STX1A

Summary

STX1A (syntaxin 1A, HGNC:11433) is a protein-coding gene on chromosome 7q11.23, encoding Syntaxin-1A (Q16623). Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis.

This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6804 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 53 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 212
• MANE Select transcript: NM_004603

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11433
Approved symbol	STX1A
Name	syntaxin 1A
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	HPC-1, p35-1
Ensembl gene	ENSG00000106089
Ensembl biotype	protein_coding
OMIM	186590
Entrez	6804

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 protein_coding, 5 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000222812, ENST00000395154, ENST00000395155, ENST00000395156, ENST00000461441, ENST00000462135, ENST00000470878, ENST00000480126, ENST00000484736, ENST00000491427, ENST00000491645, ENST00000494245, ENST00000496216, ENST00000497980, ENST00000910650, ENST00000929307, ENST00000971340

RefSeq mRNA: 2 — MANE Select: NM_004603 NM_001165903, NM_004603

CCDS: CCDS34655, CCDS55120

Canonical transcript exons

ENST00000222812 — 10 exons

Exon	Start	End
ENSE00001017403	73719602	73719669
ENSE00001666229	73700730	73700840
ENSE00003486867	73703755	73703828
ENSE00003488858	73704148	73704256
ENSE00003519598	73709045	73709122
ENSE00003577314	73705150	73705224
ENSE00003596585	73699210	73700484
ENSE00003597685	73704350	73704423
ENSE00003657220	73708589	73708688
ENSE00003676399	73702845	73702982

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2435 / max 391.9425, expressed in 1608 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84321	10.9091	1606
84322	0.2786	94
84320	0.0558	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.02	gold quality
prefrontal cortex	UBERON:0000451	97.73	gold quality
cerebellar hemisphere	UBERON:0002245	97.70	gold quality
cerebellar cortex	UBERON:0002129	97.59	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.38	gold quality
frontal pole	UBERON:0002795	97.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.00	gold quality
anterior cingulate cortex	UBERON:0009835	96.97	gold quality
cingulate cortex	UBERON:0003027	96.95	gold quality
frontal cortex	UBERON:0001870	96.40	gold quality
frontal lobe	UBERON:0016525	96.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.28	gold quality
cerebellum	UBERON:0002037	96.02	gold quality
neocortex	UBERON:0001950	95.94	gold quality
pituitary gland	UBERON:0000007	95.64	gold quality
islet of Langerhans	UBERON:0000006	95.47	gold quality
adenohypophysis	UBERON:0002196	95.29	gold quality
cortical plate	UBERON:0005343	94.93	gold quality
cerebral cortex	UBERON:0000956	94.32	gold quality
amygdala	UBERON:0001876	94.08	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.74	gold quality
temporal lobe	UBERON:0001871	91.61	gold quality
orbitofrontal cortex	UBERON:0004167	91.44	gold quality
superior frontal gyrus	UBERON:0002661	91.26	gold quality
gall bladder	UBERON:0002110	90.50	gold quality
telencephalon	UBERON:0001893	90.20	gold quality
forebrain	UBERON:0001890	89.78	gold quality
primary visual cortex	UBERON:0002436	89.76	gold quality
Ammon’s horn	UBERON:0001954	89.62	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	516.86
E-HCAD-25	yes	75.09
E-MTAB-5061	yes	14.79
E-MTAB-7303	no	580.31
E-ANND-3	no	2.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting STX1A, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-8064	99.45	66.92	875

Literature-anchored findings (GeneRIF, showing 40)

• SNAP-25 traffics to the plasma membrane by a syntaxin-independent mechanism. (PMID:12114505)
• Munc18b binds to syntaxins 1A, 2, and 3 and regulates vesicle transport to the apical plasma membrane (PMID:12198139)
• CFTR channels are coordinately regulated by two cognate t-SNAREs, SNAP-23 (synaptosome-associated protein of 23 kDa) and syntaxin 1A. (PMID:12209004)
• interacts with CFTR protein differently from interactions with SNARE. (PMID:12446681)
• Syntaxin/Munc18 interactions in the late events during vesicle fusion and release in exocytosis (PMID:15175344)
• interacts with dopamine transporter (PMID:15202772)
• A significant genetic association was found between schizophrenia and an intron 7 single nucleotide polymorphism (SNP) tested. Haplotype analysis supported the association with several significant values that appear to be driven by the intron 7 SNP. (PMID:15219469)
• cleavage of APP but not syntaxin 1 is independent of cell surface regulation by extracellular ligands (PMID:15316009)
• Syn-1A binds both NBFs of SUR1 and SUR2A but appears to exhibit distinct interactions with NBF2 of these SUR proteins in modulating the KATP channels in islet beta cells and cardiac myocytes (PMID:15339904)
• Syntaxin-1A actions on sulfonylurea receptor 2A blocks acidic pH-induced cardiac K(ATP) channel activation (PMID:16672225)
• Norepinephrine transpossrter/syntaxin 1A complex rapidly redistributes, upon amphetamine treatment, when mechanisms supported by the transporter’s NH2 terminus are eliminated. (PMID:17032905)
• analysis of the spatially distinct modes of munc18-syntaxin 1 interaction (PMID:17264080)
• the mechanisms involved in Syn1A-K(v) interactions vary significantly between K(v) channels, thus providing a wide scope for Syn1A modulation of exocytosis and membrane excitability (PMID:17506992)
• the H(abc) domain has a role in membrane trafficking and targeting of syntaxin 1A (PMID:17543282)
• A lower frequency of the PRM -352T allele of the STX1A gene in overweight/obese subjects impaires glucose regulation, particularly among individuals with combined glucose intolerance and overt diabetes. (PMID:17912268)
• We have identified a new three-gene classifier that is independent of and improves on stage to stratify early-stage NSCLC patients with significantly different prognoses. (PMID:18065728)
• The expression of the SNARE protein SNAP-25 and its cellular homologue SNAP-23, as well as syntaxin1 and VAMP (vesicle-associated membrane protein) in samples of normal parathyroid tissue, chief cell adenoma, and parathyroid carcinoma, was examined. (PMID:18457912)
• SNARE complex-related genes STX1A, VAMP2 and SNAP25 do not play a major role in susceptibility to schizophrenia in the Japanese population (PMID:18512733)
• STX1A might influence the serotonergic system during neurodevelopment (PMID:18593506)
• Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3. (PMID:19004828)
• Homology with vesicle fusion mediator syntaxin-1a predicts determinants of epimorphin/syntaxin-2 function in mammary epithelial morphogenesis.( (PMID:19129200)
• This analysis revealed significant differences in both allele frequencies and genotype distributions of the STX1A gene in migraine. (PMID:19368856)
• We confirmed the involvement of syntaxin 1A in migraine susceptibility regarding rs941298. In addition, we found rs6951030 to also be associated in Portuguese migraine patients. (PMID:20385907)
• syntaxin 1A, a neuronal regulator of presynaptic vesicle release, may play a role in WS and be a component of the cellular pathway determining human intelligence. (PMID:20422020)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer. (PMID:20564318)
• association of STX1A with autism in a trio association study; in the anterior cingulate gyrus region, STX1A expression in the autism group was found to be significantly lower than controls; suggests a possible role of STX1A in pathogenesis of autism (PMID:21118708)
• ATP regulates pancreatic beta-cell K(ATP) channel activity, not only by its direct actions on Kir6.2 pore subunit, but also via ATP modulation of Syn-1A binding to SUR1. (PMID:21173146)
• Exocytotic dysfunctions in schizophrenia are probably related to an imbalance of the interaction between munc18-1a and SNARE (mainly syntaxin-1A) complex. (PMID:21669024)
• Recombinant alpha-SNAP-M105I has greater affinity for the cytosolic portion of immunoprecipitated syntaxin than the wild type protein. (PMID:21789195)
• Forming an acceptor SNARE complex between syntaxin-1A and SNAP-25 weakens but does not abrogate cholesterol-controlled cluster formation and indicates that the reconstitution process results in equal incorporation of protein at either lipid composition. (PMID:21916482)
• Syntaxin 1A effects may be additive but can be blocked at different concentration ranges of calmodulin, suggesting selective presynaptic targeting to directly regulate exocytosis. (PMID:21976501)
• A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis. (PMID:22130660)
• Our results provide support for the hypothesis that STX1A represents a susceptibility gene for migraine (PMID:22250207)
• DrrA activation of the Rab1 GTPase on plasma membrane-derived organelles stimulated the tethering of endoplasmic reticulum-derived vesicles, resulting in vesicle fusion through the pairing of Sec22b with the plasma membrane syntaxin proteins. (PMID:22264512)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Nesca directly binds KIF5B, kinesin light-chain and syntaxin-1 (PMID:22404429)
• Direct interaction between syntaxin 1A and the Kv2.1 C-terminus is required for efficient insulin exocytosis and glucose-stimulated insulin secretion. (PMID:22411134)
• The histone modification marks were significantly increased in bipolar disorder and major depression and this effect was correlated with significant increases in Syn1a gene expression. (PMID:22571925)
• Platelets deficient in Munc18b from a Familial Hemophagocytic Lymphohistiocytosis type 5 had secretion defect. (PMID:22791290)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stx1a	ENSDARG00000058994
mus_musculus	Stx1a	ENSMUSG00000007207
rattus_norvegicus	Stx1a	ENSRNOG00000029165
drosophila_melanogaster	Syx1A	FBGN0013343
caenorhabditis_elegans		WBGENE00006798

Paralogs (12): STX7 (ENSG00000079950), STX1B (ENSG00000099365), STX4 (ENSG00000103496), STX2 (ENSG00000111450), STX12 (ENSG00000117758), STX16 (ENSG00000124222), STX11 (ENSG00000135604), STX17 (ENSG00000136874), STX5 (ENSG00000162236), STX3 (ENSG00000166900), TSNARE1 (ENSG00000171045), STX19 (ENSG00000178750)

Protein

Protein identifiers

Syntaxin-1A — Q16623 (reviewed: Q16623)

Alternative names: Neuron-specific antigen HPC-1

All UniProt accessions (4): Q16623, A0A0C4DFZ1, A8MZ54, Q75ME0

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis. Part of the SNARE (Soluble NSF Attachment Receptor) complex composed of SNAP25, STX1A and VAMP2 which mediates the fusion of synaptic vesicles with the presynaptic plasma membrane. STX1A and SNAP25 are localized on the plasma membrane while VAMP2 resides in synaptic vesicles. The pairing of the three SNAREs from the N-terminal SNARE motifs to the C-terminal anchors leads to the formation of the SNARE complex, which brings membranes into close proximity and results in final fusion. Participates in the calcium-dependent regulation of acrosomal exocytosis in sperm. Also plays an important role in the exocytosis of hormones such as insulin or glucagon-like peptide 1 (GLP-1).

Subunit / interactions. Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex constitutes the basic catalytic machinery of the complex neurotransmitter release apparatus. The SNARE complex interacts with CPLX1. Interacts with STXBP1. The interaction with STXBP1 promotes assembly of the SNARE complex. Interacts (via C-terminus) with KCNB1 (via C-terminus); the interaction increases in a calcium-dependent manner and induces a pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts with SYTL4. Interacts with STXBP6. Interacts with PLCL1 (via C2 domain). Interacts with OTOF. Interacts with LGI3. Interacts (via the H3 domain) with SLC6A4 (via the N-terminus); this interaction regulates SLC4A6 channel conductance in thalamocortical neurons. Interacts with SYT6 and SYT8; the interaction is Ca(2+)-dependent. Interacts with VAMP8. Interacts with SNAP23. Interacts with VAPA and SYBU. Interacts with PRRT2. Interacts with SEPT8. Interacts with STXBP5L. Interacts with synaptotagmin-1/SYT1. Interacts with SEPTIN5; in the cerebellar cortex. Interacts with SEPTIN4; in the striatum.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Synapse. Synaptosome. Cell membrane Secreted.

Tissue specificity. Highly expressed in embryonic spinal cord and ganglia and in adult cerebellum and cerebral cortex. Expressed in heart, liver, fat, skeletal muscle, kidney and brain.

Post-translational modifications. Phosphorylated by CK2. Phosphorylation at Ser-188 by DAPK1 significantly decreases its interaction with STXBP1. Sumoylated, sumoylation is required for regulation of synaptic vesicle endocytosis.

Disease relevance. STX1A is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Miscellaneous. Expression is up-regulated by phorbol 12-myristate 13-acetate (PMA), but not by forskolin.

Similarity. Belongs to the syntaxin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16623-1	1	yes
Q16623-2	2, 1C
Q16623-3	3

RefSeq proteins (2): NP_001159375, NP_004594* (*=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): modified residue 4, cross-link 3, mutagenesis site 3, topological domain 2, splice variant 2, sequence conflict 2, chain 1, transmembrane region 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16623-F1	84.94	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 (7): 252, 253, 256, 14, 64, 95, 188

Mutagenesis-validated functional residues (3):

Position	Phenotype
252	complete loss of sumoylation; when associated with r-253 and r-256.
253	complete loss of sumoylation; when associated with r-252 and r-256.
256	complete loss of sumoylation; when associated with r-252 and r-253.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-264876	Insulin processing
R-HSA-422356	Regulation of insulin secretion
R-HSA-449836	Other interleukin signaling
R-HSA-5250971	Toxicity of botulinum toxin type C (botC)
R-HSA-5682910	LGI-ADAM interactions
R-HSA-6794361	Neurexins and neuroligins
R-HSA-888590	GABA synthesis, release, reuptake and degradation
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-168799	Neurotoxicity of clostridium toxins
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-449147	Signaling by Interleukins
R-HSA-5339562	Uptake and actions of bacterial toxins
R-HSA-5663205	Infectious disease
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 860 (showing top): GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_92, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_INSULIN_SECRETION, MODULE_563, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (28): positive regulation of neurotransmitter secretion (GO:0001956), intracellular protein transport (GO:0006886), exocytosis (GO:0006887), vesicle fusion (GO:0006906), response to gravity (GO:0009629), positive regulation of norepinephrine secretion (GO:0010701), regulation of synaptic vesicle priming (GO:0010807), synaptic vesicle exocytosis (GO:0016079), obsolete synaptic vesicle docking (GO:0016081), protein sumoylation (GO:0016925), calcium-ion regulated exocytosis (GO:0017156), insulin secretion (GO:0030073), secretion by cell (GO:0032940), positive regulation of catecholamine secretion (GO:0033605), SNARE complex assembly (GO:0035493), positive regulation of calcium ion-dependent exocytosis (GO:0045956), obsolete vesicle docking (GO:0048278), synaptic vesicle endocytosis (GO:0048488), regulation of insulin secretion (GO:0050796), protein localization to membrane (GO:0072657), positive regulation of excitatory postsynaptic potential (GO:2000463), neurotransmitter transport (GO:0006836), vesicle-mediated transport (GO:0016192), regulation of exocytosis (GO:0017157), regulated exocytosis (GO:0045055), positive regulation of exocytosis (GO:0045921), hormone secretion (GO:0046879), modulation of excitatory postsynaptic potential (GO:0098815)

GO Molecular Function (14): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), calcium channel inhibitor activity (GO:0019855), chloride channel inhibitor activity (GO:0019869), kinase binding (GO:0019900), myosin head/neck binding (GO:0032028), identical protein binding (GO:0042802), ATP-dependent protein binding (GO:0043008), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), myosin binding (GO:0017022), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (25): extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), endomembrane system (GO:0012505), secretory granule (GO:0030141), axon (GO:0030424), synaptic vesicle membrane (GO:0030672), SNARE complex (GO:0031201), nuclear membrane (GO:0031965), actomyosin (GO:0042641), neuron projection (GO:0043005), presynaptic active zone membrane (GO:0048787), synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex (GO:0070032), synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex (GO:0070033), synaptobrevin 2-SNAP-25-syntaxin-1a complex (GO:0070044), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), synaptic vesicle (GO:0008021), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), presynaptic membrane (GO:0042734), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Neurotransmitter release cycle	6
Peptide hormone metabolism	1
Integration of energy metabolism	1
Signaling by Interleukins	1
Neurotoxicity of clostridium toxins	1
Developmental Biology	1
Protein-protein interactions at synapses	1
Protein localization	1
Sensory processing of sound	1
Transmission across Chemical Synapses	1
Neuronal System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	6
cellular anatomical structure	4
SNARE complex	3
neurotransmitter secretion	2
positive regulation of secretion by cell	2
intracellular protein localization	2
vesicle-mediated transport	2
regulated exocytosis	2
presynapse	2
ion channel inhibitor activity	2
binding	2
cytoplasm	2
synapse	2
regulation of neurotransmitter secretion	1
positive regulation of synaptic transmission	1
positive regulation of neurotransmitter transport	1
protein transport	1
intracellular transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
vesicle organization	1
organelle membrane fusion	1
response to abiotic stimulus	1
regulation of norepinephrine secretion	1
positive regulation of catecholamine secretion	1
norepinephrine secretion	1
synaptic vesicle priming	1
regulation of protein-containing complex assembly	1
establishment of localization in cell	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
signal release from synapse	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
protein secretion	1
peptide hormone secretion	1
secretion	1
export from cell	1
catecholamine secretion	1
regulation of catecholamine secretion	1

Protein interactions and networks

STRING

2265 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STX1A	SNAP25	P13795	999
STX1A	VAMP2	P19065	999
STX1A	STXBP1	P61764	998
STX1A	SYT1	P21579	986
STX1A	SNAP23	O00161	971
STX1A	KCNB1	Q14721	962
STX1A	ST8SIA2	Q92186	940
STX1A	STXBP5	Q5T5C0	938
STX1A	VAMP1	P23763	935
STX1A	CPLX1	O14810	934
STX1A	KCNA1	Q09470	904
STX1A	CACNA1B	Q00975	898
STX1A	SLC6A2	P23975	888
STX1A	NAPA	P54920	888
STX1A	VAMP3	Q15836	871

IntAct

386 interactions, top by confidence:

A	B	Type	Score
SNAP25	VAMP2	psi-mi:“MI:0914”(association)	0.760
VAMP2	SNAP25	psi-mi:“MI:0914”(association)	0.760
SNAP25	VAMP2	psi-mi:“MI:0915”(physical association)	0.760
STX1A	NAPB	psi-mi:“MI:0915”(physical association)	0.670
STX1A	STX1A	psi-mi:“MI:0915”(physical association)	0.670
STX1A	TXLNA	psi-mi:“MI:0915”(physical association)	0.670
VAMP2	SNCA	psi-mi:“MI:0914”(association)	0.630
SNAP23	STX1A	psi-mi:“MI:0915”(physical association)	0.550
SNAP29	STX1A	psi-mi:“MI:0915”(physical association)	0.550
STX1A	SNAP23	psi-mi:“MI:0915”(physical association)	0.550
STX1A	SNAP29	psi-mi:“MI:0915”(physical association)	0.550
SNAP25	SNCA	psi-mi:“MI:0914”(association)	0.500
SNCA	SNAP25	psi-mi:“MI:0914”(association)	0.500
SNAP25	SNCA	psi-mi:“MI:0915”(physical association)	0.500
SNAP25	STX1A	psi-mi:“MI:0915”(physical association)	0.500
SNCA	STX1A	psi-mi:“MI:0915”(physical association)	0.500
DPP8	STX1A	psi-mi:“MI:0915”(physical association)	0.400
STX1A	PSMA3	psi-mi:“MI:0915”(physical association)	0.370
STX1A	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.370
STX1A	TXLNB	psi-mi:“MI:0915”(physical association)	0.370
STX1A	Stxbp1	psi-mi:“MI:2364”(proximity)	0.270
DISC1	STX1A	psi-mi:“MI:0915”(physical association)	0.000
STXBP1	STX1A	psi-mi:“MI:0915”(physical association)	0.000
MAL	STX1A	psi-mi:“MI:0915”(physical association)	0.000
TSNARE1	STX1A	psi-mi:“MI:0915”(physical association)	0.000
SMIM1	STX1A	psi-mi:“MI:0915”(physical association)	0.000
UPK1B	STX1A	psi-mi:“MI:0915”(physical association)	0.000
	STX1A	psi-mi:“MI:0915”(physical association)	0.000
TMEM128	STX1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (272): STXBP1 (Reconstituted Complex), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Two-hybrid), STX1A (Two-hybrid), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS), STX1A (Affinity Capture-MS)

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

8 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	STX1A	phosphorylation
DAPK1	“down-regulates activity”	STX1A	phosphorylation
STX1A	“form complex”	SNARE_complex	binding
CADPS	“up-regulates activity”	STX1A	binding
CADPS2	“up-regulates activity”	STX1A	binding
SYBU	“up-regulates activity”	STX1A	relocalization
CSNK2A2	unknown	STX1A	phosphorylation
STXBP1	“up-regulates activity”	STX1A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 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
Other interleukin signaling	5	36.0×	1e-05
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	5	36.0×	1e-05
Intra-Golgi traffic	6	23.6×	1e-05
Retrograde transport at the Trans-Golgi-Network	6	20.0×	2e-05
COPII-mediated vesicle transport	6	14.8×	1e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	8	12.7×	1e-05
ER-Phagosome pathway	6	11.8×	4e-04
ER to Golgi Anterograde Transport	5	10.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	12	86.7×	5e-19
vesicle fusion	14	79.5×	2e-21
synaptic vesicle priming	6	45.4×	3e-07
membrane fusion	7	41.2×	3e-08
exocytosis	11	15.8×	1e-08
long-term synaptic potentiation	5	13.2×	3e-03
cellular response to type II interferon	6	11.8×	1e-03
retrograde transport, endosome to Golgi	6	11.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	22
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1679128	NM_004603.4(STX1A):c.284-1G>A	Pathogenic
814991	GRCh37/hg19 7q11.23(chr7:72996564-73597315)x1	Pathogenic
1679129	NM_004603.4(STX1A):c.554C>G (p.Ser185Cys)	Likely pathogenic
1679130	NM_004603.4(STX1A):c.668_670del (p.Val223del)	Likely pathogenic
1679131	NM_004603.4(STX1A):c.677A>G (p.Gln226Arg)	Likely pathogenic
1679132	NM_004603.4(STX1A):c.722_724del (p.Val241del)	Likely pathogenic
984555	NM_004603.4(STX1A):c.435C>G (p.Cys145Trp)	Likely pathogenic

SpliceAI

2099 predictions. Top by Δscore:

Variant	Effect	Δscore
7:73700927:TGAGG:T	acceptor_gain	1.0000
7:73700928:GAGG:G	acceptor_gain	1.0000
7:73700930:GG:G	acceptor_gain	1.0000
7:73700932:C:CC	acceptor_gain	1.0000
7:73702840:CTCA:C	donor_loss	1.0000
7:73702841:TCA:T	donor_loss	1.0000
7:73702842:CA:C	donor_loss	1.0000
7:73702843:A:AC	donor_gain	1.0000
7:73702844:C:CC	donor_gain	1.0000
7:73702844:C:CG	donor_loss	1.0000
7:73702844:CCTGG:C	donor_gain	1.0000
7:73702982:TCT:T	acceptor_loss	1.0000
7:73702983:C:CC	acceptor_gain	1.0000
7:73702983:CTGG:C	acceptor_loss	1.0000
7:73702984:T:G	acceptor_loss	1.0000
7:73703750:CTCA:C	donor_loss	1.0000
7:73703751:TCA:T	donor_loss	1.0000
7:73703752:CA:C	donor_loss	1.0000
7:73703753:A:AC	donor_gain	1.0000
7:73703753:A:AG	donor_loss	1.0000
7:73703753:AC:A	donor_gain	1.0000
7:73703753:ACC:A	donor_gain	1.0000
7:73703754:C:CA	donor_loss	1.0000
7:73703754:C:CC	donor_gain	1.0000
7:73703754:CC:C	donor_gain	1.0000
7:73703754:CCC:C	donor_gain	1.0000
7:73703825:CCGG:C	acceptor_gain	1.0000
7:73703826:CGG:C	acceptor_gain	1.0000
7:73703826:CGGC:C	acceptor_gain	1.0000
7:73703829:C:CC	acceptor_gain	1.0000

AlphaMissense

1942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73700780:C:G	A247P	1.000
7:73700801:C:G	A240P	1.000
7:73702875:G:C	F216L	1.000
7:73702875:G:T	F216L	1.000
7:73702877:A:G	F216L	1.000
7:73702888:A:G	L212P	1.000
7:73702909:A:G	L205P	1.000
7:73704156:A:G	L153P	1.000
7:73704189:C:G	R142P	1.000
7:73704246:A:G	L123P	1.000
7:73700758:G:T	A254D	0.999
7:73700759:C:G	A254P	0.999
7:73700779:G:T	A247D	0.999
7:73700821:A:T	I233N	0.999
7:73700840:C:G	G227R	0.999
7:73700840:C:T	G227R	0.999
7:73702858:A:G	L222P	0.999
7:73702865:C:G	A220P	0.999
7:73702876:A:C	F216C	0.999
7:73702876:A:G	F216S	0.999
7:73702930:C:G	R198P	0.999
7:73703764:A:C	F177L	0.999
7:73703764:A:T	F177L	0.999
7:73703765:A:C	F177C	0.999
7:73703765:A:G	F177S	0.999
7:73703766:A:G	F177L	0.999
7:73703789:A:G	L169P	0.999
7:73703801:A:G	L165P	0.999
7:73704161:C:A	R151S	0.999
7:73704161:C:G	R151S	0.999

dbSNP variants (sampled 300 via entrez): RS1000259461 (7:73706967 G>C), RS1000307837 (7:73707159 G>A,C), RS1000468722 (7:73701729 C>T), RS1000821349 (7:73701399 G>A), RS1001769417 (7:73714882 C>T), RS1001821782 (7:73715495 C>T), RS1002100064 (7:73716827 G>C,T), RS1002155583 (7:73717099 G>A), RS1002263780 (7:73709752 G>A,C), RS1002378824 (7:73704117 G>A,C,T), RS1002422872 (7:73704480 C>A,T), RS1002706055 (7:73705476 C>T), RS1002741640 (7:73699673 G>A), RS1002758471 (7:73705717 A>C), RS1003836745 (7:73718600 C>A,T)

Disease associations

OMIM: gene MIM:186590 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal dominant
cystic fibrosis	Supportive	Autosomal recessive

Mondo (5): intellectual disability (MONDO:0001071), autism (MONDO:0005260), cystic fibrosis (MONDO:0009061), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

212 total (30 of 212 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000246	Sinusitis
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST010244_44	Triglyceride levels	8.000000e-45
GCST010725_13	Malaria	8.000000e-06
GCST010725_74	Malaria	6.000000e-06
GCST010725_91	Malaria	7.000000e-06
GCST90020028_167	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	increases expression, affects cotreatment, decreases expression	2
Arsenic	increases expression, affects methylation, increases abundance	2
Estradiol	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
methylselenic acid	affects expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Troglitazone	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00208078	PHASE4	TERMINATED	Effect of Non-Invasive Ventilation in Cystic Fibrosis Patient With Chronic Respiratory Failure.
NCT00244270	PHASE4	COMPLETED	Cystic Fibrosis and Totally Implantable Vascular Access Devices
NCT00333385	PHASE4	TERMINATED	Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
NCT00411736	PHASE4	COMPLETED	Scandinavian Cystic Fibrosis Azithromycin Study
NCT00418470	PHASE4	TERMINATED	Prolonging the Duration of Peripheral Venous Catheters in Cystic Fibrosis People
NCT00431964	PHASE4	COMPLETED	Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
NCT00434278	PHASE4	TERMINATED	A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)
NCT00483769	PHASE4	COMPLETED	One Year Glargine Treatment in CFRD Children and Adolescents
NCT00528190	PHASE4	COMPLETED	Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis
NCT00557089	PHASE4	COMPLETED	The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
NCT00572975	PHASE4	COMPLETED	Malabsorption Blood Test:Toward a Novel Approach to Quantify Steatorrhea
NCT00680316	PHASE4	TERMINATED	A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis
NCT00685035	PHASE4	COMPLETED	Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings
NCT00744250	PHASE4	TERMINATED	Intraduodenal Aspiration Study to Assess the Bioavailability of Oral Pancrecarb® Compared to Placebo Control
NCT00787917	PHASE4	TERMINATED	An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients With Cystic Fibrosis Complicated by Acute Bronchopulmonary Aspergillosis (ABPA)
NCT00843817	PHASE4	COMPLETED	RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
NCT00890370	PHASE4	COMPLETED	Should Any One Airway Clearance Technique be Recommended for People With Cystic Fibrosis?
NCT00996424	PHASE4	TERMINATED	The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
NCT01044719	PHASE4	UNKNOWN	Duration of Antibiotics in Infective Exacerbations of Cystic Fibrosis
NCT01100606	PHASE4	COMPLETED	A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age
NCT01131507	PHASE4	COMPLETED	PR-018: An Open-Label, Safety Extension of Study PR-011
NCT01207245	PHASE4	COMPLETED	Circadian Rhythm In Tobramycin Elimination In Cystic Fibrosis
NCT01323101	PHASE4	COMPLETED	Doxycycline Effects on Inflammation in Cystic Fibrosis
NCT01327703	PHASE4	COMPLETED	Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
NCT01377792	PHASE4	COMPLETED	Study of Long-term Treatment With Hypertonic Saline in Patients With Cystic Fibrosis
NCT01400750	PHASE4	COMPLETED	Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis
NCT01429259	PHASE4	COMPLETED	Population Pharmacokinetics of Prolonged Infusion Meropenem in Cystic Fibrosis (CF) Children
NCT01608555	PHASE4	COMPLETED	Tobramycin 300 mg Once-a-day (o.d.) Aerosol in Adults With Cystic Fibrosis
NCT01667094	PHASE4	UNKNOWN	A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
NCT01694069	PHASE4	TERMINATED	Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
NCT01702415	PHASE4	WITHDRAWN	Zoledronic Acid in Cystic Fibrosis
NCT01712334	PHASE4	COMPLETED	A Study of the Comparable Efficacy and Safety of Pulmozyme (Dornase Alfa) Delivered by the eRapid Nebulizer System in Patients With Cystic Fibrosis
NCT01737983	PHASE4	COMPLETED	Effect of Lactobacillus Reuteri in Cystic Fibrosis
NCT01844778	PHASE4	COMPLETED	Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
NCT01880346	PHASE4	COMPLETED	Comparison of Absorption of Vitamin D in Cystic Fibrosis
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT02015663	PHASE4	TERMINATED	Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
NCT02048592	PHASE4	UNKNOWN	Impact of Immunonutrition on the Patients With Cystic Fibrosis