12	21.0×	2e-11
exocytosis	5	20.5×	1e-04
protein stabilization	6	10.8×	4e-04
protein transport	7	8.3×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	22
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

5407 predictions. Top by Δscore:

Variant	Effect	Δscore
6:147237527:GAAA:G	donor_gain	1.0000
6:147239168:A:G	acceptor_gain	1.0000
6:147239267:AAAGG:A	donor_loss	1.0000
6:147239268:AAGGT:A	donor_loss	1.0000
6:147239269:AGG:A	donor_loss	1.0000
6:147239270:GGT:G	donor_loss	1.0000
6:147239271:G:GC	donor_loss	1.0000
6:147239272:T:A	donor_loss	1.0000
6:147260745:GAACT:G	donor_gain	1.0000
6:147260750:G:GG	donor_gain	1.0000
6:147267080:ACAGC:A	acceptor_loss	1.0000
6:147267081:CAGCT:C	acceptor_loss	1.0000
6:147267082:A:AG	acceptor_gain	1.0000
6:147267083:G:GC	acceptor_gain	1.0000
6:147267083:GC:G	acceptor_gain	1.0000
6:147267163:ATGAG:A	donor_loss	1.0000
6:147267164:TGAG:T	donor_loss	1.0000
6:147267165:GAGGT:G	donor_loss	1.0000
6:147267166:AGGT:A	donor_loss	1.0000
6:147267167:GGTA:G	donor_loss	1.0000
6:147267168:GT:G	donor_loss	1.0000
6:147267169:T:A	donor_loss	1.0000
6:147278075:CTATA:C	acceptor_loss	1.0000
6:147278076:TATA:T	acceptor_loss	1.0000
6:147278078:TA:T	acceptor_loss	1.0000
6:147278079:A:AG	acceptor_gain	1.0000
6:147278080:G:GG	acceptor_gain	1.0000
6:147278080:GGCT:G	acceptor_gain	1.0000
6:147278202:ATGG:A	donor_loss	1.0000
6:147278203:TGGT:T	donor_loss	1.0000

AlphaMissense

7479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:147239177:T:C	L113P	1.000
6:147239182:A:C	S115R	1.000
6:147239184:T:A	S115R	1.000
6:147239184:T:G	S115R	1.000
6:147239212:T:A	W125R	1.000
6:147239212:T:C	W125R	1.000
6:147239252:T:C	L138P	1.000
6:147260649:T:A	W156R	1.000
6:147260649:T:C	W156R	1.000
6:147260653:T:C	L157P	1.000
6:147260661:G:C	G160R	1.000
6:147260662:G:A	G160D	1.000
6:147260673:G:C	G164R	1.000
6:147260674:G:A	G164D	1.000
6:147260674:G:T	G164V	1.000
6:147260689:T:A	V169D	1.000
6:147260730:T:A	W183R	1.000
6:147260730:T:C	W183R	1.000
6:147260732:G:C	W183C	1.000
6:147260732:G:T	W183C	1.000
6:147267120:T:A	W223R	1.000
6:147267120:T:C	W223R	1.000
6:147278099:T:A	W245R	1.000
6:147278099:T:C	W245R	1.000
6:147278129:A:C	S255R	1.000
6:147278131:T:A	S255R	1.000
6:147278131:T:G	S255R	1.000
6:147278142:G:A	G259D	1.000
6:147310179:T:C	L338P	1.000
6:147313934:T:A	V399D	1.000

dbSNP variants (sampled 300 via entrez): RS1000000394 (6:147228889 A>G), RS1000012574 (6:147331416 T>G), RS1000023110 (6:147287505 A>G), RS1000049361 (6:147240578 C>G), RS1000050196 (6:147312559 G>C,T), RS1000050753 (6:147270417 T>A), RS1000054485 (6:147366081 G>A), RS1000083917 (6:147281575 A>G), RS1000088003 (6:147386432 T>C), RS1000106031 (6:147300041 C>T), RS1000120983 (6:147372775 G>A), RS1000121436 (6:147355615 C>T), RS1000131013 (6:147276207 T>C), RS1000176507 (6:147210577 G>A), RS1000205506 (6:147234771 C>T)

Disease associations

OMIM: gene MIM:604586 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000627_1	vWF levels	1.000000e-22
GCST002104_15	Bronchopulmonary dysplasia	5.000000e-06
GCST002104_16	Bronchopulmonary dysplasia	1.000000e-06
GCST002374_2	Plasma plasminogen activator levels	3.000000e-14
GCST003210_3	Low vWF levels	6.000000e-10
GCST004029_42	Angiotensin-converting enzyme inhibitor intolerance	9.000000e-06
GCST006628_60	Systolic blood pressure	6.000000e-11
GCST007445_29	Factor VIII levels	3.000000e-13
GCST007445_39	Factor VIII levels	2.000000e-15
GCST007445_40	Factor VIII levels	1.000000e-15
GCST007445_66	Factor VIII levels	2.000000e-14
GCST007445_9	Factor VIII levels	4.000000e-13
GCST007446_11	vWF levels	6.000000e-38
GCST007446_68	vWF levels	6.000000e-42
GCST009030_7	Venous thromboembolism	5.000000e-09
GCST012489_117	Heel bone mineral density x serum urate levels interaction	3.000000e-10
GCST90002389_140	Lymphocyte percentage of white cells	6.000000e-13
GCST90002395_491	Mean platelet volume	1.000000e-10
GCST90002398_413	Neutrophil count	1.000000e-15
GCST90002399_162	Neutrophil percentage of white cells	5.000000e-10
GCST90002407_531	White blood cell count	1.000000e-13

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0006335	systolic blood pressure
EFO:0004630	factor VIII measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder