ARHGAP35

Summary

ARHGAP35 (Rho GTPase activating protein 35, HGNC:4591) is a protein-coding gene on chromosome 19q13.32, encoding Rho GTPase-activating protein 35 (Q9NRY4). Rho GTPase-activating protein (GAP).

The human glucocorticoid receptor DNA binding factor, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The amino acid sequence deduced from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRLF1 enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRLF1 interaction is sequence specific and that transcriptional efficacy of GRLF1 is regulated through its interaction with specific sequence motif. The level of expression is regulated by glucocorticoids.

Source: NCBI Gene 2909 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 173 total — 11 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 9 cancer types
• MANE Select transcript: NM_004491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4591
Approved symbol	ARHGAP35
Name	Rho GTPase activating protein 35
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	GRF-1, p190ARhoGAP, P190A, KIAA1722, p190RhoGAP
Ensembl gene	ENSG00000160007
Ensembl biotype	protein_coding
OMIM	605277
Entrez	2909

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 protein_coding

ENST00000595822, ENST00000596593, ENST00000598548, ENST00000599284, ENST00000672722, ENST00000700035, ENST00000862299

RefSeq mRNA: 1 — MANE Select: NM_004491 NM_004491

CCDS: CCDS46127

Canonical transcript exons

ENST00000672722 — 7 exons

Exon	Start	End
ENSE00001048913	46937264	46937408
ENSE00001217499	46989544	46989675
ENSE00001217506	46987989	46988066
ENSE00001551741	47000331	47005077
ENSE00003610032	46999304	46999409
ENSE00003890769	46860997	46861209
ENSE00003894985	46918488	46922356

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4599 / max 162.8225, expressed in 1747 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176611	6.5132	1677
176607	1.2662	735
176614	0.4801	270
176613	0.4483	200
176610	0.3673	153
176608	0.2812	113
176609	0.0625	19
176619	0.0239	3
176617	0.0102	4
176620	0.0061	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.17	gold quality
endothelial cell	CL:0000115	98.87	gold quality
middle temporal gyrus	UBERON:0002771	98.65	gold quality
postcentral gyrus	UBERON:0002581	98.39	gold quality
entorhinal cortex	UBERON:0002728	98.26	gold quality
parietal lobe	UBERON:0001872	98.21	gold quality
superior vestibular nucleus	UBERON:0007227	97.29	gold quality
substantia nigra pars compacta	UBERON:0001965	97.04	gold quality
left testis	UBERON:0004533	97.04	gold quality
superior frontal gyrus	UBERON:0002661	96.87	gold quality
right testis	UBERON:0004534	96.74	gold quality
pons	UBERON:0000988	96.61	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.49	gold quality
visceral pleura	UBERON:0002401	96.35	gold quality
medial globus pallidus	UBERON:0002477	96.35	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.20	gold quality
seminal vesicle	UBERON:0000998	96.17	gold quality
ventral tegmental area	UBERON:0002691	96.03	gold quality
globus pallidus	UBERON:0001875	95.97	gold quality
corpus epididymis	UBERON:0004359	95.45	gold quality
cortical plate	UBERON:0005343	95.34	gold quality
heart right ventricle	UBERON:0002080	95.28	gold quality
mammary duct	UBERON:0001765	95.25	gold quality
germinal epithelium of ovary	UBERON:0001304	95.13	gold quality
parietal pleura	UBERON:0002400	95.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.06	gold quality
testis	UBERON:0000473	95.04	gold quality
pigmented layer of retina	UBERON:0001782	95.03	gold quality
biceps brachii	UBERON:0001507	94.86	gold quality
dorsal root ganglion	UBERON:0000044	94.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
FOS	Activation
NR3C1
RAP1A
RHOA

miRNA regulators (miRDB)

143 targeting ARHGAP35, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4510	100.00	66.60	2050
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-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6783-3P	99.89	67.92	2059

Literature-anchored findings (GeneRIF, showing 40)

• p190 transiently associates with plexins, and its RhoGAP activity is increased in response to semaphorin stimulation. We conclude that p190-RhoGAP is crucially involved in semaphorin signalling to the actin cytoskeleton, via interaction with plexins. (PMID:16188938)
• FAK-induced down-modulation of RhoA activity via p190RhoGAP is a crucial step in signaling endothelial barrier restoration after increased endothelial permeability (PMID:16308318)
• By linking Rac1 activation and RhoA inhibition, p190 RhoGAP is critical to the protective effects of Ang-1 against endotoxin. (PMID:17562701)
• activation of the RhoA GTPase was defective in VHL(-) cells, and this was possibly mediated by an increased activation of its inhibitor, p190RhoGAP. (PMID:18567581)
• results suggest that co-regulation of Rho activity by p190RhoGAP and ECT2 in the cleavage furrow determines whether cells properly complete cytokinesis (PMID:18642445)
• A previously unknown function of Brk in regulating both RhoA and Ras by phosphorylating p190 and a crucial role of this Brk-elicited signaling pathway in promoting breast malignancy. (PMID:18829532)
• G(alpha)(13)-dependent downstream effects on RhoA activation and invasion tightly depend on cell type-specific GAP activities and that G(alpha)(13)-p190RhoGAP signaling might represent a potential target for intervention in melanoma metastasis. (PMID:18922893)
• p190RhoGAP and p120ctn associated predominantly on the plasma membrane of cells overexpressing E-cadherin, and that E-cadherin-bound p120ctn contributed to RhoA inactivation by favoring p190RhoGAP-RhoA association. (PMID:19293150)
• nmr temperature studies link the ability of p190RhoGAP protein domain FF1 to be phosphorylated with conformational changes in three-dimensional structure. (PMID:19393245)
• Data show that fibroblast, endothelial and carcinoma polarity during cell migration requires FAK and is associated with a complex between FAK, p120RasGAP and p190RhoGAP (p190A), leading to p190A tyrosine phosphorylation. (PMID:19435801)
• Cdh1 formed a physical complex with p190 and stimulated the efficient ubiquitination of p190, both in in vitro and in vivo. (PMID:20530197)
• in addition to activation of RhoGEF(s), reduction of RhoGAP (p190) is a critical mechanism by which increased RhoGTP levels are achieved in late mitosis, thereby ensuring proper cell division. (PMID:20534586)
• A neutrophil- and ss2 integrin-dependent transgenic model of the effector phase of autoimmune arthritis proceeds normally in p190RhoGAP-deficient bone marrow. (PMID:20675588)
• role of the N-terminal region in signaling; Rnd1 and Rnd3 have a KERRA (Lys-Glu-Arg-Arg-Ala) sequence of amino acids in their N-terminus, which functions as the lipid raft-targeting determinant; the sequence mediates lipid raft targeting of p190 RhoGAP correlated with its activation (PMID:22357615)
• These results suggest that folic acid might inhibit endothelial cell migration through inhibiting the RhoA activity mediated by activating the FR/cSrc/p190RhoGAP-signaling pathway. (PMID:23178654)
• RhoA is down-regulated at cell-cell contacts via p190RhoGAP-B in response to tensional homeostasis. (PMID:23552690)
• Overexpression of p190 mRNA associated with lung adenocarcinoma. (PMID:24043274)
• These data suggest that the interaction of human papillomavirus E7 with p190 dysregulates this GTPase activating protein and alters the actin cytoskeleton. (PMID:24403595)
