STXBP6

Summary

STXBP6 (syntaxin binding protein 6, HGNC:19666) is a protein-coding gene on chromosome 14q12, encoding Syntaxin-binding protein 6 (Q8NFX7). Forms non-fusogenic complexes with SNAP25 and STX1A and may thereby modulate the formation of functional SNARE complexes and exocytosis.

Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in negative regulation of exocytosis. Located in adherens junction.

Source: NCBI Gene 29091 — RefSeq curated summary.

At a glance

• GWAS associations: 57
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001394410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19666
Approved symbol	STXBP6
Name	syntaxin binding protein 6
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	amisyn, HSPC156
Ensembl gene	ENSG00000168952
Ensembl biotype	protein_coding
OMIM	607958
Entrez	29091

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 40 protein_coding, 1 nonsense_mediated_decay

ENST00000323944, ENST00000396700, ENST00000419632, ENST00000546511, ENST00000548182, ENST00000548369, ENST00000550887, ENST00000886564, ENST00000886565, ENST00000886566, ENST00000886567, ENST00000886568, ENST00000886569, ENST00000886570, ENST00000886571, ENST00000886572, ENST00000886573, ENST00000886574, ENST00000886575, ENST00000886576, ENST00000886577, ENST00000886578, ENST00000886579, ENST00000886580, ENST00000886581, ENST00000886582, ENST00000886583, ENST00000886584, ENST00000886585, ENST00000886586, ENST00000886587, ENST00000886588, ENST00000925306, ENST00000925307, ENST00000949484, ENST00000949485, ENST00000949486, ENST00000949487, ENST00000949488, ENST00000949489, ENST00000949490

RefSeq mRNA: 18 — MANE Select: NM_001394410 NM_001304476, NM_001304477, NM_001351940, NM_001351941, NM_001351942, NM_001351943, NM_001394410, NM_001394411, NM_001394412, NM_001394413, NM_001394414, NM_001394415, NM_001394416, NM_001394417, NM_001394418, NM_001394419, NM_001394420, NM_014178

CCDS: CCDS9634

Canonical transcript exons

ENST00000323944 — 6 exons

Exon	Start	End
ENSE00001265629	24974665	24974850
ENSE00001373617	24809454	24812732
ENSE00002411040	25049878	25050147
ENSE00003528644	24819037	24819194
ENSE00003587726	24857027	24857157
ENSE00003601629	24855936	24856101

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9768 / max 127.1163, expressed in 1049 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142657	4.0421	890
142658	3.5133	814
142654	0.2901	105
142653	0.1313	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.46	gold quality
endothelial cell	CL:0000115	97.52	gold quality
lateral globus pallidus	UBERON:0002476	95.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.55	gold quality
corpus epididymis	UBERON:0004359	94.05	gold quality
body of pancreas	UBERON:0001150	93.66	gold quality
postcentral gyrus	UBERON:0002581	93.63	gold quality
superior vestibular nucleus	UBERON:0007227	93.40	gold quality
parietal lobe	UBERON:0001872	93.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.11	gold quality
superior frontal gyrus	UBERON:0002661	92.47	gold quality
right lung	UBERON:0002167	92.42	gold quality
subthalamic nucleus	UBERON:0001906	92.39	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.68	gold quality
oocyte	CL:0000023	91.38	gold quality
secondary oocyte	CL:0000655	91.24	gold quality
primary visual cortex	UBERON:0002436	91.00	gold quality
caudate nucleus	UBERON:0001873	90.90	gold quality
inferior vagus X ganglion	UBERON:0005363	90.46	gold quality
substantia nigra pars compacta	UBERON:0001965	90.37	gold quality
pancreas	UBERON:0001264	90.34	gold quality
occipital lobe	UBERON:0002021	90.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.00	gold quality
pons	UBERON:0000988	89.83	gold quality
prefrontal cortex	UBERON:0000451	89.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.28	gold quality
ventral tegmental area	UBERON:0002691	89.24	gold quality
entorhinal cortex	UBERON:0002728	88.93	gold quality
anterior cingulate cortex	UBERON:0009835	88.92	gold quality
cingulate cortex	UBERON:0003027	88.77	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	59.48
E-MTAB-10287	yes	49.23
E-MTAB-8142	yes	18.53
E-ANND-3	yes	11.35
E-MTAB-10283	no	408.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

142 targeting STXBP6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
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-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 4)

• Data suggest that genetic variations within CD6 and syntaxin binding protein 6 (STXBP6) may influence response to TNFalpha inhibitors in patients with rheumatoid arthritis (RA). (PMID:22685579)
• Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients. (PMID:28198450)
• Identification of STXBP6-IRF1 positive feedback loop in regulation of PD-L1 in cancer. (PMID:32700091)
• A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression. (PMID:39227839)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stxbp6l	ENSDARG00000028354
danio_rerio	stxbp6	ENSDARG00000088862
mus_musculus	Stxbp6	ENSMUSG00000046314
rattus_norvegicus	Stxbp6	ENSRNOG00000004198
drosophila_melanogaster	Sec3	FBGN0266669
caenorhabditis_elegans		WBGENE00018703

Paralogs (2): EXOC1 (ENSG00000090989), EXOC1L (ENSG00000250821)

Protein

Protein identifiers

Syntaxin-binding protein 6 — Q8NFX7 (reviewed: Q8NFX7)

Alternative names: Amisyn

All UniProt accessions (2): Q8NFX7, F8VZZ2

UniProt curated annotations — full annotation on UniProt →

Function. Forms non-fusogenic complexes with SNAP25 and STX1A and may thereby modulate the formation of functional SNARE complexes and exocytosis.

Subunit / interactions. Part of a ternary complex containing SNAP25 and STX1A that can be dissociated by NAPA and NSF. Interacts with STX4A.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Detected at low levels in brain, and at very low levels in heart, adrenal gland, testis, liver and kidney.

Miscellaneous. May be due to an intron retention. May be due to an intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NFX7-1	1	yes
Q8NFX7-2	2
Q8NFX7-3	3

RefSeq proteins (18): NP_001291405, NP_001291406, NP_001338869, NP_001338870, NP_001338871, NP_001338872, NP_001381339, NP_001381340, NP_001381341, NP_001381342, NP_001381343, NP_001381344, NP_001381345, NP_001381346, NP_001381347, NP_001381348, NP_001381349, NP_054897 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028258	Sec3-PIP2_bind	Domain
IPR037821	STXBP6_PH	Domain
IPR037822	STXBP6_SNARE	Domain
IPR042855	V_SNARE_CC	Domain

Pfam: PF00957, PF15277

UniProt features (9 total): splice variant 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFX7-F1	87.31	0.66

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_VESICLE_ORGANIZATION, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, chr14q12, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, PATIL_LIVER_CANCER, GOBP_CELL_CELL_ADHESION, GOBP_EXOCYTOSIS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (4): SNARE complex assembly (GO:0035493), regulation of SNARE complex assembly (GO:0035542), negative regulation of exocytosis (GO:0045920), cell-cell adhesion (GO:0098609)

GO Molecular Function (1): cadherin binding involved in cell-cell adhesion (GO:0098641)

GO Cellular Component (3): cytoplasm (GO:0005737), adherens junction (GO:0005912), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
vesicle fusion	1
protein-containing complex assembly	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
exocytosis	1
regulation of exocytosis	1
negative regulation of secretion by cell	1
cell adhesion	1
cadherin binding	1
cell-cell adhesion	1
cell-cell adhesion mediator activity	1
intracellular anatomical structure	1
cell-cell junction	1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STXBP6	STXBP5	Q5T5C0	943
STXBP6	STX4	Q12846	857
STXBP6	SLC22A17	Q8WUG5	845
STXBP6	COCH	O43405	825
STXBP6	VAMP8	Q9BV40	762
STXBP6	SNAP25	P13795	698
STXBP6	CBLN3	Q6UW01	524
STXBP6	SDR39U1	Q9NRG7	513
STXBP6	NYNRIN	Q9P2P1	509
STXBP6	GZMB	P10144	505
STXBP6	RNF17	Q9BXT8	491
STXBP6	PTER	Q96BW5	452
STXBP6	STOML1	Q9UBI4	447
STXBP6	REC114	Q7Z4M0	426
STXBP6	ENTPD4	Q9Y227	425

IntAct

12 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX3	NBAS	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
BMP2K	STXBP6	psi-mi:“MI:0915”(physical association)	0.370
STXBP6	SNAP23	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (36): STXBP6 (Proximity Label-MS), ALS2 (Affinity Capture-MS), STX7 (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX3 (Affinity Capture-MS), STX4 (Affinity Capture-MS), NAPG (Affinity Capture-MS), STX8 (Affinity Capture-MS), VTI1B (Affinity Capture-MS), STX12 (Affinity Capture-MS), ATG7 (Affinity Capture-MS), STX6 (Affinity Capture-MS), NAPA (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), STXBP6 (Proximity Label-MS)

ESM2 similar proteins: A0A2R8RWN9, A0JN27, E2R222, F1LTR1, O94925, P13264, P22234, P51583, P61201, P61202, P61203, P97834, Q07G17, Q13042, Q13888, Q15303, Q15645, Q28D01, Q2TBV1, Q2TBV5, Q2YDL1, Q3MHJ2, Q4R9A8, Q4VC33, Q5F398, Q5JUK3, Q5R532, Q5RB59, Q5RBN9, Q5RKJ1, Q5SP67, Q5TDH0, Q5XHZ9, Q61527, Q6GR10, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7SXR3

Diamond homologs: Q2YDL1, Q8NFX7, Q8R3S6, Q8R3T5, Q9NV70, Q5DQR4, Q5SQE2, Q5T5C0, Q8K400, Q9WU70, Q9Y2K9, A0A1B0GW35, B9EK06, Q20678, Q9VVG4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4443 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24819031:GCCCA:G	donor_loss	1.0000
14:24819032:CCCA:C	donor_loss	1.0000
14:24819033:CCA:C	donor_loss	1.0000
14:24819034:CA:C	donor_loss	1.0000
14:24819035:A:AT	donor_loss	1.0000
14:24819036:CCTTG:C	donor_loss	1.0000
14:24819192:TTC:T	acceptor_gain	1.0000
14:24819193:TCC:T	acceptor_loss	1.0000
14:24819195:C:CC	acceptor_gain	1.0000
14:24855934:ACCTC:A	donor_gain	1.0000
14:24855935:CCTCC:C	donor_gain	1.0000
14:24856102:CTGGA:C	acceptor_loss	1.0000
14:24856103:T:C	acceptor_loss	1.0000
14:24857023:T:TA	donor_loss	1.0000
14:24857025:ACC:A	donor_gain	1.0000
14:24857026:C:CT	donor_loss	1.0000
14:24857026:CCC:C	donor_gain	1.0000
14:24857153:TGTCA:T	acceptor_gain	1.0000
14:24857156:CA:C	acceptor_gain	1.0000
14:24857157:AC:A	acceptor_loss	1.0000
14:24857158:C:A	acceptor_loss	1.0000
14:24857158:C:CC	acceptor_gain	1.0000
14:24857159:T:G	acceptor_loss	1.0000
14:24857162:C:CT	acceptor_gain	1.0000
14:24857163:A:T	acceptor_gain	1.0000
14:24899964:C:T	acceptor_gain	1.0000
14:24974851:C:CC	acceptor_gain	1.0000
14:24974852:T:C	acceptor_gain	1.0000
14:24974854:T:C	acceptor_gain	1.0000
14:24974854:T:TC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000652 (14:24913212 A>G), RS1000017727 (14:25004530 A>C), RS1000020753 (14:25024452 A>C), RS1000021041 (14:24933427 T>C), RS1000035093 (14:24938998 A>G), RS1000066801 (14:24991669 G>A,C), RS1000073122 (14:24877336 T>C), RS1000124149 (14:24820028 C>T), RS1000143446 (14:24833325 C>T), RS1000150705 (14:24915953 T>A,C), RS1000152915 (14:25046186 A>G), RS1000173281 (14:25040004 T>C), RS1000180419 (14:24979462 G>A), RS1000181399 (14:24897726 T>C), RS1000201157 (14:25031058 G>A,C)

Disease associations

OMIM: gene MIM:607958 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST000890_3	Hippocampal volume	1.000000e-06
GCST001134_5	White blood cell types	1.000000e-08
GCST001521_22	Subcutaneous adipose tissue	6.000000e-06
GCST002570_1	Overweight status	6.000000e-07
GCST002783_391	Body mass index	1.000000e-11
GCST002783_477	Body mass index	1.000000e-11
GCST002783_77	Body mass index	5.000000e-11
GCST002934_24	Zinc levels	9.000000e-06
GCST003075_47	Cognitive decline rate in late mild cognitive impairment	2.000000e-07
GCST003075_51	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST004065_14	Waist circumference	2.000000e-09
GCST004065_55	Waist circumference	1.000000e-07
GCST004066_121	Hip circumference	5.000000e-09
GCST004066_46	Hip circumference	1.000000e-06
GCST004557_23	Body mass index	3.000000e-08
GCST004557_235	Body mass index	4.000000e-08
GCST004558_155	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004558_20	Body mass index (joint analysis main effects and physical activity interaction)	4.000000e-07
GCST004559_17	Body mass index in physically active individuals	6.000000e-07
GCST004559_99	Body mass index in physically active individuals	9.000000e-07
GCST004606_77	Eosinophil count	2.000000e-09
GCST004610_137	White blood cell count	3.000000e-24
GCST004613_37	Sum neutrophil eosinophil counts	5.000000e-24
GCST004614_15	Granulocyte count	1.000000e-23
GCST004620_85	Sum basophil neutrophil counts	1.000000e-21
GCST004624_152	Sum eosinophil basophil counts	4.000000e-10
GCST004625_144	Monocyte count	2.000000e-35
GCST004626_126	Myeloid white cell count	6.000000e-27
GCST004629_135	Neutrophil count	6.000000e-22
GCST004632_39	Lymphocyte percentage of white cells	3.000000e-12

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0005091	monocyte count
EFO:0005935	overweight body mass index status
EFO:0004340	body mass index
EFO:0007710	cognitive decline measurement
EFO:0008002	physical activity measurement
EFO:0004842	eosinophil count
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007017	peanut allergy measurement
EFO:0006798	neuritic plaque measurement
EFO:0004747	protein measurement
EFO:0010731	response to low calorie diet
EFO:0007986	reticulocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Temozolomide	decreases expression, affects response to substance	2
Arsenic Trioxide	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, decreases reaction	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
nickel sulfate	decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases 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
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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