STX1B

Summary

STX1B (syntaxin 1B, HGNC:18539) is a protein-coding gene on chromosome 16p11.2, encoding Syntaxin-1B (P61266). Potentially involved in docking of synaptic vesicles at presynaptic active zones.

The protein encoded by this gene belongs to a family of proteins thought to play a role in the exocytosis of synaptic vesicles. Vesicle exocytosis releases vesicular contents and is important to various cellular functions. For instance, the secretion of transmitters from neurons plays an important role in synaptic transmission. After exocytosis, the membrane and proteins from the vesicle are retrieved from the plasma membrane through the process of endocytosis. Mutations in this gene have been identified as one cause of fever-associated epilepsy syndromes. A possible link between this gene and Parkinson’s disease has also been suggested.

Source: NCBI Gene 112755 — RefSeq curated summary.

At a glance

• Gene–disease (curated): generalized epilepsy with febrile seizures plus (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 17
• Clinical variants (ClinVar): 440 total — 33 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 35
• MANE Select transcript: NM_052874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18539
Approved symbol	STX1B
Name	syntaxin 1B
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099365
Ensembl biotype	protein_coding
OMIM	601485
Entrez	112755

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000215095, ENST00000565419, ENST00000566211, ENST00000916717

RefSeq mRNA: 1 — MANE Select: NM_052874 NM_052874

CCDS: CCDS10699

Canonical transcript exons

ENST00000215095 — 10 exons

Exon	Start	End
ENSE00000648538	31000928	31001002
ENSE00000648539	30997502	30997575
ENSE00000648540	30996951	30997059
ENSE00000648541	30996683	30996756
ENSE00001234884	30989256	30992901
ENSE00001781346	30993130	30993240
ENSE00001794523	30993347	30993484
ENSE00002590988	31010367	31010638
ENSE00003586497	31001529	31001603
ENSE00003644879	31001094	31001193

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 98.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0913 / max 1751.1409, expressed in 1298 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157113	12.4172	631
157108	1.4288	701
157114	0.4109	79
157107	0.2424	114
157109	0.1474	60
157115	0.1034	60
157112	0.0927	45
157111	0.0922	37
157105	0.0757	32
157106	0.0621	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.22	gold quality
cerebellar hemisphere	UBERON:0002245	97.95	gold quality
cerebellar cortex	UBERON:0002129	97.87	gold quality
right frontal lobe	UBERON:0002810	96.86	gold quality
cerebellum	UBERON:0002037	96.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.23	gold quality
prefrontal cortex	UBERON:0000451	95.19	gold quality
anterior cingulate cortex	UBERON:0009835	94.85	gold quality
postcentral gyrus	UBERON:0002581	94.62	gold quality
frontal cortex	UBERON:0001870	94.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.06	gold quality
neocortex	UBERON:0001950	93.96	gold quality
superior frontal gyrus	UBERON:0002661	93.67	gold quality
cerebral cortex	UBERON:0000956	92.24	gold quality
parietal lobe	UBERON:0001872	92.10	gold quality
nucleus accumbens	UBERON:0001882	91.96	gold quality
hypothalamus	UBERON:0001898	91.69	gold quality
amygdala	UBERON:0001876	91.05	gold quality
cortical plate	UBERON:0005343	91.05	gold quality
putamen	UBERON:0001874	90.62	gold quality
caudate nucleus	UBERON:0001873	90.31	gold quality
entorhinal cortex	UBERON:0002728	90.18	gold quality
brain	UBERON:0000955	89.76	gold quality
temporal lobe	UBERON:0001871	89.69	gold quality
forebrain	UBERON:0001890	89.37	gold quality
Ammon’s horn	UBERON:0001954	89.22	gold quality
primary visual cortex	UBERON:0002436	88.69	gold quality
occipital lobe	UBERON:0002021	85.56	gold quality
substantia nigra	UBERON:0002038	84.75	gold quality
midbrain	UBERON:0001891	83.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.06

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
STXBP1	Unknown

miRNA regulators (miRDB)

139 targeting STX1B, 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-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4306	99.72	70.50	3630

Literature-anchored findings (GeneRIF, showing 14)