• A ubiquitous binding partner of p190RhoGAP, p120RasGAP (RasGAP), is expressed in much lower levels in DKO4 cells compared to DLD1, and this expression is regulated by KRAS. (PMID:24465899)
• These results place Blk upstream of the p190RhoGAP-RhoA pathway in Galpha13-activated cells, overall representing an opposing signaling module during CXCL12-triggered invasion. (PMID:25025568)
• ARHGAP35 rs1052667 polymorphism was an independent prognostic factor influencing the survival of osteosarcoma. (PMID:25136583)
• GRF-1 expression may modify osteosarcoma prognosis and may be a potential tumor therapeutic target. (PMID:25185653)
• these data demonstrate that a complex of p190RhoGAP-A and anillin modulates RhoA-GTP levels in the cytokinetic furrow to ensure progression of cytokinesis. (PMID:25359885)
• interaction involves the first FF motif of p190A and the winged helix/PCI domain of eIF3A, is enhanced by serum stimulation and reduced by phosphatase treatment (PMID:28007963)
• results indicate that inactivating mutation of ARHGAP35 in the repeat is rare in colorectal cancer (CRC) with MSI and suggest that ARHGAP35 inactivating mutation may not play an important role in CRC development (PMID:28176259)
• report association of APOE and TOMM40 with behavioural variant frontotemporal dementia, and ARHGAP35 and SERPINA1 with progressive non-fluent aphasia. (PMID:28387812)
• our data identify an unappreciated connection between p190RhoGAP and the proteins that control spindle poles including Aurora A kinase and Eg5 that is required to prevent or correct spindle pole fragmentation. (PMID:29656322)
• The data reveal a novel mechanism consistent with a tumor-suppressor function for ARHGAP35. (PMID:29934311)
• High ARHGAP35 expression is associated with lung adenocarcinoma. (PMID:30015929)
• Tau regulates the microtubule-dependent migration of glioblastoma cells via the Rho-ROCK signaling pathway. (PMID:30659115)
• TRIM65 mediates ubiquitination of ARHGAP35, whose degradation leads to elevated Rho GTPase activity and colorectal cancer metastasis. (PMID:31332286)
• p190A inactivating mutations cause aberrant RhoA activation and promote malignant transformation via the Hippo-YAP pathway in endometrial cancer. (PMID:32457342)
• p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth. (PMID:32641858)
• Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signaling. (PMID:32663194)
• Rho GTPase-activating protein 35 suppresses gastric cancer metastasis by regulating cytoskeleton reorganization and epithelial-to-mesenchymal transition. (PMID:35758029)
• The p190 RhoGAPs, ARHGAP35, and ARHGAP5 are implicated in GnRH neuronal development: Evidence from patients with idiopathic hypogonadotropic hypogonadism, zebrafish, and in vitro GAP activity assay. (PMID:36178483)
• Tumor-derived ARHGAP35 mutations enhance the Galpha13-Rho signaling axis in human endometrial cancer. (PMID:36257976)
• ARHGAP35 is a novel factor disrupted in human developmental eye phenotypes. (PMID:36450800)
• Identification of an inhibitory domain in GTPase-activating protein p190RhoGAP responsible for masking its functional GAP domain. (PMID:36516886)
• Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1. (PMID:37507023)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap35a	ENSDARG00000062577
mus_musculus	Arhgap35	ENSMUSG00000058230
rattus_norvegicus	Arhgap35	ENSRNOG00000015852

Paralogs (4): SYDE2 (ENSG00000097096), SYDE1 (ENSG00000105137), CHN2 (ENSG00000106069), CHN1 (ENSG00000128656)

Protein

Protein identifiers

Rho GTPase-activating protein 35 — Q9NRY4 (reviewed: Q9NRY4)

Alternative names: Glucocorticoid receptor DNA-binding factor 1, Glucocorticoid receptor repression factor 1, Rho GAP p190A

All UniProt accessions (1): Q9NRY4

UniProt curated annotations — full annotation on UniProt →

Function. Rho GTPase-activating protein (GAP). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity. This binding is inhibited by phosphorylation by PRKCA. Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis. Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation. Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation. During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth. Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5’-GAGAAAAGAAACTGGAGAAACTC-3’; this function is however unclear and would need additional experimental evidences.

Subunit / interactions. Interacts with RASA1. Interacts with the general transcription factor GTF2I, the interaction sequesters GTF2I in the cytoplasm.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Nucleus. Cell membrane.

Tissue specificity. Detected in neutrophils (at protein level).

Post-translational modifications. Phosphorylation of Tyr-1105 by PTK6 promotes the association with RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-308 by PDGFRA inhibits binding to GTF2I. Phosphorylated by PRKCA at Ser-1221 and Thr-1226, induces relocalization from the cytoplasm to regions of plasma membrane ruffling and prevents the binding and substrate specificity regulation by phospholipids. In brain, phosphorylated by FYN and SRC. During focal adhesion formation, phosphorylated by MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3 inhibits GAP function and localizes ARGHAP35 away from newly forming focal adhesions and stress fibers in cells spreading on fibronectin. Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by MAPK and inhibits RhoGAP activity and modulates polarized cell migration.

Activity regulation. Binding of acidic phospholipids inhibits the Rho GAP activity and promotes the Rac GAP activity.

Domain organisation. N-terminal part (1-266) has GTPase activity. Required for proper cellular localization. The pG1 pseudoGTPase domain does not bind GTP.

RefSeq proteins (1): NP_004482* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001806	Small_GTPase	Family
IPR002713	FF_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032835	RhoGAP-FF1	Domain
IPR036517	FF_domain_sf	Homologous_superfamily
IPR039006	RhoGAP_pG2	Domain
IPR039007	pG1	Domain
IPR045786	RhoGAP_pG1_pG2	Domain
IPR051978	Rho-GAP_domain	Family
IPR057284	FF_RHG35_4th	Domain

Pfam: PF00071, PF00620, PF16512, PF19518, PF23083

UniProt features (110 total): helix 28, modified residue 23, strand 13, sequence conflict 8, domain 7, binding site 7, turn 7, region of interest 6, mutagenesis site 5, compositionally biased region 4, chain 1, site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6WAY	X-RAY DIFFRACTION	1.5
6PXC	X-RAY DIFFRACTION	1.6
3C5H	X-RAY DIFFRACTION	1.8
8DGQ	X-RAY DIFFRACTION	1.95
3FK2	X-RAY DIFFRACTION	2.8
2K85	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRY4-F1	74.08	0.43

Functional residue map

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

Catalytic / active sites (1): 1284 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Ligand- & substrate-binding residues (7): 28; 33–37; 52; 56; 95–97; 201–203; 229–231

Post-translational modifications (23): 308, 589, 770, 773, 970, 975, 985, 1001, 1072, 1087, 1105, 1134, 1142, 1150, 1176, 1179, 1221, 1226, 1236, 1472 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
1221	no effect on total phosphorylation levels. abolishes inhibition of phospholipid binding by prkca phosphorylation. decrea
1221	enhances rac gap activity.
1226	no effect on total phosphorylation levels. abolishes inhibition of phospholipid binding by prkca phosphorylation. decrea
1226	enhances rac gap activity.
1236	no effect on total phosphorylation levels. no effect on inhibition of phospholipid binding by prkca phosphorylation. abo

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-416550	Sema4D mediated inhibition of cell attachment and migration
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 286 (showing top): PID_SHP2_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEURON_RECOGNITION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (23): neural tube closure (GO:0001843), Rho protein signal transduction (GO:0007266), axon guidance (GO:0007411), axonal fasciculation (GO:0007413), regulation of actin polymerization or depolymerization (GO:0008064), regulation of cell shape (GO:0008360), regulation of cell size (GO:0008361), positive regulation of neuron projection development (GO:0010976), cell migration (GO:0016477), central nervous system neuron axonogenesis (GO:0021955), mammary gland development (GO:0030879), forebrain development (GO:0030900), establishment or maintenance of actin cytoskeleton polarity (GO:0030950), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of Rho protein signal transduction (GO:0035024), camera-type eye development (GO:0043010), negative regulation of vascular permeability (GO:0043116), wound healing, spreading of cells (GO:0044319), positive regulation of cilium assembly (GO:0045724), regulation of axonogenesis (GO:0050770), regulation of small GTPase mediated signal transduction (GO:0051056), neuron projection guidance (GO:0097485), signal transduction (GO:0007165)

GO Molecular Function (7): DNA binding (GO:0003677), GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), GTP binding (GO:0005525), phospholipid binding (GO:0005543), nucleotide binding (GO:0000166), lipid binding (GO:0008289)

GO Cellular Component (9): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	14
Sema4D in semaphorin signaling	1
Signaling by PTK6	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
axonogenesis	3
regulation of neuron projection development	2
actin cytoskeleton organization	2
primary neural tube formation	1
tube closure	1
small GTPase-mediated signal transduction	1
neuron projection guidance	1
neuron recognition	1
axon development	1
neuron projection fasciculation	1
actin polymerization or depolymerization	1
regulation of actin filament length	1
regulation of actin filament organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of cellular component size	1
neuron projection development	1
positive regulation of cell projection organization	1
cell motility	1
central nervous system neuron development	1
gland development	1
brain development	1
anatomical structure development	1
establishment or maintenance of cytoskeleton polarity	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
eye development	1
regulation of vascular permeability	1
cell migration	1
epiboly involved in wound healing	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
regulation of anatomical structure morphogenesis	1
nucleic acid binding	1

Protein interactions and networks

STRING

1490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP35	RASA1	P20936	993
ARHGAP35	RND3	P52199	952
ARHGAP35	CTNND1	O60716	943
ARHGAP35	RHOA	P06749	922
ARHGAP35	RND1	Q92730	879
ARHGAP35	GTF2I	P78347	829
ARHGAP35	RND2	P52198	810
ARHGAP35	WASL	O00401	742
ARHGAP35	HCLS1	P14317	739
ARHGAP35	CFL2	Q9Y281	735
ARHGAP35	RHOC	P08134	731
ARHGAP35	CTTN	Q14247	725
ARHGAP35	CFL1	P23528	724
ARHGAP35	CDH17	Q12864	714
ARHGAP35	PTK2	Q05397	704

IntAct

33 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
RND1	ARHGAP35	psi-mi:“MI:0915”(physical association)	0.400
ARHGAP35	CDC42	psi-mi:“MI:0915”(physical association)	0.370
E7	AP2A1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
SERPINB2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
ARHGAP35	CSTB	psi-mi:“MI:0914”(association)	0.350
Arhgap28	EZR	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ARHGAP35	RASA1	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
HSPA12B	VWA8	psi-mi:“MI:0914”(association)	0.350
HSPA12A	ARHGEF10	psi-mi:“MI:0914”(association)	0.350
PLEKHA2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
FAM167A	IFT56	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
KLHL14	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
SF3B3	MYO9A	psi-mi:“MI:0914”(association)	0.350
DNAJA2	QSOX1	psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
EZR	PLS3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (126): KRT31 (Two-hybrid), TCERG1 (Co-fractionation), ARHGAP35 (Affinity Capture-MS), RHOA (Reconstituted Complex), CDC42 (Reconstituted Complex), RAC1 (Reconstituted Complex), ARHGAP35 (Affinity Capture-MS), ARHGAP35 (Affinity Capture-RNA), ARHGAP35 (Affinity Capture-MS), ARHGAP35 (Affinity Capture-MS), ARHGAP35 (Reconstituted Complex), ARHGAP35 (Proximity Label-MS), ARHGAP35 (Negative Genetic), ARHGAP35 (Affinity Capture-RNA), ARHGAP35 (Proximity Label-MS)

ESM2 similar proteins: A6NFE3, B3LF48, C7A639, F1SSF9, I2DDG2, O13728, P02635, P02636, P05946, P08733, P14202, P32070, P45961, P81128, P83509, P97393, Q01449, Q02045, Q13017, Q3SZE5, Q3T064, Q4KLL5, Q4R6C5, Q4V7T8, Q52K82, Q54MF3, Q5E9G1, Q5R629, Q66IC9, Q6AXZ3, Q6DCF6, Q6DJ05, Q6NU25, Q803V3, Q91YM2, Q94CF0, Q969Q6, Q96C74, Q9BZX4, Q9D581

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ROCK1	down-regulates	ARHGAP35	phosphorylation
ARHGAP35	“down-regulates activity”	RHOA	“gtpase-activating protein”
ARHGAP35	“down-regulates activity”	RAC1	“gtpase-activating protein”
TRIM65	“down-regulates quantity by destabilization”	ARHGAP35	polyubiquitination
SRC	up-regulates	ARHGAP35	phosphorylation
PTPRZ1	“down-regulates activity”	ARHGAP35	dephosphorylation
ROCK1	“down-regulates activity”	ARHGAP35	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 9 cancer types — AML, BCC, BLCA, BRCA, CCRCC, LUSC, OVT, UCEC, UTUC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	10
Uncertain significance	130
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1727215	NM_004491.5(ARHGAP35):c.4251del (p.Thr1418fs)	Pathogenic
1727216	NM_004491.5(ARHGAP35):c.4444del (p.Gln1482fs)	Pathogenic
1727217	NM_004491.5(ARHGAP35):c.1849C>T (p.Arg617Ter)	Pathogenic
2500753	NM_004491.5(ARHGAP35):c.2814dup (p.Lys939Ter)	Pathogenic
4136810	NM_004491.5(ARHGAP35):c.3199C>T (p.Gln1067Ter)	Pathogenic
4642410	NM_004491.5(ARHGAP35):c.883_890delinsATCAACC (p.Val295fs)	Pathogenic
4642420	NM_004491.5(ARHGAP35):c.1233_1242delinsGC (p.Ala412fs)	Pathogenic
4830228	NM_004491.5(ARHGAP35):c.2118_2119del (p.Gly707fs)	Pathogenic
4830628	NM_004491.5(ARHGAP35):c.2835_2836del (p.Asn946fs)	Pathogenic
4831221	NM_004491.5(ARHGAP35):c.875G>A (p.Trp292Ter)	Pathogenic
4838826	NM_004491.5(ARHGAP35):c.4054C>T (p.Gln1352Ter)	Pathogenic
1679908	NM_004491.5(ARHGAP35):c.2565C>A (p.Tyr855Ter)	Likely pathogenic
1679909	NM_004491.5(ARHGAP35):c.3283_3286delinsT (p.Val1095_Lys1096delinsTer)	Likely pathogenic
1679913	NM_004491.5(ARHGAP35):c.3569_3570del (p.Glu1190fs)	Likely pathogenic
1679920	NM_004491.5(ARHGAP35):c.325C>T (p.Arg109Ter)	Likely pathogenic
1679921	NM_004491.5(ARHGAP35):c.345del (p.Tyr116fs)	Likely pathogenic
1679922	NM_004491.5(ARHGAP35):c.352A>T (p.Lys118Ter)	Likely pathogenic
1679923	NM_004491.5(ARHGAP35):c.516del (p.Asn173fs)	Likely pathogenic
1679924	NM_004491.5(ARHGAP35):c.1800_1803del (p.Val601fs)	Likely pathogenic
1699373	NM_004491.5(ARHGAP35):c.1600C>T (p.Gln534Ter)	Likely pathogenic
393971	GRCh37/hg19 19q13.32(chr19:47450549-47880338)x3	Likely pathogenic

SpliceAI

1346 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46937257:T:A	acceptor_gain	1.0000
19:46937258:G:A	acceptor_gain	1.0000
19:46945380:G:GT	donor_gain	1.0000
19:46987987:A:AG	acceptor_gain	1.0000
19:46987987:AGGAC:A	acceptor_loss	1.0000
19:46987988:G:GG	acceptor_gain	1.0000
19:46987988:GGACT:G	acceptor_gain	1.0000
19:46989671:ACACA:A	donor_gain	1.0000
19:46989672:CACA:C	donor_gain	1.0000
19:46989673:ACA:A	donor_gain	1.0000
19:46989673:ACAG:A	donor_loss	1.0000
19:46989674:CA:C	donor_gain	1.0000
19:46989674:CAG:C	donor_loss	1.0000
19:46989675:AGT:A	donor_loss	1.0000
19:46989676:G:GG	donor_gain	1.0000
19:46989676:GTG:G	donor_loss	1.0000
19:46989677:TGA:T	donor_loss	1.0000
19:46989678:GAG:G	donor_loss	1.0000
19:46989679:AGTAC:A	donor_loss	1.0000
19:46999298:CCTCA:C	acceptor_loss	1.0000
19:46999299:CTCAG:C	acceptor_loss	1.0000
19:46999300:TCAGA:T	acceptor_loss	1.0000
19:46999301:CAG:C	acceptor_loss	1.0000
19:46999302:A:AG	acceptor_gain	1.0000
19:46999302:AGAAA:A	acceptor_loss	1.0000
19:46999303:G:GA	acceptor_gain	1.0000
19:46999303:G:GT	acceptor_loss	1.0000
19:46999303:GA:G	acceptor_gain	1.0000
19:46999303:GAA:G	acceptor_gain	1.0000
19:46999386:G:GG	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015476 (19:46937585 T>A), RS1000042863 (19:46981028 G>A), RS1000095943 (19:46985134 A>G), RS1000136316 (19:46987166 C>T), RS1000139346 (19:46880002 C>G), RS1000171692 (19:46879865 C>A,T), RS1000172225 (19:46974652 G>A), RS1000173641 (19:47004797 G>A), RS1000195072 (19:46923431 T>A,C), RS1000208054 (19:46883177 C>T), RS1000225799 (19:47005080 TGA>T), RS1000297345 (19:46943551 G>A), RS1000302725 (19:46882886 G>C), RS1000327399 (19:46929600 T>TG), RS1000333306 (19:46993313 G>C)

Disease associations

OMIM: gene MIM:605277 | disease phenotypes: MIM:212720, MIM:604229, MIM:309800

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	Autosomal dominant
congenital hypogonadotropic hypogonadism	Strong	Autosomal dominant
developmental defect of the eye	Strong	Autosomal dominant
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (9): Martsolf syndrome 1 (MONDO:8000008), neurodevelopmental disorder (MONDO:0700092), Peters anomaly (MONDO:0011414), syndromic microphthalmia (MONDO:0016073), breast ductal adenocarcinoma (MONDO:0005590), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), complex neurodevelopmental disorder (MONDO:0100038), congenital hypogonadotropic hypogonadism (MONDO:0015770), (MONDO:0020145)

Orphanet (3): Cataract-intellectual disability-hypogonadism syndrome (Orphanet:1387), Peters anomaly (Orphanet:708), Syndromic microphthalmia-anophthalmia-coloboma (Orphanet:202948)

HPO phenotypes

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

HPO	Term
HP:0000659	Peters anomaly

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001201_11	Response to platinum-based chemotherapy (cisplatin)	7.000000e-06
GCST010703_65	Brain morphology (MOSTest)	2.000000e-08
GCST010727_43	Deep white matter hyperintensities	9.000000e-06
GCST011351_23	Aspartate aminotransferase levels	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D065886	Neurodevelopmental Disorders	F03.625
C536028	Martsolf syndrome (supp.)
C537884	Peters anomaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523646 (PROTEIN COMPLEX)

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

Binding affinities (BindingDB)

9 measured of 10 human assays (10 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	EC50	1.05 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] 2-phenylacetate	EC50	2.85 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
(1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one	EC50	2.9 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
Hydrocortisone Butyrate	EC50	2.94 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] propanoate	EC50	3.17 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] heptanoate	EC50	5.27 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] hexanoate	EC50	5.68 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] benzoate	EC50	7.46 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives
[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] 2-methylpropanoate	EC50	15.6 nM	US-10188667: Pharmaceutical compositions and methods of use of 4-pregenen-11β-17-21-triol-3,20-dione derivatives

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium	decreases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
AG 1879	decreases reaction, increases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Atrazine	increases expression	1
Azacitidine	increases expression	1
Caffeine	affects phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1
Folic Acid	decreases reaction, increases activity, affects reaction, decreases activity	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419748	Binding	Inhibition of human p190 expressed in mouse NIH/3T3 cells assessed as reduction in human full length RhoA (1 to 193 residues) interaction with p190 at 50 to 100 uM incubated for 1 hr by Western blot analysis based His-RhoA pull-down assay	Small-molecule inhibitors targeting g-protein-coupled rho guanine nucleotide exchange factors

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders