ITSN1

Summary

ITSN1 (intersectin 1, HGNC:6183) is a protein-coding gene on chromosome 21q22.11, encoding Intersectin-1 (Q15811). Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery.

The protein encoded by this gene is a cytoplasmic membrane-associated protein that indirectly coordinates endocytic membrane traffic with the actin assembly machinery. In addition, the encoded protein may regulate the formation of clathrin-coated vesicles and could be involved in synaptic vesicle recycling. This protein has been shown to interact with dynamin, CDC42, SNAP23, SNAP25, SPIN90, EPS15, EPN1, EPN2, and STN2. Multiple transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been characterized so far.

Source: NCBI Gene 6453 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 468 total — 17 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6183
Approved symbol	ITSN1
Name	intersectin 1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	SH3P17, MGC134948, MGC134949
Ensembl gene	ENSG00000205726
Ensembl biotype	protein_coding
OMIM	602442
Entrez	6453

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 15 protein_coding, 7 retained_intron, 6 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000379960, ENST00000381283, ENST00000381284, ENST00000381291, ENST00000381318, ENST00000399338, ENST00000399349, ENST00000399352, ENST00000399353, ENST00000399355, ENST00000399367, ENST00000415023, ENST00000419241, ENST00000420666, ENST00000428240, ENST00000437126, ENST00000440794, ENST00000444491, ENST00000451686, ENST00000456489, ENST00000462212, ENST00000465143, ENST00000470742, ENST00000472548, ENST00000474132, ENST00000475422, ENST00000479424, ENST00000487427, ENST00000488166, ENST00000489261, ENST00000495656

RefSeq mRNA: 7 — MANE Select: NM_003024 NM_001001132, NM_001331008, NM_001331009, NM_001331010, NM_001331011, NM_001331012, NM_003024

CCDS: CCDS33545, CCDS33546, CCDS82661, CCDS82663, CCDS82664, CCDS82665, CCDS82666

Canonical transcript exons

ENST00000381318 — 40 exons

Exon	Start	End
ENSE00001844175	33888152	33899861
ENSE00001867436	33642501	33642713
ENSE00002286409	33818267	33818472
ENSE00002289133	33772061	33772323
ENSE00002294975	33799808	33799929
ENSE00002306218	33751810	33751906
ENSE00002528364	33802430	33802444
ENSE00003481950	33856736	33856857
ENSE00003487819	33829624	33829745
ENSE00003507202	33882243	33882455
ENSE00003516373	33858686	33858792
ENSE00003520853	33875354	33875521
ENSE00003529805	33867233	33867331
ENSE00003535724	33885439	33885522
ENSE00003543412	33885041	33885123
ENSE00003550586	33819241	33819323
ENSE00003554783	33718797	33718856
ENSE00003559784	33823487	33823653
ENSE00003560708	33765875	33766012
ENSE00003582731	33767713	33767828
ENSE00003590878	33883550	33883671
ENSE00003604372	33826818	33826863
ENSE00003615598	33755297	33755397
ENSE00003626830	33836441	33836632
ENSE00003629591	33813913	33814072
ENSE00003636097	33721178	33721270
ENSE00003644095	33865151	33865334
ENSE00003660532	33761923	33761986
ENSE00003673780	33886287	33886460
ENSE00003694267	33834307	33834424
ENSE00003711579	33750143	33750322
ENSE00003716255	33781994	33782133
ENSE00003716800	33794341	33794468
ENSE00003722466	33797379	33797608
ENSE00003727180	33722588	33722651
ENSE00003740685	33774968	33775108
ENSE00003746393	33810975	33811222
ENSE00003748649	33781461	33781548
ENSE00003754038	33774729	33774878
ENSE00003789821	33735044	33735204

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7475 / max 358.8404, expressed in 1719 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188885	10.0425	1574
188884	4.5564	1389
188883	1.3389	770
188894	0.9140	358
188893	0.4010	188
188887	0.1841	59
188888	0.1810	18
188889	0.0681	16
188886	0.0616	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.13	gold quality
tibia	UBERON:0000979	96.78	gold quality
cortical plate	UBERON:0005343	96.36	gold quality
saphenous vein	UBERON:0007318	96.34	gold quality
parietal pleura	UBERON:0002400	95.70	gold quality
cranial nerve II	UBERON:0000941	95.63	gold quality
adipose tissue	UBERON:0001013	95.32	gold quality
pericardium	UBERON:0002407	95.31	gold quality
connective tissue	UBERON:0002384	94.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.48	gold quality
ganglionic eminence	UBERON:0004023	94.44	gold quality
peritoneum	UBERON:0002358	94.31	gold quality
omental fat pad	UBERON:0010414	94.31	gold quality
pleura	UBERON:0000977	94.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.22	gold quality
embryo	UBERON:0000922	93.94	gold quality
vena cava	UBERON:0004087	93.40	gold quality
mammary gland	UBERON:0001911	93.29	gold quality
thoracic mammary gland	UBERON:0005200	93.29	gold quality
endothelial cell	CL:0000115	93.19	gold quality
ventricular zone	UBERON:0003053	93.18	gold quality
stromal cell of endometrium	CL:0002255	92.94	gold quality
mammary duct	UBERON:0001765	92.66	gold quality
visceral pleura	UBERON:0002401	92.66	gold quality
calcaneal tendon	UBERON:0003701	92.57	gold quality
tibial nerve	UBERON:0001323	92.56	gold quality
synovial joint	UBERON:0002217	92.53	gold quality
myometrium	UBERON:0001296	92.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	10.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1, FLI1, GTF2I, SNAI1, TP53

miRNA regulators (miRDB)

56 targeting ITSN1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-3184-5P	98.56	67.13	1491

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 36)

• intersectin interaction with dynamin was important in regulating the fission and internalization of caveolae (PMID:12960435)
• review of roles of ITSN1 and DSCR1 in Down syndrome, Alzheimer’s disease, endocytosis and vesicle trafficking (PMID:16442855)
• Results extend the current role of intersectin-1L in endocytosis to a function in exocytosis and support the idea that intersectin-1L is an adaptor that coordinates exo-endocytotic membrane trafficking in secretory cells. (PMID:16874303)
• ITSN forms a complex with Cbl in vivo mediated by the Src homology (SH) 3 domains binding to the Pro-rich COOH terminus of Cbl. This interaction stimulates the ubiquitylation and degradation of the activated EGFR. (PMID:16914641)
• findings demonstrate a novel role of ITSN-1s as a negative regulator of the mitochondrial pathway-dependent apoptosis secondary to activation of the Erk1/2 survival signaling pathway (PMID:17405881)
• These results demonstrate that alternative splicing leads to the formation of two pools of ITSN1 with potentially different properties in neurons, affecting ITSN1 function as adaptor protein. (PMID:18539136)
• These data provide a molecular link between SHIP2 and ITSN1 which are involved in receptor endocytosis regulation. (PMID:18692052)
• Intersectin 1 forms a complex with adaptor protein (SH3KBP1 protein), implicated in downregulation of receptor tyrosine kinases. (PMID:19166927)
• The higher exchange activity of ITSN1L towards the GDP-bound conformation of Cdc42 could represent an evolutionary adaptation of this GEF that ensures nucleotide exchange towards the formation of the signalling-active GTP-bound form of Cdc42. (PMID:19356586)
• The identification of fifteen novel transcriptional isoforms of the human ITSN1 gene with full-length coding sequences , is reported. (PMID:19777371)
• Downregulation of intersectin-1s induces apoptosis of brain glioblastoma cells. (PMID:20493827)
• microexons provide a mechanism for the control of tissue-specific interactions of ITSN1 and Src with their partners. (PMID:20659428)
• Studied the inhibitory mechanism of ITSN1L, & id’d a novel short amino acid motif which mediates autoinhibition. Found this motif is located in the SH3 DH linker region, and show that W1221 acts as key residue in establishing inhibitory interaction. (PMID:20842712)
• These findings expand the role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes. (PMID:20946875)
• ITSN-1s, via its SH3A domain has the unique ability to regulate dyn2 assembly-disassembly and function during endocytosis (PMID:21129155)
• ITSN1 has two isoforms: ITSN1-long and ITSN1-short. siRNA-mediated down regulation of ITSN1-short inhibits migration and invasion of glioma cells. (PMID:21503949)
• This novel mammalian ITSN1 isoform possesses a significantly altered domain structure and performs specific protein-protein interactions. (PMID:21712076)
• study reveals a link between overexpression of specific ITSN1 isoforms and behavioral phenotypes (PMID:21876463)
• Silencing ITSN1 significantly inhibits the anchorage independent growth of tumor cells in vitro. (PMID:22266851)
• the neuron-specific isoform of the stable tubule-only polypeptide (STOP) interacts with SH3A domain of ITSN1. (PMID:22750298)
• ITSN1 and ITSN2 bind similar proline-rich ligands but are differentially recognized by SH2 domain-containing proteins. (PMID:23936226)
• Our observations suggest that ITSN1 is an important general regulator of Cdc42-, Nck- and N-WASP-dependent actin polymerisation (PMID:24284073)
• Abnormal expression of the intersectin1-L protein in epileptic brain tissue may play an important role in epilepsy, especially refractory epilepsy. (PMID:25783631)
• Study suggests critical roles of ITSN1-S in malignant glioma proliferation, indicating a potential usage of ITSN1-S in the therapeutic intervention as a novel molecular target (PMID:25832561)
• study reports that vaccinia virus A36 contains three NPF motifs that interact with the Eps15 homology (EH) domains in intersectin-1 and Eps15 to promote the release of virus from infected cells and their subsequent spread (PMID:27670116)
• These findings provide the basis for further functional investigations of the ITSN/CR16 complex that may play an important role in actin remodeling and cellular invasion. (PMID:28161632)
• Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis. (PMID:28787396)
• Here, we discover that intersectin-s binds DENND2B, a guanine nucleotide exchange factor for the exocytic GTPase Rab13, and this interaction promotes recycling of ligand-free EGFR to the cell surface. Our study thus reveals a novel mechanism controlling the fate of internalized EGFR with important implications for cancer. (PMID:29030480)
• Different modes of ubiquitination regulated by AIP4 have opposite effects on ITSN1 isoform stability. (PMID:29851086)
• WIP enhances the interaction of N-WASP with ITSN1 and promotes ITSN1/beta-actin association. (PMID:29958948)
• the long isoform of intersectin-1 (ITSN-1), a guanine nucleotide exchange factor for Cdc42, is identified as a novel Golgi component and an interaction partner of GCC88 responsible for mediating the actin-dependent dispersal of the Golgi ribbon. (PMID:30540523)
• two isoforms of intersectin1 ITSN1-S and ITSN1-L produced by alternative splicing exerted opposite functions in glioma development. (PMID:31160551)
• ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs. (PMID:32780150)
• Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer. (PMID:34625530)
• ITSN1: a novel candidate gene involved in autosomal dominant neurodevelopmental disorder spectrum. (PMID:34707297)
• The alternative splicing of intersectin 1 regulated by PTBP1 promotes human glioma progression. (PMID:36171198)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	itsn1	ENSDARG00000000086
mus_musculus	Itsn1	ENSMUSG00000022957
rattus_norvegicus	Itsn1	ENSRNOG00000002001
drosophila_melanogaster	Dap160	FBGN0023388
drosophila_melanogaster	Eps-15	FBGN0035060
caenorhabditis_elegans		WBGENE00001224
caenorhabditis_elegans		WBGENE00006405

Paralogs (10): EHD3 (ENSG00000013016), EHD2 (ENSG00000024422), EPS15 (ENSG00000085832), EHD4 (ENSG00000103966), EHD1 (ENSG00000110047), EPS15L1 (ENSG00000127527), REPS1 (ENSG00000135597), REPS2 (ENSG00000169891), SRL (ENSG00000185739), ITSN2 (ENSG00000198399)

Protein

Protein identifiers

Intersectin-1 — Q15811 (reviewed: Q15811)

Alternative names: SH3 domain-containing protein 1A, SH3P17

All UniProt accessions (12): Q15811, C9J1A4, C9JQZ7, C9JXS9, F8W7U0, H0Y3G5, H0Y523, H0Y6W3, H0Y7J7, H7C3F1, H7C429, Q6J334

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery. Acts as a guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex. Plays a role in the assembly and maturation of clathrin-coated vesicles. Recruits FCHSD2 to clathrin-coated pits. Involved in endocytosis of activated EGFR, and probably also other growth factor receptors. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways. In chromaffin cells, required for normal exocytosis of catecholamines. Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones. Inhibits ARHGAP31 activity toward RAC1. Plays a role in synaptic vesicle endocytosis in brain neurons.

Subunit / interactions. Interacts (via DH domain) with CDC42. Interacts (via SH3 domain 1) with WASL. Interacts with dynamin, SNAP25 and SNAP23. Interacts with clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31. Interacts with ADAM15. Interacts with PRRT2. Interacts (via SH3 domain 4) with FCHSD2 (via SH3 domain 2). Interacts (via SH3 domain 1) with DENND2B. Interacts (via SH3 domains) with CBL. Isoform 2: Interacts with CBL and DNM1. Isoform 2: Interacts with LMNA. Isoform 2: Interacts with importin subunit KPNA1; this is likely to mediate its import into the nucleus. Interacts with DNM2. (Microbial infection) Interacts with vaccinia virus protein A36.

Subcellular location. Endomembrane system. Synapse. Synaptosome. Cell projection. Lamellipodium. Cell membrane. Membrane. Clathrin-coated pit. Recycling endosome. Endosome. Cytoplasmic vesicle Cytoplasm. Nucleus envelope Endomembrane system.

Tissue specificity. Isoform 1 is expressed almost exclusively in the brain. Isoform 2 is detected in brain, spleen, lung, liver, heart, skeletal muscle and kidney. Isoform 5 is primarily expressed in brain, spleen, lung and kidney (at protein level). Isoform 1 and isoform 2 are detected in brain. Isoform 2 is ubiquitous in adult and fetal tissues with high expression in skeletal muscle, heart, spleen, ovary, testis and all fetal tissues tested and low expression in thymus, blood, lung, liver and pancreas. Isoform 1 is expressed almost exclusively in the brain, in all brain regions. Not expressed in the spinal cord.

Domain organisation. SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin. SH3-1 and SH3-4 bind to ARHGAP31. The KLERQ domain binds to SNAP-25 and SNAP-23. In an autoinhibited form the SH3 domain 5 may bind intramolecularly to the DH domain, thus blocking the CDC42-binding site.

Miscellaneous. Contains a premature stop codon, potentially subjected to NMD. Contains a premature stop codon, potentially subjected to NMD.

Isoforms (13)

UniProt ID	Names	Canonical?
Q15811-1	1, Long, ITSN-l	yes
Q15811-2	2, Short, ITSN-s
Q15811-3	3, Short 2, SH3P17
Q15811-4	4
Q15811-5	5, ITSN1-22a
Q15811-6	6, Long form variant 4, Short form variant 11
Q15811-7	7, Short form variant 5
Q15811-8	8, Long form variant 2
Q15811-9	9, Long form variant 3
Q15811-10	10, Short form variant 2
Q15811-11	11, Short form variant 3
Q15811-12	12, Short form variant 10
Q15811-13	13, Short form variant 14

RefSeq proteins (7): NP_001001132, NP_001317937, NP_001317938, NP_001317939, NP_001317940, NP_001317941, NP_003015* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000219	DH_dom	Domain
IPR000261	EH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR032140	INTAP	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051480	Endocytic_GEF_Adapter	Family

Pfam: PF00018, PF00168, PF00621, PF07653, PF12763, PF14604, PF16617, PF16652

UniProt features (137 total): strand 37, helix 28, binding site 13, modified residue 13, domain 12, splice variant 11, sequence conflict 7, region of interest 5, mutagenesis site 4, turn 2, chain 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
3FIA	X-RAY DIFFRACTION	1.45
6H5T	X-RAY DIFFRACTION	1.69
4IIM	X-RAY DIFFRACTION	1.8
1KI1	X-RAY DIFFRACTION	2.3
5HZI	X-RAY DIFFRACTION	2.6
5HZJ	X-RAY DIFFRACTION	2.6
3QBV	X-RAY DIFFRACTION	2.65
5HZK	X-RAY DIFFRACTION	3.3
6GBU	X-RAY DIFFRACTION	3.44
2KGR	SOLUTION NMR
2KHN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15811-F1	73.28	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (13): 66; 68; 70; 72; 77; 267; 269; 271; 273; 278; 1667; 1670 …

Post-translational modifications (13): 203, 318, 687, 897, 901, 902, 904, 978, 986, 995, 1137, 1144, 1645

Mutagenesis-validated functional residues (4):

Position	Phenotype
1078	abolishes interaction with fchsd2.
1119	abolishes interaction with fchsd2.
1369	decreases specificity for cdc42; when associated with i-1376.
1376	decreases specificity for cdc42; when associated with l-1369.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199991	Membrane Trafficking
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-422475	Axon guidance
R-HSA-5653656	Vesicle-mediated transport
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 407 (showing top): GOBP_DENDRITE_DEVELOPMENT, RRAGTTGT_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_HORMONE_LEVELS, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MODULE_16, ACTGCAG_MIR173P

GO Biological Process (15): exocytosis (GO:0006887), intracellular protein localization (GO:0008104), protein transport (GO:0015031), endosomal transport (GO:0016197), intracellular signal transduction (GO:0035556), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of growth hormone secretion (GO:0060124), positive regulation of dendritic spine development (GO:0060999), regulation of postsynapse organization (GO:0099175), clathrin-dependent synaptic vesicle endocytosis (GO:0150007), regulation of modification of postsynaptic actin cytoskeleton (GO:1905274), positive regulation of caveolin-mediated endocytosis (GO:2001288), endocytosis (GO:0006897), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051)

GO Molecular Function (7): guanyl-nucleotide exchange factor activity (GO:0005085), calcium ion binding (GO:0005509), protein-macromolecule adaptor activity (GO:0030674), molecular adaptor activity (GO:0060090), proline-rich region binding (GO:0070064), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (23): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), lamellipodium (GO:0030027), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), recycling endosome (GO:0055037), apical dendrite (GO:0097440), intracellular vesicle (GO:0097708), postsynaptic endocytic zone (GO:0098843), postsynaptic actin cytoskeleton (GO:0098871), glutamatergic synapse (GO:0098978), nucleus (GO:0005634), endosome (GO:0005768), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
RHO GTPase cycle	3
Signal Transduction	2
Cell death signalling via NRAGE, NRIF and NADE	1
EPH-Ephrin signaling	1
GPCR downstream signalling	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Vesicle-mediated transport	1
p75 NTR receptor-mediated signalling	1
Axon guidance	1
Signaling by GPCR	1
Nervous system development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
vesicle-mediated transport	3
intracellular anatomical structure	3
endomembrane system	3
postsynapse	3
intracellular transport	2
protein binding	2
binding	2
cytoplasm	2
membrane	2
dendrite	2
intracellular membrane-bounded organelle	2
secretion by cell	1
vesicle fusion to plasma membrane	1
macromolecule localization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
signal transduction	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
growth hormone secretion	1
regulation of growth hormone secretion	1
positive regulation of peptide hormone secretion	1
positive regulation of developmental process	1
dendritic spine development	1
regulation of dendritic spine development	1
regulation of synapse organization	1
postsynapse organization	1
synaptic vesicle recycling via endosome	1
synaptic vesicle endocytosis	1
clathrin-dependent endocytosis	1
modification of postsynaptic actin cytoskeleton	1
regulation of modification of postsynaptic structure	1
positive regulation of endocytosis	1
caveolin-mediated endocytosis	1
regulation of caveolin-mediated endocytosis	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1

Protein interactions and networks

STRING

2614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITSN1	FCHO1	O14526	998
ITSN1	WASL	O00401	993
ITSN1	CDC42	P21181	993
ITSN1	EPS15	P42566	983
ITSN1	EPN2	O95208	979
ITSN1	STON2	Q8WXE9	978
ITSN1	EPN3	Q9H201	968
ITSN1	FCHO2	Q0JRZ9	960
ITSN1	SYNJ1	O43426	929
ITSN1	DNM1	Q05193	928
ITSN1	EPHB2	P29323	912
ITSN1	AMPH	P49418	900
ITSN1	GCC1	Q96CN9	891
ITSN1	BIN1	O00499	890
ITSN1	RABIF	P47224	861

IntAct

203 interactions, top by confidence:

A	B	Type	Score
CBL	EGFR	psi-mi:“MI:0403”(colocalization)	0.960
DNM2	ITSN1	psi-mi:“MI:0915”(physical association)	0.780
DNM2	ITSN1	psi-mi:“MI:0407”(direct interaction)	0.780
AP2B1	ITSN1	psi-mi:“MI:0407”(direct interaction)	0.760
DNM2	DNM1	psi-mi:“MI:0914”(association)	0.740
ITSN1	CBL	psi-mi:“MI:0915”(physical association)	0.730
CBL	ITSN1	psi-mi:“MI:0915”(physical association)	0.730
CBL	ITSN1	psi-mi:“MI:0403”(colocalization)	0.730
ITSN1	CBL	psi-mi:“MI:0403”(colocalization)	0.730
ITSN1	SOS1	psi-mi:“MI:0914”(association)	0.720
SOS1	ITSN1	psi-mi:“MI:0915”(physical association)	0.720
ITSN1	SOS1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ITSN1	WASL	psi-mi:“MI:0915”(physical association)	0.700
WASL	ITSN1	psi-mi:“MI:0407”(direct interaction)	0.700
WASL	ITSN1	psi-mi:“MI:0915”(physical association)	0.700
WASL	ITSN1	psi-mi:“MI:0403”(colocalization)	0.700

BioGRID (371): ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), EPS15 (Co-fractionation), EPS15L1 (Co-fractionation), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (FRET), ITSN1 (Affinity Capture-Western), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS), ITSN1 (Affinity Capture-MS)

ESM2 similar proteins: A6QP06, A7KAX9, F1LRS8, F1QIC4, G5EBZ8, O18195, O42287, O43432, O43491, O60237, O75167, O76337, O82171, O94519, O97902, P11171, P11434, P34416, P41110, P41993, P48820, Q09459, Q15811, Q1AAU6, Q501J7, Q52KW0, Q5HYK7, Q5M775, Q5RAU1, Q5RDE1, Q69ZW3, Q6NZJ6, Q801E2, Q8BG95, Q8IZ21, Q8R550, Q91X43, Q925Q9, Q96B97, Q9HCH5

Diamond homologs: A0A8I3PDQ1, A1CEK6, A1DFN5, A2QW93, A4FU49, A4RF61, A7A261, O13736, O35177, O35179, O35964, O42287, O43281, P29355, P34109, P38753, P43603, P56945, Q08012, Q0CJU8, Q0P5B1, Q0U6X7, Q14511, Q15811, Q16584, Q1E878, Q2GT05, Q4R729, Q4WHP5, Q557J6, Q5BBL4, Q5I1X5, Q61140, Q62419, Q62420, Q63767, Q64355, Q66HA1, Q6BNP6, Q6C2N2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ITSN1	up-regulates	CDC42	binding
GCC1	“up-regulates activity”	ITSN1	relocalization
ITSN1	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
“AP-2 complex”	“up-regulates activity”	ITSN1	binding
ITSN1	“up-regulates quantity by stabilization”	“AP-2/clathrin vescicle”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	6	32.0×	1e-06
The role of Nef in HIV-1 replication and disease pathogenesis	6	32.0×	1e-06
Nephrin family interactions	6	24.0×	6e-06
LDL clearance	5	22.9×	7e-05
RHOU GTPase cycle	9	21.1×	5e-08
Plasma lipoprotein clearance	5	20.0×	1e-04
RHOV GTPase cycle	8	19.2×	6e-07
EGFR downregulation	6	17.4×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle endocytosis	10	28.8×	1e-09
negative regulation of epidermal growth factor receptor signaling pathway	5	25.5×	3e-04
clathrin-dependent endocytosis	6	23.2×	6e-05
endocytosis	13	8.2×	3e-06
protein-containing complex assembly	8	6.1×	7e-03
intracellular protein transport	10	4.3×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	6
Uncertain significance	297
Likely benign	58
Benign	53

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1708060	NM_003024.3(ITSN1):c.473del (p.Leu158fs)	Pathogenic
2423448	NC_000021.8:g.(?35183279)(35191627_?)del	Pathogenic
2599271	NM_003024.3(ITSN1):c.2895C>G (p.Tyr965Ter)	Pathogenic
3340324	NM_003024.3(ITSN1):c.1102C>T (p.Arg368Ter)	Pathogenic
3342924	NM_003024.3(ITSN1):c.1660C>T (p.Gln554Ter)	Pathogenic
3360025	NM_003024.3(ITSN1):c.1333C>T (p.Arg445Ter)	Pathogenic
3376127	NM_003024.3(ITSN1):c.4248_4249del (p.Cys1417fs)	Pathogenic
3773994	NM_003024.3(ITSN1):c.3038dup (p.Tyr1013Ter)	Pathogenic
3861990	NM_003024.3(ITSN1):c.1271_1272del (p.Glu424fs)	Pathogenic
4040563	NM_003024.3(ITSN1):c.2070_2071del (p.Lys691fs)	Pathogenic
4072679	NM_003024.3(ITSN1):c.1651C>T (p.Gln551Ter)	Pathogenic
4075619	NM_003024.3(ITSN1):c.1363C>T (p.Gln455Ter)	Pathogenic
4086505	NM_003024.3(ITSN1):c.3113G>A (p.Trp1038Ter)	Pathogenic
4088969	NM_003024.3(ITSN1):c.973del (p.Ser324_Val325insTer)	Pathogenic
4530574	NM_003024.3(ITSN1):c.795_798del (p.Ser266fs)	Pathogenic
4726145	NM_003024.3(ITSN1):c.2400T>G (p.Tyr800Ter)	Pathogenic
4730448	NM_003024.3(ITSN1):c.3712C>T (p.Arg1238Ter)	Pathogenic
1707525	NM_003024.3(ITSN1):c.3017-2A>G	Likely pathogenic
1960283	NM_003024.3(ITSN1):c.725-1G>A	Likely pathogenic
225087	NM_003024.3(ITSN1):c.2227G>T (p.Val743Leu)	Likely pathogenic
2429074	NM_003024.3(ITSN1):c.2772G>A (p.Trp924Ter)	Likely pathogenic
2576126	NM_003024.3(ITSN1):c.3937_3941dup (p.Met1314fs)	Likely pathogenic
3777173	NM_003024.3(ITSN1):c.934C>T (p.Arg312Ter)	Likely pathogenic

SpliceAI

10127 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33649198:T:TA	donor_gain	1.0000
21:33718791:TTACA:T	acceptor_loss	1.0000
21:33718792:TACA:T	acceptor_loss	1.0000
21:33718794:CA:C	acceptor_loss	1.0000
21:33718795:A:AG	acceptor_gain	1.0000
21:33718796:G:GG	acceptor_gain	1.0000
21:33718796:GGC:G	acceptor_gain	1.0000
21:33718854:GTG:G	donor_gain	1.0000
21:33718854:GTGGT:G	donor_loss	1.0000
21:33718855:TGG:T	donor_loss	1.0000
21:33718856:GGT:G	donor_loss	1.0000
21:33718857:GT:G	donor_loss	1.0000
21:33718858:TAAGT:T	donor_loss	1.0000
21:33720206:G:GG	donor_gain	1.0000
21:33721280:G:GG	donor_gain	1.0000
21:33735041:CAG:C	acceptor_loss	1.0000
21:33735043:G:A	acceptor_loss	1.0000
21:33735043:GGGC:G	acceptor_gain	1.0000
21:33735205:G:GA	donor_loss	1.0000
21:33735205:G:GG	donor_gain	1.0000
21:33735206:T:G	donor_loss	1.0000
21:33735458:CAGT:C	donor_gain	1.0000
21:33751209:GAGCA:G	donor_gain	1.0000
21:33751809:GCA:G	acceptor_gain	1.0000
21:33755295:A:AG	acceptor_gain	1.0000
21:33755296:G:GT	acceptor_gain	1.0000
21:33755296:GT:G	acceptor_gain	1.0000
21:33755296:GTGT:G	acceptor_gain	1.0000
21:33767702:C:CA	acceptor_gain	1.0000
21:33767705:A:AG	acceptor_gain	1.0000

AlphaMissense

11292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33735109:T:C	L84P	1.000
21:33755316:T:A	W215R	1.000
21:33755316:T:C	W215R	1.000
21:33755318:G:C	W215C	1.000
21:33755318:G:T	W215C	1.000
21:33755323:T:A	V217D	1.000
21:33755346:T:G	Y225D	1.000
21:33755358:T:C	F229L	1.000
21:33755359:T:C	F229S	1.000
21:33755360:C:A	F229L	1.000
21:33755360:C:G	F229L	1.000
21:33755392:T:C	L240S	1.000
21:33761944:T:A	L249H	1.000
21:33761944:T:C	L249P	1.000
21:33761974:T:C	L259P	1.000
21:33761983:T:A	I262K	1.000
21:33761983:T:G	I262R	1.000
21:33761985:T:A	W263R	1.000
21:33761985:T:C	W263R	1.000
21:33765875:G:C	W263C	1.000
21:33765875:G:T	W263C	1.000
21:33765907:T:A	L274H	1.000
21:33765907:T:C	L274P	1.000
21:33765921:T:C	F279L	1.000
21:33765922:T:C	F279S	1.000
21:33765923:T:A	F279L	1.000
21:33765923:T:G	F279L	1.000
21:33765931:C:A	A282E	1.000
21:33765940:T:C	L285P	1.000
21:33772067:T:G	F350C	1.000

dbSNP variants (sampled 300 via entrez): RS1000006064 (21:33854874 T>G), RS1000036313 (21:33748204 G>A,C), RS1000036662 (21:33725764 C>T), RS1000044022 (21:33896360 C>T), RS1000049574 (21:33829253 G>A), RS1000054339 (21:33658405 G>A), RS1000062374 (21:33731741 C>A,T), RS1000074996 (21:33716938 A>C,G), RS1000094440 (21:33678584 T>G), RS1000099421 (21:33884757 T>G), RS1000106307 (21:33658645 T>C), RS1000137830 (21:33742020 G>A), RS1000138012 (21:33809445 C>T), RS1000152238 (21:33804962 G>A), RS1000158096 (21:33700057 T>A)

Disease associations

OMIM: gene MIM:602442 | disease phenotypes: MIM:189800, MIM:209850, MIM:156200, MIM:189960

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (6): nephrotic syndrome (MONDO:0005377), preeclampsia (MONDO:0005081), neurodevelopmental disorder (MONDO:0700092), autism (MONDO:0005260), intellectual disability, autosomal dominant 1 (MONDO:0007974), esophageal atresia/tracheoesophageal fistula (MONDO:0008586)

Orphanet (3): Preeclampsia (Orphanet:275555), 2q23.1 microdeletion syndrome (Orphanet:228402), Esophageal atresia (Orphanet:1199)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002598_2	Educational attainment	3.000000e-06
GCST003995_25	Tonsillectomy	4.000000e-09
GCST004602_238	Mean corpuscular volume	1.000000e-26
GCST004621_175	Red cell distribution width	7.000000e-26
GCST004630_31	Mean corpuscular hemoglobin	8.000000e-29
GCST005014_121	Tonsillectomy	4.000000e-09
GCST005171_16	QT interval	7.000000e-07
GCST008524_14	Bitter non-alcoholic beverage consumption	5.000000e-07
GCST008839_332	Height	2.000000e-08
GCST90002390_680	Mean corpuscular hemoglobin	8.000000e-78
GCST90002391_173	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST90002392_121	Mean corpuscular volume	4.000000e-74
GCST90002396_73	Mean reticulocyte volume	4.000000e-09
GCST90002397_295	Mean spheric corpuscular volume	2.000000e-26
GCST90002403_536	Red blood cell count	6.000000e-19
GCST90002404_584	Red cell distribution width	5.000000e-66

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0007924	tonsillectomy risk measurement
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004682	QT interval
EFO:0010093	bitter non-alcoholic beverage consumption measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D065886	Neurodevelopmental Disorders	F03.625
D011225	Pre-Eclampsia	C12.050.703.395.249
C531835	Esophageal atresia with or without tracheoesophageal fistula (supp.)
C566947	Mental Retardation, Autosomal Dominant 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523302 (SINGLE PROTEIN), CHEMBL4888458 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

47 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	affects methylation, decreases expression, decreases methylation	3
Aflatoxin B1	decreases expression, increases methylation	3
cobaltous chloride	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
clothianidin	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419732	Binding	Inhibition of GST-tagged human intersectin-1 (1227 to 1571 residues) RhoGEF-catalyzed guanine nucleotide-exchange reaction of human full length Cdc42 (1 to 191 residues) by measuring inhibition of the GDP dissociation from Cdc42 at 0.76 to	Small-molecule inhibitors targeting g-protein-coupled rho guanine nucleotide exchange factors

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
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,
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
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