• The STX1B-Delta transmembrane domain is characterized as the first nucleoplasmic syntaxin with no transmembrane domain. (PMID:18691641)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Data indicate that single nucleotide polymorphism (SNPS) in the 3’-untranslated region of the fucosyltransferase 1 (FUT1) gene and intron of the syntaxin 1B (STX1B) gene were the top hits for Kawasaki disease (KD) susceptibility. (PMID:25101798)
• STX1B and the presynaptic release machinery may have a role in fever-associated epilepsy syndromes (PMID:25362483)
• The data of this study suggested that the STX1B polymorphisms are associated with Parkinson disease etiology. (PMID:25534083)
• Findings suggested that STX1B rs4889603, FAM47E rs6812193 and SCARB2 rs6825004 do not confer a significant risk for Parkinson’s disease (PMID:26224037)
• 529 adults (n = 325 European-Americans, 204 Egyptians) on a stable warfarin dose were genotyped for GGCX rs12714145 and rs10654848, FPGS rs7856096, and STX1B rs4889606. (PMID:26751406)
• genetic variations in STX1B, DNMT3A and CYP1A1 have roles in influencing warfarin maintenance dose (PMID:27740732)
• Strong deregulation of SNAP25 and STX1B has been found at both mRNA and protein levels suggesting impaired synaptic function through SNAP25 reduction as a possible cause of calcium elevation and glutamate excitotoxicity in amyotrophic lateral sclerosis. (PMID:28855684)
• Transcranial magnetic stimulation measures of motor cortex excitability show normal excitability in adult STX1B mutation carriers with a history of seizures. (PMID:29101845)
• that a sleep-related hypermotor epilepsy phenotype can be associated with syntaxin-1B gene mutation (PMID:30378543)
• These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies. More often, loss-of-function mutations were found in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes. (PMID:30737342)
• Delineation of epileptic and neurodevelopmental phenotypes associated with variants in STX1B. (PMID:33677401)
• Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features. (PMID:34764822)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stx1b	ENSDARG00000000503
mus_musculus	Stx1b	ENSMUSG00000030806
rattus_norvegicus	Stx1b	ENSRNOG00000019193
drosophila_melanogaster	Syx1A	FBGN0013343
caenorhabditis_elegans		WBGENE00006798

Paralogs (12): STX7 (ENSG00000079950), STX4 (ENSG00000103496), STX1A (ENSG00000106089), STX2 (ENSG00000111450), STX12 (ENSG00000117758), STX16 (ENSG00000124222), STX11 (ENSG00000135604), STX17 (ENSG00000136874), STX5 (ENSG00000162236), STX3 (ENSG00000166900), TSNARE1 (ENSG00000171045), STX19 (ENSG00000178750)

Protein

Protein identifiers

Syntaxin-1B — P61266 (reviewed: P61266)

Alternative names: Syntaxin-1B1, Syntaxin-1B2

All UniProt accessions (1): P61266

UniProt curated annotations — full annotation on UniProt →

Function. Potentially involved in docking of synaptic vesicles at presynaptic active zones. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm.

Subunit / interactions. Interacts with OTOF. Interacts with SYT6 and SYT8; the interaction is Ca(2+)-dependent.

Subcellular location. Membrane Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Post-translational modifications. Phosphorylated by CK2.

Disease relevance. Generalized epilepsy with febrile seizures plus 9 (GEFSP9) [MIM:616172] An autosomal dominant neurologic disorder characterized by febrile and/or afebrile seizures manifesting in early childhood. Seizure are variable and include generalized tonic-clonic, atonic, myoclonic, complex partial, and absence types. Most patients have remission of seizures later in childhood with no residual neurologic deficits. Rarely, patients may show mild developmental delay or mild intellectual disabilities. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The glycine-rich C-terminus serves as an unconventional nuclear localization signal.

Similarity. Belongs to the syntaxin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61266-1	1	yes
P61266-2	2, STX1B-DeltaTMD

RefSeq proteins (1): NP_443106* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR006011	Syntaxin_N	Domain
IPR006012	Syntaxin/epimorphin_CS	Conserved_site
IPR010989	SNARE	Homologous_superfamily
IPR045242	Syntaxin	Family

Pfam: PF00804, PF05739

UniProt features (20 total): sequence conflict 8, sequence variant 2, modified residue 2, chain 1, topological domain 1, transmembrane region 1, domain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61266-F1	84.17	0.49

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 (2): 10, 14

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5250971	Toxicity of botulinum toxin type C (botC)
R-HSA-5682910	LGI-ADAM interactions
R-HSA-1266738	Developmental Biology
R-HSA-1643685	Disease
R-HSA-168799	Neurotoxicity of clostridium toxins
R-HSA-5339562	Uptake and actions of bacterial toxins
R-HSA-5663205	Infectious disease
R-HSA-9824439	Bacterial Infection Pathways

MSigDB gene sets: 251 (showing top): GOBP_PINOCYTOSIS, PAX4_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (20): positive regulation of neurotransmitter secretion (GO:0001956), intracellular protein transport (GO:0006886), exocytosis (GO:0006887), obsolete vesicle docking involved in exocytosis (GO:0006904), regulation of gene expression (GO:0010468), regulation of synaptic vesicle priming (GO:0010807), negative regulation of neuron projection development (GO:0010977), obsolete synaptic vesicle docking (GO:0016081), synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), obsolete vesicle docking (GO:0048278), calcium ion-regulated exocytosis of neurotransmitter (GO:0048791), regulation of synaptic activity (GO:0060025), spontaneous neurotransmitter secretion (GO:0061669), negative regulation of synaptic vesicle recycling (GO:1903422), positive regulation of spontaneous neurotransmitter secretion (GO:1904050), negative regulation of macropinocytosis (GO:1905302), positive regulation of excitatory postsynaptic potential (GO:2000463), neurotransmitter transport (GO:0006836), synaptic vesicle exocytosis (GO:0016079), vesicle-mediated transport (GO:0016192)

GO Molecular Function (5): SNARE binding (GO:0000149), signaling receptor binding (GO:0005102), SNAP receptor activity (GO:0005484), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), axon (GO:0030424), SNARE complex (GO:0031201), neuromuscular junction (GO:0031594), presynaptic active zone membrane (GO:0048787), cytoskeleton (GO:0005856), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Neurotoxicity of clostridium toxins	1
Developmental Biology	1
Uptake and actions of bacterial toxins	1
Bacterial Infection Pathways	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
neurotransmitter secretion	3
vesicle fusion to plasma membrane	2
synaptic vesicle exocytosis	2
transport	2
protein binding	2
intracellular membraneless organelle	2
cytoplasm	2
synapse	2
regulation of neurotransmitter secretion	1
positive regulation of synaptic transmission	1
positive regulation of neurotransmitter transport	1
positive regulation of secretion by cell	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
vesicle-mediated transport	1
secretion by cell	1
gene expression	1
regulation of macromolecule biosynthetic process	1
synaptic vesicle priming	1
regulation of protein-containing complex assembly	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
synaptic vesicle membrane organization	1
calcium-ion regulated exocytosis	1
regulation of synapse structure or activity	1
modulation of chemical synaptic transmission	1
spontaneous synaptic transmission	1
synaptic vesicle recycling	1
negative regulation of transport	1
regulation of synaptic vesicle recycling	1
positive regulation of neurotransmitter secretion	1
spontaneous neurotransmitter secretion	1
regulation of spontaneous neurotransmitter secretion	1
macropinocytosis	1
negative regulation of pinocytosis	1
regulation of macropinocytosis	1
positive regulation of signal transduction	1

Protein interactions and networks

STRING

1979 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STX1B	SNAP25	P13795	980
STX1B	VAMP2	P19065	963
STX1B	VAMP3	Q15836	961
STX1B	STXBP1	P61764	940
STX1B	VAMP8	Q9BV40	886
STX1B	SNAP23	O00161	879
STX1B	SYT1	P21579	848
STX1B	VAMP7	P51809	843
STX1B	VAMP1	P23763	833
STX1B	STX6	O43752	831
STX1B	UNC13B	O14795	796
STX1B	STXBP5	Q5T5C0	777
STX1B	STXBP3	O00186	695
STX1B	UNC13A	Q9UPW8	690
STX1B	SYN1	P17600	668

IntAct

95 interactions, top by confidence:

A	B	Type	Score
STX1B	VAMP2	psi-mi:“MI:0915”(physical association)	0.660
STX1B	FBXO28	psi-mi:“MI:0915”(physical association)	0.660
STX1B	VAMP2	psi-mi:“MI:2364”(proximity)	0.660
FBXO28	STX1B	psi-mi:“MI:2364”(proximity)	0.660
STX1B	KCNN4	psi-mi:“MI:0915”(physical association)	0.560
STX1B	FGA	psi-mi:“MI:0915”(physical association)	0.560
STX1B	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
STX1B	NAPB	psi-mi:“MI:0915”(physical association)	0.560
TXLNA	STX1B	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX1B	STX4	psi-mi:“MI:0915”(physical association)	0.560
SNAP29	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX2	STX1B	psi-mi:“MI:0915”(physical association)	0.560
VAMP1	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX1B	ACBD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX1B	FAM81A	psi-mi:“MI:0915”(physical association)	0.560
STX1B	AQP6	psi-mi:“MI:0915”(physical association)	0.560
KCNN4	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX1B	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
GJA8	STX1B	psi-mi:“MI:0915”(physical association)	0.560
STX1B	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
STX1B	MMGT1	psi-mi:“MI:0915”(physical association)	0.560
STX1B	GPR152	psi-mi:“MI:0915”(physical association)	0.560
STX1B	EBP	psi-mi:“MI:0915”(physical association)	0.560
STX1B	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
BET1	STX1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (56): STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Affinity Capture-MS), STX1B (Two-hybrid), SNAP23 (Reconstituted Complex), VAPB (Reconstituted Complex), STX1B (Two-hybrid), STX1B (Two-hybrid)

ESM2 similar proteins: A8WVD0, O15400, O16000, O35526, O70257, O70439, P32850, P32851, P32856, P32867, P39926, P50279, P61264, P61265, P61266, P61267, P61268, P70452, Q00262, Q08849, Q08850, Q0VCI2, Q12846, Q13277, Q16623, Q16932, Q20024, Q24547, Q3SWZ3, Q3ZBT5, Q42374, Q59YF0, Q5R4L2, Q5R602, Q5TX47, Q64704, Q7XIE2, Q8N4C7, Q8R1Q0, Q8VZU2

Diamond homologs: A8WVD0, O16000, O35526, O75558, P32850, P32851, P32854, P32856, P50279, P61264, P61265, P61266, P61267, P61268, P70452, P91409, Q00262, Q08849, Q08850, Q12846, Q13277, Q16623, Q16932, Q20797, Q24547, Q3SWZ3, Q5R4L2, Q5TX47, Q64704, Q6F3B4, Q8R1Q0, Q9D3G5, G3V7P1, O14662, O15400, O64791, O65359, O70257, O70439, O94651

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Membrane Trafficking	6	9.3×	7e-04
Vesicle-mediated transport	6	8.7×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle priming	5	93.3×	2e-07
exocytosis	8	28.2×	6e-08
intracellular protein transport	6	9.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	33
Uncertain significance	164
Likely benign	164
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066204	NM_052874.5(STX1B):c.537+2T>C	Pathogenic
1070577	NM_052874.5(STX1B):c.334del (p.Leu112fs)	Pathogenic
1308652	NM_052874.5(STX1B):c.160A>T (p.Lys54Ter)	Pathogenic
1326264	NM_052874.5(STX1B):c.286G>T (p.Glu96Ter)	Pathogenic
1451994	NM_052874.5(STX1B):c.205_205+1del	Pathogenic
1481736	NM_052874.5(STX1B):c.430T>C (p.Cys144Arg)	Pathogenic
162395	NM_052874.5(STX1B):c.166C>T (p.Gln56Ter)	Pathogenic
162397	NM_052874.5(STX1B):c.140C>A (p.Ser47Ter)	Pathogenic
162398	NM_052874.5(STX1B):c.647T>A (p.Val216Glu)	Pathogenic
162399	NM_052874.5(STX1B):c.676G>C (p.Gly226Arg)	Pathogenic
2576582	NM_052874.5(STX1B):c.354+1G>C	Pathogenic
2693031	NM_052874.5(STX1B):c.786+1G>A	Pathogenic
2748620	NM_052874.5(STX1B):c.815del (p.Val272fs)	Pathogenic
280465	NM_052874.5(STX1B):c.58del (p.Val20fs)	Pathogenic
2811860	NM_052874.5(STX1B):c.786+1G>T	Pathogenic
2813188	NM_052874.5(STX1B):c.39del (p.Asp13fs)	Pathogenic
2849088	NM_052874.5(STX1B):c.338_354+15del	Pathogenic
2864828	NM_052874.5(STX1B):c.366del (p.Ser123fs)	Pathogenic
3384007	NM_052874.5(STX1B):c.451C>T (p.Gln151Ter)	Pathogenic
3650187	NM_052874.5(STX1B):c.565C>T (p.Gln189Ter)	Pathogenic
3663941	NM_052874.5(STX1B):c.2T>A (p.Met1Lys)	Pathogenic
4726056	NM_052874.5(STX1B):c.725dup (p.Tyr242Ter)	Pathogenic
4732781	NM_052874.5(STX1B):c.846dup (p.Gly283fs)	Pathogenic
4735231	NM_052874.5(STX1B):c.613G>T (p.Glu205Ter)	Pathogenic
567167	NM_052874.5(STX1B):c.35_36dup (p.Asp13fs)	Pathogenic
590057	NM_052874.5(STX1B):c.733C>T (p.Arg245Ter)	Pathogenic
657728	NM_052874.5(STX1B):c.404del (p.Ala135fs)	Pathogenic
661190	NC_000016.10:g.(?31000908)(31001623_?)del	Pathogenic
807504	NM_052874.5(STX1B):c.165dup (p.Gln56fs)	Pathogenic
813789	NM_052874.5(STX1B):c.382del (p.Glu128fs)	Pathogenic

SpliceAI

1533 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30993128:AC:A	donor_gain	1.0000
16:30993129:CC:C	donor_gain	1.0000
16:30993162:T:A	donor_gain	1.0000
16:30993236:TCTCC:T	acceptor_gain	1.0000
16:30993237:CTCC:C	acceptor_gain	1.0000
16:30993237:CTCCC:C	acceptor_gain	1.0000
16:30993238:TCC:T	acceptor_gain	1.0000
16:30993238:TCCCT:T	acceptor_gain	1.0000
16:30993239:CC:C	acceptor_gain	1.0000
16:30993239:CCC:C	acceptor_gain	1.0000
16:30993240:CC:C	acceptor_gain	1.0000
16:30993241:C:CC	acceptor_gain	1.0000
16:30993242:T:A	acceptor_loss	1.0000
16:30993248:C:CT	acceptor_gain	1.0000
16:30993341:CAGTA:C	donor_loss	1.0000
16:30993342:AGTAC:A	donor_loss	1.0000
16:30993343:GTAC:G	donor_loss	1.0000
16:30993344:TA:T	donor_loss	1.0000
16:30993345:ACCTG:A	donor_loss	1.0000
16:30993346:CCTGG:C	donor_gain	1.0000
16:30993384:T:C	donor_gain	1.0000
16:30993480:TTGAT:T	acceptor_gain	1.0000
16:30993481:TGAT:T	acceptor_gain	1.0000
16:30993482:GAT:G	acceptor_gain	1.0000
16:30993485:C:CC	acceptor_gain	1.0000
16:30993485:C:CG	acceptor_loss	1.0000
16:30993490:G:GC	acceptor_gain	1.0000
16:30996681:A:AC	donor_gain	1.0000
16:30996681:ACGT:A	donor_gain	1.0000
16:30996682:C:CC	donor_gain	1.0000

AlphaMissense

1926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30993159:C:G	A253P	1.000
16:30993180:C:G	A246P	1.000
16:30993367:C:G	A219P	1.000
16:30993377:A:C	F215L	1.000
16:30993377:A:T	F215L	1.000
16:30993379:A:G	F215L	1.000
16:30993390:A:G	L211P	1.000
16:30993411:A:G	L204P	1.000
16:30996959:A:G	L152P	1.000
16:30996965:C:G	R150P	1.000
16:30996992:C:G	R141P	1.000
16:30997512:C:G	R115P	1.000
16:30993179:G:T	A246D	0.999
16:30993201:A:G	S239P	0.999
16:30993221:A:C	I232S	0.999
16:30993221:A:T	I232N	0.999
16:30993224:C:G	R231P	0.999
16:30993240:C:G	G226R	0.999
16:30993240:C:T	G226R	0.999
16:30993360:A:G	L221P	0.999
16:30993369:A:C	M218R	0.999
16:30993378:A:C	F215C	0.999
16:30993429:T:G	H198P	0.999
16:30993432:C:A	R197M	0.999
16:30993450:A:G	L191P	0.999
16:30996692:G:C	F176L	0.999
16:30996692:G:T	F176L	0.999
16:30996693:A:G	F176S	0.999
16:30996694:A:G	F176L	0.999
16:30996729:A:G	L164P	0.999

dbSNP variants (sampled 300 via entrez): RS1000043816 (16:31010733 G>A,T), RS1000071183 (16:31004706 G>A), RS1000204614 (16:31012326 G>C), RS1000342093 (16:30991504 G>T), RS1000703481 (16:31005187 G>A), RS1000794680 (16:30991783 G>A), RS1000845243 (16:30999988 G>A), RS1000923688 (16:30999526 G>A), RS1001080874 (16:31006260 C>T), RS1001164785 (16:30991981 T>C), RS1001382529 (16:31010801 G>A), RS1001401083 (16:31006482 G>A), RS1001435006 (16:31011119 G>A,T), RS1001668098 (16:31003443 T>A), RS1001741762 (16:31003100 A>C)

Disease associations

OMIM: gene MIM:601485 | disease phenotypes: MIM:616172, MIM:604233

GenCC curated gene-disease

Disease	Classification	Inheritance
generalized epilepsy with febrile seizures plus, type 9	Strong	Autosomal dominant
generalized epilepsy with febrile seizures plus	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
generalized epilepsy with febrile seizures plus	Definitive	AD

Mondo (4): generalized epilepsy with febrile seizures plus, type 9 (MONDO:0014517), generalized epilepsy with febrile seizures plus (MONDO:0018214), neurodevelopmental disorder (MONDO:0700092), generalized epilepsy (MONDO:0100574)

Orphanet (1): Genetic epilepsy with febrile seizure plus (Orphanet:36387)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001337	Tremor
HP:0001763	Pes planus
HP:0002067	Bradykinesia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus
HP:0002197	Generalized-onset seizure
HP:0002311	Incoordination
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002384	Focal impaired awareness seizure
HP:0002539	Cortical dysplasia
HP:0003066	Limited knee extension
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004684	Talipes valgus
HP:0007010	Poor fine motor coordination
HP:0007058	Generalized cerebral atrophy/hypoplasia
HP:0007359	Focal-onset seizure
HP:0008770	Obsessive-compulsive trait
HP:0010819	Atonic seizure
HP:0010850	EEG with spike-wave complexes

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST002544_4	Parkinson’s disease	2.000000e-12
GCST002738_4	Psoriasis	3.000000e-07
GCST003791_9	Response to metformin (IC50)	9.000000e-06
GCST004066_128	Hip circumference	9.000000e-09
GCST004066_50	Hip circumference	3.000000e-06
GCST005276_4	Dementia with Lewy bodies	1.000000e-08
GCST007347_1	Juvenile myoclonic epilepsy	3.000000e-11
GCST009107_3	Body mass index variance	1.000000e-16
GCST009108_15	Waist circumference variance	1.000000e-11
GCST009109_15	Hip circumference variance	3.000000e-12
GCST009121_16	Body mass index	7.000000e-24
GCST009122_10	Waist circumference	6.000000e-22
GCST009123_13	Hip circumference	2.000000e-27
GCST010204_133	Low density lipoprotein cholesterol levels	8.000000e-11
GCST010988_43	Adult body size	5.000000e-24
GCST010991_46	Parkinson’s disease	1.000000e-08
GCST011122_23	Walking pace	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4889606	Efficacy	3	warfarin
rs72800847	Dosage	3	warfarin	Heart valve replacement

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4889606	STX1B	3	3.25	1	warfarin
rs72800847	STX1B	3	2.25	1	warfarin

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
dicrotophos	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
Acetaminophen	decreases expression	1
Carmustine	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Pesticides	affects methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Vanadates	increases expression	1
Gold Compounds	increases expression	1
Acrylamide	decreases expression	1
Magnetite Nanoparticles	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C1TD	HIHDNEi004-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice