ARHGAP40

Summary

ARHGAP40 (Rho GTPase activating protein 40, HGNC:16226) is a protein-coding gene on chromosome 20q11.23, encoding Rho GTPase-activating protein 40 (Q5TG30). GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Predicted to enable GTPase activator activity. Predicted to be involved in regulation of actin filament polymerization and regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 343578 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 121 total
• MANE Select transcript: NM_001164431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16226
Approved symbol	ARHGAP40
Name	Rho GTPase activating protein 40
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	dJ1100H13.4
Ensembl gene	ENSG00000124143
Ensembl biotype	protein_coding
Entrez	343578

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000243967, ENST00000373345, ENST00000414158, ENST00000906550

RefSeq mRNA: 1 — MANE Select: NM_001164431 NM_001164431

Canonical transcript exons

ENST00000373345 — 15 exons

Exon	Start	End
ENSE00000844666	38637708	38637799
ENSE00000844667	38638761	38638838
ENSE00000844668	38639227	38639386
ENSE00000844669	38641726	38641808
ENSE00000844670	38643704	38643910
ENSE00000906859	38634620	38634785
ENSE00001460332	38648643	38648698
ENSE00001460333	38646957	38647126
ENSE00001460334	38646047	38646187
ENSE00001595205	38649757	38650653
ENSE00001618106	38629502	38629650
ENSE00001680030	38626995	38627215
ENSE00001710876	38628927	38629002
ENSE00001798979	38623359	38623558
ENSE00002246937	38601809	38602079

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 96.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4839 / max 80.3494, expressed in 159 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184579	0.2251	97
184578	0.1300	56
184577	0.1288	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.78	gold quality
skin of leg	UBERON:0001511	89.25	gold quality
zone of skin	UBERON:0000014	88.87	gold quality
skin of abdomen	UBERON:0001416	88.32	gold quality
esophagus mucosa	UBERON:0002469	87.42	gold quality
metanephros cortex	UBERON:0010533	77.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.42	gold quality
vagina	UBERON:0000996	67.09	gold quality
thoracic mammary gland	UBERON:0005200	67.03	gold quality
prostate gland	UBERON:0002367	65.17	gold quality
esophagus	UBERON:0001043	63.60	gold quality
urinary bladder	UBERON:0001255	63.02	gold quality
cortex of kidney	UBERON:0001225	62.40	gold quality
minor salivary gland	UBERON:0001830	62.30	gold quality
adult mammalian kidney	UBERON:0000082	61.84	gold quality
body of stomach	UBERON:0001161	61.52	gold quality
saliva-secreting gland	UBERON:0001044	60.88	gold quality
duodenum	UBERON:0002114	60.06	gold quality
left testis	UBERON:0004533	59.57	gold quality
fundus of stomach	UBERON:0001160	59.37	gold quality
stomach	UBERON:0000945	59.26	gold quality
right testis	UBERON:0004534	59.13	gold quality
testis	UBERON:0000473	59.07	gold quality
kidney	UBERON:0002113	58.66	gold quality
caudate nucleus	UBERON:0001873	56.81	gold quality
right lung	UBERON:0002167	56.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	55.24	gold quality
tonsil	UBERON:0002372	53.99	gold quality
putamen	UBERON:0001874	53.60	gold quality
right lobe of thyroid gland	UBERON:0001119	52.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting ARHGAP40, 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-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-5589-5P	98.34	64.82	1148

Literature-anchored findings (GeneRIF, showing 1)

• Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation. (PMID:37822129)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arhgap40	ENSMUSG00000074625
rattus_norvegicus	Arhgap40	ENSRNOG00000015359
drosophila_melanogaster	conu	FBGN0039994

Paralogs (3): ARHGAP28 (ENSG00000088756), ARHGAP18 (ENSG00000146376), ARHGAP19 (ENSG00000213390)

Protein

Protein identifiers

Rho GTPase-activating protein 40 — Q5TG30 (reviewed: Q5TG30)

Alternative names: Rho-type GTPase-activating protein 40

All UniProt accessions (3): Q5TG30, H0Y7S1, H7BXE0

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

RefSeq proteins (1): NP_001157903* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR057323	RHG40/28/18_ubiquitin	Domain

Pfam: PF00620, PF25442

UniProt features (9 total): sequence variant 3, region of interest 2, chain 1, domain 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TG30-F1	72.96	0.45

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

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle

MSigDB gene sets: 50 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, chr20q11, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_LENGTH, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_ACTIN_POLYMERIZATION_OR_DEPOLYMERIZATION

GO Biological Process (3): signal transduction (GO:0007165), regulation of actin filament polymerization (GO:0030833), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

553 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP40	C11orf98	E9PRG8	507
ARHGAP40	SLC32A1	Q9H598	477
ARHGAP40	VSTM2L	Q96N03	468
ARHGAP40	KIAA1755	Q5JYT7	442
ARHGAP40	KRTDAP	P60985	384
ARHGAP40	ZNF428	Q96B54	375
ARHGAP40	C5orf34	Q96MH7	371
ARHGAP40	DLGAP4	Q9Y2H0	366
ARHGAP40	RFPL4A	A6NLU0	348
ARHGAP40	ZNF677	Q86XU0	348
ARHGAP40	VGLL1	Q99990	343
ARHGAP40	DHX35	Q9H5Z1	328
ARHGAP40	UPK1A	O00322	327
ARHGAP40	TARM1	B6A8C7	321
ARHGAP40	SRC	P12931	304

IntAct

3 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350
HS3ST3B1	HSPA9	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A140LI67, A6QQV9, A7UA95, B1AVH7, B5DFA1, B5KFD7, D2H0G5, E7F221, E9Q6X9, F1LYQ8, F8VPU2, O09039, O88900, O94887, O95382, P0CE43, P97680, Q03160, Q13322, Q14449, Q14451, Q14B46, Q1RMW5, Q3U5C8, Q4LDD4, Q5ICW4, Q5JV73, Q5RAB8, Q5TG30, Q60760, Q68DX3, Q6P112, Q80TI1, Q8C6B2, Q8R0L1, Q8R5G7, Q8WWN8, Q91VS8, Q921Q7, Q969H4

Diamond homologs: A1A4S6, A6NI28, A6X8Z5, A7E300, B2RQE8, B5DFQ4, B9VTT2, D3ZFJ3, D3ZZN9, E9Q6X9, F1LQX4, O43182, O60890, P0CAX5, P15882, P30337, P55194, P81128, P83509, P98171, Q07960, Q08DP6, Q13459, Q14CB8, Q17QN0, Q17R89, Q2M1Z3, Q3KRB8, Q54FF4, Q54PG5, Q54TH9, Q54VW7, Q553X3, Q559A0, Q5FWK3, Q5SSM3, Q5TG30, Q5U4T3, Q62172, Q63358

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARHGAP40	“down-regulates activity”	RHOA	“gtpase-activating protein”
ARHGAP40	“down-regulates activity”	CDC42	“gtpase-activating protein”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2900 predictions. Top by Δscore:

Variant	Effect	Δscore
20:38623555:GAGG:G	donor_gain	1.0000
20:38623557:GG:G	donor_gain	1.0000
20:38623558:GG:G	donor_gain	1.0000
20:38627189:G:T	donor_gain	1.0000
20:38627213:GGG:G	donor_gain	1.0000
20:38627214:GG:G	donor_gain	1.0000
20:38627214:GGG:G	donor_gain	1.0000
20:38627215:GG:G	donor_gain	1.0000
20:38628924:T:G	acceptor_gain	1.0000
20:38629492:C:A	acceptor_gain	1.0000
20:38634615:A:AG	acceptor_gain	1.0000
20:38634618:A:AG	acceptor_gain	1.0000
20:38634619:G:GG	acceptor_gain	1.0000
20:38634619:GAA:G	acceptor_gain	1.0000
20:38637706:A:AG	acceptor_gain	1.0000
20:38637707:G:GG	acceptor_gain	1.0000
20:38637707:GAA:G	acceptor_gain	1.0000
20:38637797:GCC:G	donor_gain	1.0000
20:38637800:G:GG	donor_gain	1.0000
20:38638755:T:A	acceptor_gain	1.0000
20:38638756:GACA:G	acceptor_loss	1.0000
20:38638758:CA:C	acceptor_loss	1.0000
20:38638759:A:AG	acceptor_gain	1.0000
20:38638760:G:GA	acceptor_gain	1.0000
20:38638760:GC:G	acceptor_gain	1.0000
20:38638760:GCT:G	acceptor_gain	1.0000
20:38638834:TCA:T	donor_gain	1.0000
20:38639382:GCCTA:G	donor_gain	1.0000
20:38639387:G:GG	donor_gain	1.0000
20:38646184:GGCG:G	donor_gain	1.0000

AlphaMissense

4058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:38649822:T:A	W615R	0.986
20:38649822:T:C	W615R	0.986
20:38646075:G:C	R480P	0.976
20:38646056:T:C	F474L	0.975
20:38646058:C:A	F474L	0.975
20:38646058:C:G	F474L	0.975
20:38634714:A:T	E240V	0.974
20:38639316:A:C	K350N	0.974
20:38639316:A:T	K350N	0.974
20:38639371:T:C	F369L	0.973
20:38639373:C:A	F369L	0.973
20:38639373:C:G	F369L	0.973
20:38639315:A:T	K350I	0.971
20:38634717:T:C	L241P	0.970
20:38627015:T:A	W67R	0.967
20:38627015:T:C	W67R	0.967
20:38627017:G:C	W67C	0.967
20:38627017:G:T	W67C	0.967
20:38643756:T:C	M419T	0.965
20:38634669:T:C	L225S	0.963
20:38649824:G:C	W615C	0.963
20:38649824:G:T	W615C	0.963
20:38643905:T:A	W469R	0.962
20:38643905:T:C	W469R	0.962
20:38643757:G:A	M419I	0.959
20:38643757:G:C	M419I	0.959
20:38643757:G:T	M419I	0.959
20:38627107:G:C	Q97H	0.957
20:38627107:G:T	Q97H	0.957
20:38634680:G:C	D229H	0.955

dbSNP variants (sampled 300 via entrez): RS1000017413 (20:38611605 T>A,C), RS1000044455 (20:38617501 C>T), RS1000059092 (20:38619243 TC>T), RS1000091014 (20:38600206 C>T), RS1000153454 (20:38610671 A>G), RS1000174143 (20:38622986 T>C), RS1000206651 (20:38622687 C>G), RS1000349004 (20:38648719 C>A), RS1000349825 (20:38631536 T>C), RS1000432662 (20:38628793 A>G), RS1000695988 (20:38650021 G>T), RS1000726657 (20:38649828 C>T), RS1000736185 (20:38627894 C>T), RS1000800321 (20:38649528 C>T), RS1000808693 (20:38629016 A>C,G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003659_4	Modified Stumvoll Insulin Sensitivity Index (BMI interaction)	4.000000e-09
GCST007831_8	Anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004471	insulin sensitivity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
abrine	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Phthalic Acids	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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