STXBP3

Summary

STXBP3 (syntaxin binding protein 3, HGNC:11446) is a protein-coding gene on chromosome 1p13.3, encoding Syntaxin-binding protein 3 (O00186). Together with STX4 and VAMP2, may play a role in insulin-dependent movement of GLUT4 and in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes. It is a selective cancer dependency (DepMap: 26.2% of cell lines).

Enables syntaxin binding activity. Involved in negative regulation of calcium ion-dependent exocytosis; neutrophil degranulation; and platelet aggregation. Located in cytosol; plasma membrane; and secretory granule.

Source: NCBI Gene 6814 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn error of immunity (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 93 total — 3 likely-pathogenic
• Cancer dependency (DepMap): dependent in 26.2% of screened cell lines
• MANE Select transcript: NM_007269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11446
Approved symbol	STXBP3
Name	syntaxin binding protein 3
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	UNC-18C
Ensembl gene	ENSG00000116266
Ensembl biotype	protein_coding
OMIM	608339
Entrez	6814

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000370008, ENST00000469338, ENST00000472099, ENST00000483586, ENST00000485167, ENST00000486601, ENST00000495245, ENST00000889910, ENST00000889911, ENST00000889912, ENST00000889913, ENST00000889914, ENST00000889915, ENST00000889916, ENST00000934866, ENST00000946296, ENST00000946297

RefSeq mRNA: 1 — MANE Select: NM_007269 NM_007269

CCDS: CCDS790

Canonical transcript exons

ENST00000370008 — 19 exons

Exon	Start	End
ENSE00000782922	108796234	108796372
ENSE00000782923	108794827	108794907
ENSE00000782924	108793582	108793647
ENSE00000826648	108807401	108807549
ENSE00000958049	108779286	108779410
ENSE00000958050	108782422	108782517
ENSE00001024200	108796620	108796726
ENSE00001067191	108808783	108809523
ENSE00001217296	108758510	108758588
ENSE00001217301	108756690	108756766
ENSE00001875071	108746674	108746786
ENSE00003462311	108800220	108800305
ENSE00003492692	108776333	108776423
ENSE00003524099	108782649	108782706
ENSE00003569608	108798145	108798237
ENSE00003606995	108753063	108753144
ENSE00003664972	108759985	108760085
ENSE00003684390	108772665	108772819
ENSE00003688726	108752257	108752306

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.8733 / max 542.7415, expressed in 1806 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4366	28.8733	1806

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.19	gold quality
calcaneal tendon	UBERON:0003701	98.09	gold quality
tibia	UBERON:0000979	96.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.86	gold quality
germinal epithelium of ovary	UBERON:0001304	96.79	gold quality
epithelium of nasopharynx	UBERON:0001951	96.75	gold quality
spinal cord	UBERON:0002240	96.58	gold quality
inferior vagus X ganglion	UBERON:0005363	96.45	gold quality
monocyte	CL:0000576	96.32	gold quality
sural nerve	UBERON:0015488	96.19	gold quality
mononuclear cell	CL:0000842	96.18	gold quality
leukocyte	CL:0000738	95.86	gold quality
palpebral conjunctiva	UBERON:0001812	95.83	gold quality
subthalamic nucleus	UBERON:0001906	95.66	gold quality
visceral pleura	UBERON:0002401	95.35	gold quality
esophagus squamous epithelium	UBERON:0006920	95.30	gold quality
parietal pleura	UBERON:0002400	95.27	gold quality
medulla oblongata	UBERON:0001896	95.05	gold quality
choroid plexus epithelium	UBERON:0003911	94.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.79	gold quality
colonic mucosa	UBERON:0000317	94.77	gold quality
superior vestibular nucleus	UBERON:0007227	94.71	gold quality
pleura	UBERON:0000977	94.65	gold quality
cranial nerve II	UBERON:0000941	94.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.30	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.25	gold quality
substantia nigra	UBERON:0002038	94.14	gold quality
pons	UBERON:0000988	94.12	gold quality
midbrain	UBERON:0001891	94.10	gold quality
jejunal mucosa	UBERON:0000399	94.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

52 targeting STXBP3, 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-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7159-3P	99.51	70.17	1920

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Calpha activation and phosphorylation of syntaxin 4 and Munc18c are required for the cell surface expression of P-selectin and the consequent binding of neutrophils to endothelial cells. (PMID:15576373)
• Munc18-2 acts as a regulator of primary granule exocytosis, while Munc18-3 may preferentially regulate the fusion of secondary granules (PMID:18588921)
• These results indicate that insulin induces dynamic associations between PKCzeta, 80K-H, and munc18c and that 80K-H may act as a key signaling link between PKCzeta and munc18c in live cells. (PMID:19061073)
• The identify IR as the first known tyrosine kinase for Munc18c as part of a new insulin-signaling step in GLUT4 vesicle exocytosis. (PMID:21444687)
• Western Blot data showed decreased expression (p < 0,05) of Munc18c and phospho-PKC Zeta in polycystic ovary-insulin resistant endometria (PCOSE-IR) with respect to the control. (PMID:22390153)
• Munc18c gene expression in human adipose tissue is down-regulated in morbid obesity. (PMID:23700440)
• In vitro interaction assays indicated that Doc2b is required to bridge the interaction between Munc18c and Munc18-1 in the macromolecular complex; Munc18c and Munc18-1 failed to associate in the absence of Doc2b (PMID:25190515)
• PP2B-Aalpha-Munc18c complex supports agonist-induced VWF secretion by HUVECs. (PMID:28294518)
• Data suggest MUNC18C is required for STX4-mediated invadopodium formation and tumor invasion of extracellular matrix; N-terminal STX4 fragment binds to MUNC18C and inhibits interactions of STX4 with synaptosome-associated protein 23 (SNAP23) and vesicle-associated membrane protein 2 (VAMP2). Fibrosarcoma/adenocarcinoma cell lines were used in these studies. (MUNC18C = syntaxin binding protein MUNC18C; STX4 = syntaxin 4) (PMID:28798239)
• Pancreatic acini from Munc18c-depleted mice (Munc18c(+/-)) and human pancreas (lenti-Munc18c-shRNA-treated) exhibit normal apical exocytosis of zymogen granules (ZGs) in response to physiologic stimulation with the intestinal hormone cholecystokinin (CCK-8). (PMID:29284677)
• Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation. (PMID:33891011)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stxbp3	ENSDARG00000008142
mus_musculus	Stxbp3	ENSMUSG00000027882
rattus_norvegicus	Stxbp3	ENSRNOG00000020392
caenorhabditis_elegans		WBGENE00020298

Paralogs (7): STXBP2 (ENSG00000076944), SCFD1 (ENSG00000092108), VPS45 (ENSG00000136631), STXBP1 (ENSG00000136854), VPS33A (ENSG00000139719), VPS33B (ENSG00000184056), SCFD2 (ENSG00000184178)

Protein

Protein identifiers

Syntaxin-binding protein 3 — O00186 (reviewed: O00186)

Alternative names: Platelet Sec1 protein, Protein unc-18 homolog 3, Protein unc-18 homolog C

All UniProt accessions (1): O00186

UniProt curated annotations — full annotation on UniProt →

Function. Together with STX4 and VAMP2, may play a role in insulin-dependent movement of GLUT4 and in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes.

Subunit / interactions. Interacts with DOC2B; the interaction is direct, occurs at the cell membrane, excludes interaction with STX4 and regulates glucose-stimulated insulin secretion. Interacts with STX4.

Subcellular location. Cytoplasm. Cytosol. Cell membrane.

Tissue specificity. Megakaryocytes and platelets.

Post-translational modifications. Phosphorylated by PKC in platelets in response to thrombin stimulation; phosphorylation inhibits binding to STX4.

Similarity. Belongs to the STXBP/unc-18/SEC1 family.

RefSeq proteins (1): NP_009200* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001619	Sec1-like	Family
IPR027482	Sec1-like_dom2	Homologous_superfamily
IPR036045	Sec1-like_sf	Homologous_superfamily
IPR043127	Sec-1-like_dom3a	Homologous_superfamily
IPR043154	Sec-1-like_dom1	Homologous_superfamily

Pfam: PF00995

UniProt features (10 total): sequence conflict 5, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00186-F1	89.63	0.76

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114516	Disinhibition of SNARE formation
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-109582	Hemostasis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 268 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT

GO Biological Process (21): intracellular glucose homeostasis (GO:0001678), intracellular protein transport (GO:0006886), obsolete vesicle docking involved in exocytosis (GO:0006904), brain development (GO:0007420), protein to membrane docking (GO:0022615), insulin secretion (GO:0030073), response to insulin (GO:0032868), neutrophil degranulation (GO:0043312), negative regulation of calcium ion-dependent exocytosis (GO:0045955), negative regulation of D-glucose import across plasma membrane (GO:0046325), platelet aggregation (GO:0070527), cellular response to type II interferon (GO:0071346), presynaptic dense core vesicle exocytosis (GO:0099525), exocytosis (GO:0006887), response to stress (GO:0006950), immune response (GO:0006955), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), regulated exocytosis (GO:0045055), negative regulation of transport (GO:0051051), regulation of biological quality (GO:0065008)

GO Molecular Function (4): syntaxin-1 binding (GO:0017075), syntaxin binding (GO:0019905), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (13): cytosol (GO:0005829), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), secretory granule (GO:0030141), platelet alpha granule (GO:0031091), specific granule (GO:0042581), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), tertiary granule (GO:0070820), presynapse (GO:0098793), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Membrane Trafficking	1
Vesicle-mediated transport	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transport	3
secretory granule	3
intracellular protein localization	2
response to stimulus	2
binding	2
plasma membrane region	2
glucose homeostasis	1
intracellular chemical homeostasis	1
protein transport	1
intracellular transport	1
central nervous system development	1
animal organ development	1
head development	1
membrane docking	1
protein secretion	1
peptide hormone secretion	1
response to peptide hormone	1
neutrophil activation involved in immune response	1
neutrophil mediated immunity	1
leukocyte degranulation	1
calcium-ion regulated exocytosis	1
regulation of calcium ion-dependent exocytosis	1
negative regulation of regulated secretory pathway	1
negative regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
platelet activation	1
homotypic cell-cell adhesion	1
response to type II interferon	1
cellular response to cytokine stimulus	1
calcium ion-regulated exocytosis of neurotransmitter	1
neuronal dense core vesicle exocytosis	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
immune system process	1
establishment of protein localization	1
cellular process	1
exocytosis	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STXBP3	STX4	Q12846	999
STXBP3	VAMP2	P19065	889
STXBP3	SNAP23	O00161	868
STXBP3	VAMP8	Q9BV40	858
STXBP3	STX3	Q13277	811
STXBP3	SLC2A4	P14672	804
STXBP3	STX1A	Q16623	749
STXBP3	VAMP3	Q15836	744
STXBP3	STX2	P32856	739
STXBP3	NSF	P46459	702
STXBP3	STX1B	P61266	695
STXBP3	VAMP7	P51809	658
STXBP3	SNTG1	Q9NSN8	646
STXBP3	STX6	O43752	630
STXBP3	STX11	O75558	627

IntAct

89 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
STXBP3	STX4	psi-mi:“MI:0914”(association)	0.640
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ICMT	STXBP3	psi-mi:“MI:0914”(association)	0.530
TMEM97	STXBP3	psi-mi:“MI:0914”(association)	0.530
AAGAB	STXBP3	psi-mi:“MI:0914”(association)	0.530
GPR141	STXBP3	psi-mi:“MI:0914”(association)	0.530
PLPPR1	STXBP3	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
TMEM192	STXBP3	psi-mi:“MI:0914”(association)	0.530
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
SLC7A1	STXBP3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
STXBP3	SYNE2	psi-mi:“MI:0915”(physical association)	0.400
STXBP3	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (163): STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STX4 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS)

ESM2 similar proteins: B0XDC4, B2RY04, B3LF48, B3M383, B4GEU5, B4JT42, B4K5R2, B4NBB0, O00186, O08599, O18637, O74534, O94590, P22213, P30619, P34260, P34529, P34815, P38932, P61763, P61764, P61765, P97393, Q07327, Q14185, Q15833, Q16JS8, Q18891, Q24179, Q28288, Q296Q5, Q54QC8, Q5D892, Q5R6D2, Q5VNU3, Q60770, Q62753, Q64324, Q6R748, Q7QCW2

Diamond homologs: O00186, O08599, P34815, P61763, P61764, P61765, Q07327, Q15833, Q28288, Q29268, Q54QC8, Q5R6D2, Q60770, Q62753, Q64324, Q6R748, Q9SZ77, Q9C5X3, O94590, Q5VNU3, O74534, P22213, Q62991, Q7XWP3, Q8BRF7, Q8WVM8, Q9C5P7, Q9SL48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	61
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1879089	NM_007269.4(STXBP3):c.1029+2T>G	Likely pathogenic
3068187	NM_007269.4(STXBP3):c.622G>A (p.Ala208Thr)	Likely pathogenic
3378407	NM_007269.4(STXBP3):c.1029+1_1029+5del	Likely pathogenic

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
1:108746785:GA:G	donor_gain	1.0000
1:108746787:G:GG	donor_gain	1.0000
1:108752253:ACAG:A	acceptor_loss	1.0000
1:108752255:A:AG	acceptor_gain	1.0000
1:108752256:G:GC	acceptor_loss	1.0000
1:108752256:G:GG	acceptor_gain	1.0000
1:108752256:GA:G	acceptor_gain	1.0000
1:108752256:GAGAT:G	acceptor_gain	1.0000
1:108752303:GAAGG:G	donor_loss	1.0000
1:108752304:A:T	donor_gain	1.0000
1:108752304:AAGGT:A	donor_loss	1.0000
1:108752305:AGGTA:A	donor_loss	1.0000
1:108752306:GGTAG:G	donor_loss	1.0000
1:108752307:GTAGA:G	donor_loss	1.0000
1:108752308:T:A	donor_loss	1.0000
1:108753060:A:AG	acceptor_gain	1.0000
1:108753061:A:G	acceptor_gain	1.0000
1:108753062:G:GG	acceptor_gain	1.0000
1:108753062:GAT:G	acceptor_gain	1.0000
1:108753062:GATA:G	acceptor_gain	1.0000
1:108753062:GATAA:G	acceptor_gain	1.0000
1:108753144:GGTA:G	donor_loss	1.0000
1:108753145:G:A	donor_loss	1.0000
1:108753145:G:GG	donor_gain	1.0000
1:108753146:T:TC	donor_loss	1.0000
1:108756688:A:AG	acceptor_gain	1.0000
1:108756689:G:GC	acceptor_gain	1.0000
1:108756689:GTT:G	acceptor_gain	1.0000
1:108756689:GTTGT:G	acceptor_gain	1.0000
1:108756763:AAAGG:A	donor_loss	1.0000

AlphaMissense

3936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:108779305:T:C	L235P	0.999
1:108782490:G:C	R293P	0.999
1:108796238:T:C	L372P	0.999
1:108796349:T:C	L409P	0.999
1:108798208:T:A	W474R	0.999
1:108798208:T:C	W474R	0.999
1:108756713:C:A	R69S	0.998
1:108772779:T:C	C185R	0.998
1:108776371:T:A	V211D	0.998
1:108776383:T:C	L215P	0.998
1:108779311:T:A	I237K	0.998
1:108782477:T:A	W289R	0.998
1:108782477:T:C	W289R	0.998
1:108794859:C:G	C354W	0.998
1:108794907:G:C	Q370H	0.998
1:108794907:G:T	Q370H	0.998
1:108796341:A:C	R406S	0.998
1:108796341:A:T	R406S	0.998
1:108796694:T:A	W442R	0.998
1:108796694:T:C	W442R	0.998
1:108807499:G:C	R545P	0.998
1:108753076:A:T	D38V	0.997
1:108756743:T:G	Y79D	0.997
1:108759987:T:C	C114R	0.997
1:108779311:T:G	I237R	0.997
1:108779349:C:G	H250D	0.997
1:108779383:T:C	L261P	0.997
1:108782479:G:C	W289C	0.997
1:108782479:G:T	W289C	0.997
1:108796340:G:C	R406T	0.997

dbSNP variants (sampled 300 via entrez): RS1000060587 (1:108774866 T>C), RS1000083808 (1:108790525 A>G), RS1000195692 (1:108746622 T>C), RS1000315146 (1:108750813 C>T), RS1000399297 (1:108777104 G>A), RS1000404384 (1:108777446 T>C), RS1000436588 (1:108797445 C>T), RS1000607010 (1:108799476 A>G), RS1000617901 (1:108793032 C>T), RS1000647517 (1:108784222 G>A), RS1000672057 (1:108800994 T>A), RS1000773534 (1:108809121 C>T), RS1000779736 (1:108802516 A>G), RS1000863377 (1:108758018 G>A), RS1000869645 (1:108750662 G>A)

Disease associations

OMIM: gene MIM:608339 | disease phenotypes: MIM:620514

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn error of immunity	Strong	Autosomal recessive

Mondo (2): immune dysregulation, autoimmunity, and autoinflammation (MONDO:0957790), inborn error of immunity (MONDO:0003778)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001343_2	Fat distribution (HIV)	5.000000e-06
GCST001343_5	Fat distribution (HIV)	1.000000e-06
GCST001343_8	Fat distribution (HIV)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007153	Immunologic Deficiency Syndromes	C20.673

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases methylation, increases expression	3
perfluorooctane sulfonic acid	decreases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
K 7174	increases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
MT19c compound	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Bile Acids and Salts	increases expression	1
Cisplatin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nicotine	increases expression	1
Serotonin	affects secretion	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00468273	PHASE3	COMPLETED	A Clinical Study of Intravenous Immunoglobulin
NCT00811174	PHASE3	TERMINATED	Efficacy, Safety and Kinetics Study of Octagam 10% in Primary Immunodeficiency Diseases
NCT01012323	PHASE3	COMPLETED	A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
NCT01313507	PHASE3	COMPLETED	High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam)
NCT01406470	PHASE3	COMPLETED	Phase 3 Study of Immune Globulin Intravenous (Human)IVIG-SN™ in Subjects With Primary Immunodeficiency
NCT02783482	PHASE3	COMPLETED	Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency
NCT02810444	PHASE3	COMPLETED	Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID
NCT03961009	PHASE3	COMPLETED	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients
NCT04842643	PHASE3	COMPLETED	An Extension Study of TAK-664 for Japanese People With Primary Immunodeficiency Disease
NCT04944979	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)
NCT06089122	PHASE3	UNKNOWN	Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG
NCT06150833	PHASE3	UNKNOWN	Efficacy and Safety and Pharmacokinetics of Boya IVIG
NCT07346859	PHASE3	RECRUITING	Study of BP-SCIG 20% in Patients With Primary Immunodeficiency (PID)
NCT00001438	PHASE2	COMPLETED	A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
NCT00176865	PHASE2	COMPLETED	Stem Cell Transplant for Immunologic or Histiocytic Disorders
NCT00389324	PHASE2	COMPLETED	A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency
NCT00598481	PHASE2	COMPLETED	ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
NCT01856582	PHASE2	TERMINATED	CD34+ Stem Cell Infusion to Augment Graft Function
NCT06199427	PHASE2	RECRUITING	PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity
NCT00001158	Not specified	COMPLETED	Studies of the Immune Response in Normal Subjects and Patients With Disorders of the Immune System
NCT00001336	Not specified	COMPLETED	In Vitro Studies of Immunological and Stem Cell Function in Peripheral Blood Mononuclear Cells in Patients
NCT00001788	Not specified	TERMINATED	Genetic Basis of Primary Immunodeficiencies
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006131	Not specified	COMPLETED	Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients With Uncomplicated Herpes Zoster
NCT01150240	Not specified	UNKNOWN	Clinical and Laboratory Online Patient- and Research Database for Primary Immunodeficiencies in Switzerland
NCT01727895	Not specified	COMPLETED	Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans
NCT02176239	Not specified	COMPLETED	Monitoring of 5% Treatment Naïve Intravenous Immunoglobulin (IVIg) Primary Immunodeficiency Disease (PIDD) Patients Using the CareExchange® System: A Pilot Study Using 5% Gammaplex® IVIg in the Home Setting
NCT02417740	Not specified	RECRUITING	Natural History of Noncirrhotic Portal Hypertension
NCT02554630	Not specified	COMPLETED	Novel Mechanisms and Approaches to Treat Neonatal Sepsis
NCT02630082	Not specified	COMPLETED	Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru
NCT02735824	Not specified	RECRUITING	Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies
NCT03252548	Not specified	UNKNOWN	Pediatric Primary Immunodeficiency Disease (PID) in China
NCT03478670	Not specified	ENROLLING_BY_INVITATION	Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
NCT03835312	Not specified	RECRUITING	Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM
NCT03920735	Not specified	UNKNOWN	Retrospective Non-interventional Analysis of Opportunistic Infections in Immunocompromised and Frail Patients
NCT04798677	Not specified	COMPLETED	Efficacy and Tolerability of ABBC1 in Volunteers Receiving the Influenza or Covid-19 Vaccine
NCT05236764	Not specified	ACTIVE_NOT_RECRUITING	Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion