ARHGAP32

Summary

ARHGAP32 (Rho GTPase activating protein 32, HGNC:17399) is a protein-coding gene on chromosome 11q24.3, encoding Rho GTPase-activating protein 32 (A7KAX9). GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases.

RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).

Source: NCBI Gene 9743 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 352 total — 2 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001378024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17399
Approved symbol	ARHGAP32
Name	Rho GTPase activating protein 32
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	GRIT, KIAA0712, MGC1892, RICS, GC-GAP
Ensembl gene	ENSG00000134909
Ensembl biotype	protein_coding
OMIM	608541
Entrez	9743

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 retained_intron

ENST00000310343, ENST00000392657, ENST00000524655, ENST00000525234, ENST00000526162, ENST00000527272, ENST00000533509, ENST00000534357, ENST00000682385

RefSeq mRNA: 4 — MANE Select: NM_001378024 NM_001142685, NM_001378024, NM_001378025, NM_014715

CCDS: CCDS31718, CCDS44769, CCDS91623

Canonical transcript exons

ENST00000682385 — 23 exons

Exon	Start	End
ENSE00001352689	128972453	128973432
ENSE00001381102	128974124	128975002
ENSE00002153866	128965060	128971159
ENSE00002181090	129123888	129123929
ENSE00002454217	129124803	129124894
ENSE00002496377	129093621	129093707
ENSE00002517509	129123446	129123530
ENSE00002533020	129066731	129066868
ENSE00003473107	128998319	128998468
ENSE00003476613	128980553	128980748
ENSE00003484173	128981416	128981561
ENSE00003511919	128986524	128986668
ENSE00003512882	129063902	129064024
ENSE00003522366	129040928	129041009
ENSE00003534854	129062280	129062357
ENSE00003558110	128976563	128976634
ENSE00003558736	129064841	129064933
ENSE00003613743	129164319	129164427
ENSE00003615924	128988023	128988125
ENSE00003646194	128986003	128986085
ENSE00003684916	128981829	128981936
ENSE00003689162	128978770	128978915
ENSE00003918801	129192083	129192325

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6700 / max 459.3157, expressed in 1492 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123138	2.7161	943
123127	2.3234	309
123126	1.5962	286
123137	1.5589	884
123135	0.7309	362
123130	0.6264	132
123136	0.4742	244
123134	0.4558	242
123125	0.1075	51
123129	0.0475	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	97.02	gold quality
secondary oocyte	CL:0000655	95.86	gold quality
postcentral gyrus	UBERON:0002581	95.56	gold quality
endothelial cell	CL:0000115	95.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.99	gold quality
parietal lobe	UBERON:0001872	94.78	gold quality
superior frontal gyrus	UBERON:0002661	94.25	gold quality
primary visual cortex	UBERON:0002436	94.18	gold quality
occipital lobe	UBERON:0002021	93.82	gold quality
entorhinal cortex	UBERON:0002728	92.77	gold quality
esophagus squamous epithelium	UBERON:0006920	92.50	gold quality
sural nerve	UBERON:0015488	91.57	gold quality
palpebral conjunctiva	UBERON:0001812	91.47	gold quality
duodenum	UBERON:0002114	90.22	gold quality
epithelium of esophagus	UBERON:0001976	89.87	gold quality
squamous epithelium	UBERON:0006914	89.83	gold quality
oocyte	CL:0000023	89.69	gold quality
lower esophagus mucosa	UBERON:0035834	89.66	gold quality
gingival epithelium	UBERON:0001949	89.55	gold quality
prefrontal cortex	UBERON:0000451	89.44	gold quality
buccal mucosa cell	CL:0002336	89.03	gold quality
esophagus mucosa	UBERON:0002469	88.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.72	gold quality
oviduct epithelium	UBERON:0004804	88.58	gold quality
frontal cortex	UBERON:0001870	88.55	gold quality
cortical plate	UBERON:0005343	88.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.37	gold quality
pancreatic ductal cell	CL:0002079	88.37	silver quality
mucosa of sigmoid colon	UBERON:0004993	88.11	gold quality
neocortex	UBERON:0001950	87.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.98
E-MTAB-6058	no	129.80
E-GEOD-100618	no	103.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1

miRNA regulators (miRDB)

177 targeting ARHGAP32, 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-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 16)

• These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases. (PMID:12446789)
• involvement in the regulation of neurite outgrowth by exerting its RhoGAP activity and that its cellular activity may be regulated through interaction with Src-like tyrosine kinases (PMID:12454018)
• This article analyzes Rac activation during live neutrophil chemotaxis. (PMID:12477392)
• RICS may regulate dendritic spine morphology and strength by modulating Rho GTPases (PMID:12531901)
• is phosphorylated by Fyn in oligodendrocytes (PMID:12788081)
• GC-GAP may play a role in dendritic morphogenesis and also possibly in neural/glial cell proliferation (PMID:12819203)
• p250GAP is likely to be involved in actin reorganization in dendritic spines (PMID:12857875)
• p250GAP may be involved in NMDA receptor activity-dependent actin reorganization in dendritic spines (PMID:12857875)
• Results suggest that a splice variant of RICS, PX-RICS, is involved in early brain development including extension of axons and dendrites, and postnatal remodeling and fine-tuning of neural circuits. (PMID:17663722)
• Results suggest that PX-RICS ensures the efficient entry of the N-cadherin/beta-catenin complex into the secretory pathway, and thereby regulates the amount of N-cadherin available for cell adhesion and FGFR4-mediated signaling. (PMID:18451111)
• miR132-p250GAP pathway plays a key role in activity-dependent structural and functional plasticity. (PMID:18577589)
• The PX-RICS-14-3-3zeta/theta complex couples N-cadherin-beta-catenin with dynein-dynactin to mediate its export from the endoplasmic reticulum. (PMID:20308060)
• the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia. (PMID:22530067)
• Cdh1-APC together with the RhoA regulators p250GAP and Smurf1 controls axon growth in the mammalian brain (PMID:23226367)
• Circ_ARHGAP32 acts as miR-665 sponge to upregulate FGF2 to promote ox-LDL induced vascular smooth muscle cells proliferation and migration. (PMID:35662113)
• Association between Grit and depressive symptoms at the timing of job start among medical residents during the COVID-19 pandemic in Japan: a cross-sectional study. (PMID:37343594)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap32b	ENSDARG00000074184
danio_rerio	arhgap32a	ENSDARG00000075334
mus_musculus	Arhgap32	ENSMUSG00000041444
rattus_norvegicus	Arhgap32	ENSRNOG00000008709
drosophila_melanogaster	CdGAPr	FBGN0032821
caenorhabditis_elegans		WBGENE00009800

Paralogs (3): ARHGAP33 (ENSG00000004777), ARHGAP31 (ENSG00000031081), ARHGAP30 (ENSG00000186517)

Protein

Protein identifiers

Rho GTPase-activating protein 32 — A7KAX9 (reviewed: A7KAX9)

Alternative names: Brain-specific Rho GTPase-activating protein, GAB-associated Cdc42/Rac GTPase-activating protein, GC-GAP, GTPase regulator interacting with TrkA, Rho-type GTPase-activating protein 32, Rho/Cdc42/Rac GTPase-activating protein RICS, RhoGAP involved in the beta-catenin-N-cadherin and NMDA receptor signaling, p200RhoGAP, p250GAP

All UniProt accessions (4): A0A804HK06, A7KAX9, E9PRH3, G3V174

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity.

Subunit / interactions. Interacts with NTRK1 (via cytoplasmic domain); the interaction is independent of the phosphorylation state of NTRK1. Interacts with SHC3 (via SH2 domain). Interacts with RASA1 (via SH3 domain); the interaction is necessary for the Ras activation and cell transforming activities of ARHGAP32. Interacts with GAB1 and GAB2. Interacts with CRK and CRKL. Found in a complex with CRKL and BCAR1; upon EGF stimulation BCAR1 may be replaced by EGFR. Interacts with NCK1 (via SH3 domain); NCK1 recruits phosphorylated BCAR1 to the complex. Isoform 2 interacts with FYN; the interaction appears to be dependent on tyrosine phosphorylation of ARHGAP32. Interacts with EGFR; the interaction requires EGF stimulation and is increased by SHC3. Interacts with CDC42; the interaction requires constitutively active CDC42. Interacts with CTNNB1. Interacts with GRIN2B. Interacts with DLG4 and CDH2. Interacts with GPHN.

Subcellular location. Postsynaptic density. Cell projection. Dendritic spine. Cytoplasm. Cell cortex. Endosome membrane. Golgi apparatus membrane. Endoplasmic reticulum membrane. Membrane.

Tissue specificity. Isoform 1 and isoform 2 are highly expressed in brain and testis. Isoform 1 is also expressed in other tissues such as lung, liver and spleen.

Post-translational modifications. Isoform 2 is phosphorylated on multiple tyrosine residues by FYN. Phosphorylated tyrosine residues undergo dephosphorylation after stimulation of NMDA receptors. Phosphorylated in vitro by CaMK2 in the presence of calmodulin and calcium; which inhibits GAP activity.

Domain organisation. The N-terminal PX domain interacts specifically with phosphatidylinositides.

Similarity. Belongs to the PX domain-containing GAP family.

Isoforms (3)

UniProt ID	Names	Canonical?
A7KAX9-1	1, PX-RICS	yes
A7KAX9-2	2
A7KAX9-3	3

RefSeq proteins (4): NP_001136157, NP_001364953, NP_001364954, NP_055530 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001452	SH3_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR042139	PX_ARHGAP32	Domain
IPR051576	PX-Rho_GAP	Family

Pfam: PF00620, PF14604

UniProt features (61 total): modified residue 13, compositionally biased region 12, helix 11, region of interest 7, mutagenesis site 5, splice variant 4, domain 3, turn 3, chain 1, site 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3IUG	X-RAY DIFFRACTION	1.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A7KAX9-F1	43.67	0.12

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): 407 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (13): 706, 709, 732, 738, 852, 856, 892, 952, 1203, 1523, 1533, 1585, 2037

Mutagenesis-validated functional residues (5):

Position	Phenotype
173	loss of binding to phospholipids. cytoplasmic localization.
407	mild effect on gap activity and neurite-promotion upon nerve growth factor stimulation.
407	loss of gap activity.
407	loss of gap activity. in isoform 1, no inhibitory effect on neurite extension.
447	loss of gap activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
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-9035034	RHOF GTPase cycle
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 242 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_SYNAPSE_ASSEMBLY, JAEGER_METASTASIS_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, AREB6_01, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (3): small GTPase-mediated signal transduction (GO:0007264), regulation of small GTPase mediated signal transduction (GO:0051056), signal transduction (GO:0007165)

GO Molecular Function (4): GTPase activator activity (GO:0005096), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515), phosphatidylinositol binding (GO:0035091)

GO Cellular Component (18): Golgi membrane (GO:0000139), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cell cortex (GO:0005938), endosome membrane (GO:0010008), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), dendritic spine (GO:0043197), cytoplasm (GO:0005737), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	12
Regulation of CDH1 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cytoplasm	4
endomembrane system	3
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
phospholipid binding	1
binding	1
anion binding	1
Golgi apparatus	1
nucleolus	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
asymmetric synapse	1
postsynaptic specialization	1
cytoskeleton	1
dendrite	1
neuron spine	1
postsynapse	1
intracellular anatomical structure	1
cytoplasmic vesicle	1
vacuole	1
plasma membrane	1
cell junction	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP32	RASA1	P20936	785
ARHGAP32	SYNGAP1	Q96PV0	650
ARHGAP32	CDC42	P21181	591
ARHGAP32	BDNF	P23560	587
ARHGAP32	CRK	P46108	582
ARHGAP32	RHOA	P06749	579
ARHGAP32	DLG4	P78352	556
ARHGAP32	CRKL	P46109	530
ARHGAP32	A1BG	P04217	511
ARHGAP32	LIMK1	P53667	510
ARHGAP32	MECP2	P51608	508
ARHGAP32	CDH2	P19022	502
ARHGAP32	SUCO	Q9UBS9	497
ARHGAP32	SLITRK1	Q96PX8	496
ARHGAP32	GABARAP	O95166	494

IntAct

107 interactions, top by confidence:

A	B	Type	Score
ARHGAP32	ABI2	psi-mi:“MI:0915”(physical association)	0.670
ABI2	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
ARHGAP32	FYN	psi-mi:“MI:0915”(physical association)	0.630
FYN	ARHGAP32	psi-mi:“MI:0407”(direct interaction)	0.630
FYN	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
CRK	ARHGAP32	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
NCK2	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	TLE5	psi-mi:“MI:0915”(physical association)	0.560
DZIP3	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	MDFI	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.560
MDFI	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	DZIP3	psi-mi:“MI:0915”(physical association)	0.560
TLE5	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	LHX2	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP32	SFN	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (196): ARHGAP32 (Two-hybrid), ARHGAP32 (Two-hybrid), ARHGAP32 (Two-hybrid), ARHGAP32 (Two-hybrid), ABI2 (Two-hybrid), LZTS2 (Two-hybrid), ARHGAP32 (Affinity Capture-RNA), ARHGAP32 (Affinity Capture-MS), RAC1 (Biochemical Activity), EGFR (Affinity Capture-Western), SHC1 (Affinity Capture-Western), ARHGAP32 (Affinity Capture-MS), ARHGAP32 (Affinity Capture-MS), ARHGAP32 (Affinity Capture-MS), ARHGAP32 (Affinity Capture-MS)

ESM2 similar proteins: A0A078CGE6, A2QHV0, A7KAX9, A7SNN5, A9RVK2, B0XPE7, B5X564, D0Z5N4, F4HYG2, F4I114, F4IRW0, F4J394, F4J6F6, F4JY37, O00444, O13839, O24527, O43065, P0CP71, P13185, P38623, P42858, P50526, Q03407, Q0CL79, Q0WPH8, Q14693, Q19192, Q2KHT3, Q2QAV0, Q4WJI7, Q5B4Z3, Q5R9Z7, Q60DG4, Q6GPD0, Q6H647, Q756Z0, Q75CH3, Q75DK7, Q75QN6

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

3 interactions.

A	Effect	B	Mechanism
GAB1	up-regulates	ARHGAP32	relocalization
GAB2	up-regulates	ARHGAP32	relocalization
NTRK1	up-regulates	ARHGAP32	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Activation of BAD and translocation to mitochondria	7	87.4×	1e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	77.1×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	77.1×	2e-10
Activation of BH3-only proteins	7	57.0×	2e-09
Signaling by RAS mutants	6	41.6×	2e-07
RHO GTPases activate PKNs	7	36.4×	4e-08
Intrinsic Pathway for Apoptosis	7	33.6×	6e-08
Prefoldin mediated transfer of substrate to CCT/TriC	5	32.3×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	28.7×	2e-05
protein targeting	5	25.4×	2e-04
substantia nigra development	5	25.4×	2e-04
cell surface receptor protein tyrosine kinase signaling pathway	8	19.3×	6e-06
epidermal growth factor receptor signaling pathway	5	17.2×	1e-03
cerebral cortex development	5	14.3×	2e-03
positive regulation of cell growth	5	12.7×	2e-03
intracellular protein localization	8	11.6×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	269
Likely benign	41
Benign	16

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4813608	NM_001378024.1(ARHGAP32):c.1583C>G (p.Thr528Arg)	Pathogenic
57257	GRCh38/hg38 11q24.2-24.3(chr11:125891315-129072391)x1	Pathogenic
442187	GRCh37/hg19 11q24.3(chr11:128047942-129015375)x1	Likely pathogenic
4532277	NM_001378024.1(ARHGAP32):c.610C>T (p.Arg204Ter)	Likely pathogenic

SpliceAI

4660 predictions. Top by Δscore:

Variant	Effect	Δscore
11:128974999:TCAC:T	acceptor_gain	1.0000
11:128975000:CAC:C	acceptor_gain	1.0000
11:128975000:CACC:C	acceptor_gain	1.0000
11:128975001:ACC:A	acceptor_loss	1.0000
11:128975003:C:CA	acceptor_loss	1.0000
11:128975003:C:CC	acceptor_gain	1.0000
11:128975004:T:A	acceptor_loss	1.0000
11:128975012:A:C	acceptor_gain	1.0000
11:128976559:TTA:T	donor_loss	1.0000
11:128976560:TA:T	donor_loss	1.0000
11:128976561:A:AC	donor_gain	1.0000
11:128976562:C:CC	donor_gain	1.0000
11:128976562:CCAT:C	donor_gain	1.0000
11:128976631:CCAC:C	acceptor_gain	1.0000
11:128976632:CAC:C	acceptor_gain	1.0000
11:128976632:CACC:C	acceptor_gain	1.0000
11:128976635:C:CC	acceptor_gain	1.0000
11:128978767:CACC:C	donor_loss	1.0000
11:128978768:A:AC	donor_gain	1.0000
11:128978768:AC:A	donor_gain	1.0000
11:128978769:C:CA	donor_gain	1.0000
11:128978769:CC:C	donor_gain	1.0000
11:128978769:CCT:C	donor_gain	1.0000
11:128978769:CCTT:C	donor_gain	1.0000
11:128978769:CCTTT:C	donor_gain	1.0000
11:128978912:CTTT:C	acceptor_gain	1.0000
11:128978913:TTT:T	acceptor_gain	1.0000
11:128978914:TT:T	acceptor_gain	1.0000
11:128978914:TTC:T	acceptor_loss	1.0000
11:128978915:TCTAT:T	acceptor_loss	1.0000

AlphaMissense

13776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:128978870:C:A	W660C	1.000
11:128978870:C:G	W660C	1.000
11:128978872:A:G	W660R	1.000
11:128978872:A:T	W660R	1.000
11:128981475:A:G	L560P	1.000
11:128981480:G:C	F558L	1.000
11:128981480:G:T	F558L	1.000
11:128981481:A:G	F558S	1.000
11:128981482:A:G	F558L	1.000
11:128981487:A:T	V556D	1.000
11:128981490:A:T	V555D	1.000
11:128981497:A:G	S553P	1.000
11:128981512:C:T	E548K	1.000
11:128981516:G:C	F546L	1.000
11:128981516:G:T	F546L	1.000
11:128981517:A:C	F546C	1.000
11:128981517:A:G	F546S	1.000
11:128981518:A:G	F546L	1.000
11:128981518:A:T	F546I	1.000
11:128981520:G:T	A545D	1.000
11:128981550:A:T	I535K	1.000
11:128981561:T:A	R531S	1.000
11:128981561:T:G	R531S	1.000
11:128981829:C:A	R531I	1.000
11:128981829:C:G	R531T	1.000
11:128981832:A:G	L530S	1.000
11:128981835:A:G	L529P	1.000
11:128981835:A:T	L529Q	1.000
11:128981837:G:C	N528K	1.000
11:128981837:G:T	N528K	1.000

dbSNP variants (sampled 300 via entrez): RS1000001520 (11:129097805 A>T), RS1000001892 (11:129004919 A>C,G,T), RS1000020251 (11:129232122 G>T), RS1000029590 (11:129261985 T>C), RS1000034591 (11:129112060 A>C), RS1000057620 (11:129181357 G>T), RS1000057996 (11:129017182 A>G), RS1000068676 (11:129174529 C>T), RS1000079123 (11:129092728 C>T), RS1000091237 (11:129270534 G>A,T), RS1000109683 (11:129017469 GA>G,GAA), RS1000136762 (11:129049049 G>A), RS1000139739 (11:129268177 A>G), RS1000142188 (11:129186442 G>A), RS1000157116 (11:128966231 A>C,T)

Disease associations

OMIM: gene MIM:608541 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): neurodevelopmental disorder (MONDO:0700092), ependymoma (MONDO:0016698)

Orphanet (1): Ependymoma (Orphanet:251636)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001820_13	Metabolite levels (5-HIAA)	5.000000e-07
GCST005094_10	Iris color (L* coordinate)	7.000000e-06
GCST006976_127	Macular thickness	2.000000e-08
GCST007354_10	Intracranial aneurysm	9.000000e-27
GCST010002_202	Refractive error	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005132	5-HIAA measurement
EFO:0003949	eye color

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_SD35	HAP1 ARHGAP32 (-) 1	Cancer cell line	Male
CVCL_SD36	HAP1 ARHGAP32 (-) 2	Cancer cell line	Male
CVCL_XL45	HAP1 ARHGAP32 (-) 3	Cancer cell line	Male
CVCL_XL46	HAP1 ARHGAP32 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

297 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
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
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
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial