ARHGAP39

Summary

ARHGAP39 (Rho GTPase activating protein 39, HGNC:29351) is a protein-coding gene on chromosome 8q24.3, encoding Rho GTPase-activating protein 39 (Q9C0H5).

Predicted to enable GTPase activator activity. Involved in postsynapse organization. Is active in glutamatergic synapse.

Source: NCBI Gene 80728 — RefSeq curated summary.

At a glance

• Gene–disease (curated): central nervous system malformation (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 230 total — 1 pathogenic
• MANE Select transcript: NM_025251

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29351
Approved symbol	ARHGAP39
Name	Rho GTPase activating protein 39
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1688, Vilse, CrGAP
Ensembl gene	ENSG00000147799
Ensembl biotype	protein_coding
OMIM	615880
Entrez	80728

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000276826, ENST00000377307, ENST00000528810, ENST00000905349, ENST00000905350, ENST00000905351, ENST00000905352, ENST00000934378, ENST00000934379, ENST00000948833

RefSeq mRNA: 3 — MANE Select: NM_025251 NM_001308207, NM_001308208, NM_025251

CCDS: CCDS34971, CCDS78374

Canonical transcript exons

ENST00000377307 — 12 exons

Exon	Start	End
ENSE00000981813	144547127	144548489
ENSE00001055692	144533126	144533325
ENSE00001055693	144555560	144555643
ENSE00001055697	144532305	144532396
ENSE00001055699	144534129	144534202
ENSE00001115698	144530702	144530871
ENSE00001132486	144580846	144581277
ENSE00001212011	144545249	144545810
ENSE00001212102	144529179	144530616
ENSE00001324258	144605535	144605695
ENSE00001473494	144537721	144537813
ENSE00003937730	144685686	144685846

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 93.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8469 / max 44.5483, expressed in 1225 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95703	2.4720	1016
95704	0.7957	485
95702	0.5792	288

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	93.66	gold quality
oviduct epithelium	UBERON:0004804	93.30	gold quality
right uterine tube	UBERON:0001302	92.41	gold quality
tibial nerve	UBERON:0001323	89.02	gold quality
oocyte	CL:0000023	85.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.79	gold quality
left testis	UBERON:0004533	84.56	gold quality
right testis	UBERON:0004534	84.42	gold quality
spinal cord	UBERON:0002240	83.94	gold quality
right frontal lobe	UBERON:0002810	83.43	gold quality
testis	UBERON:0000473	83.19	gold quality
cortical plate	UBERON:0005343	82.96	gold quality
secondary oocyte	CL:0000655	82.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.91	gold quality
bronchial epithelial cell	CL:0002328	81.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.63	silver quality
cerebellar hemisphere	UBERON:0002245	81.25	gold quality
bronchus	UBERON:0002185	81.24	gold quality
cerebellar cortex	UBERON:0002129	81.17	gold quality
postcentral gyrus	UBERON:0002581	81.12	gold quality
anterior cingulate cortex	UBERON:0009835	80.54	gold quality
cerebellum	UBERON:0002037	80.34	gold quality
frontal cortex	UBERON:0001870	80.17	gold quality
neocortex	UBERON:0001950	80.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.02	gold quality
fallopian tube	UBERON:0003889	79.96	gold quality
parietal lobe	UBERON:0001872	79.90	gold quality
superior frontal gyrus	UBERON:0002661	79.61	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.76
E-CURD-10	no	20.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting ARHGAP39, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-4505	99.27	67.81	2678

Literature-anchored findings (GeneRIF, showing 3)

• Biological function analysis of ARHGAP39 as an independent prognostic biomarker in hepatocellular carcinoma. (PMID:37059586)
• ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer. (PMID:37189064)
• A homozygous variant in ARHGAP39 is associated with lethal cerebellar vermis hypoplasia in a consanguineous Saudi family. (PMID:39455833)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap39	ENSDARG00000100007
mus_musculus	Arhgap39	ENSMUSG00000033697
rattus_norvegicus	Arhgap39	ENSRNOG00000016566
drosophila_melanogaster	RhoGAP93B	FBGN0038853
caenorhabditis_elegans	Y92H12BM.1	WBGENE00022367
caenorhabditis_elegans	Y92H12BL.7	WBGENE00305050

Protein

Protein identifiers

Rho GTPase-activating protein 39 — Q9C0H5 (reviewed: Q9C0H5)

All UniProt accessions (1): Q9C0H5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0H5-1	1	yes
Q9C0H5-2	2

RefSeq proteins (3): NP_001295136, NP_001295137, NP_079527* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR000857	MyTH4_dom	Domain
IPR001202	WW_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR038185	MyTH4_dom_sf	Homologous_superfamily

Pfam: PF00620, PF00784

UniProt features (28 total): modified residue 11, compositionally biased region 5, domain 4, region of interest 4, initiator methionine 1, chain 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0H5-F1	59.42	0.26

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

Post-translational modifications (11): 2, 169, 286, 384, 388, 406, 407, 604, 690, 715, 726

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-428543	Inactivation of CDC42 and RAC1
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-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle

MSigDB gene sets: 136 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, PATIL_LIVER_CANCER, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, CUI_TCF21_TARGETS_2_UP, GOCC_SYNAPSE, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_SYNAPSE_ORGANIZATION

GO Biological Process (3): signal transduction (GO:0007165), regulation of small GTPase mediated signal transduction (GO:0051056), postsynapse organization (GO:0099173)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	10
Signaling by ROBO receptors	1

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
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cellular component organization	1
synapse organization	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
synapse	1

Protein interactions and networks

STRING

1300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP39	MROH1	Q8NDA8	697
ARHGAP39	TMEM276	P0DTL5	690
ARHGAP39	CNKSR2	Q8WXI2	678
ARHGAP39	SACK1H	Q6ZRV2	654
ARHGAP39	CPSF1	Q10570	633
ARHGAP39	ROBO4	Q8WZ75	577
ARHGAP39	ARHGEF7	Q14155	538
ARHGAP39	PAK4	O96013	498
ARHGAP39	MAPK15	Q8TD08	482
ARHGAP39	TMEM35A	Q53FP2	474
ARHGAP39	ARHGEF6	Q15052	468
ARHGAP39	PPP1R16A	Q96I34	461
ARHGAP39	GRINA	Q7Z429	460
ARHGAP39	ZNF623	O75123	447
ARHGAP39	LRRC14	Q15048	441

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
SPIN2B	WDHD1	psi-mi:“MI:0914”(association)	0.530
CNKSR3	COLGALT2	psi-mi:“MI:0914”(association)	0.530
ARHGAP39	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CTDSPL	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EPHA3	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
EPHA5	C1orf226	psi-mi:“MI:2364”(proximity)	0.270
EPHA7	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EPHA4	ARHGAP39	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (130): ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Affinity Capture-MS), ARHGAP39 (Proximity Label-MS), ARHGAP39 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, A1A5B6, A4D2P6, D7PF45, F1LXF1, O15357, O60346, O75808, P11274, P49796, P52734, P53349, P59672, P70268, P78524, P98174, Q0QWG9, Q13233, Q13905, Q16825, Q3MII6, Q50H33, Q5RDA9, Q62925, Q63433, Q6NS60, Q6P549, Q6PDJ6, Q6WVG3, Q7Z5H3, Q8BL80, Q8BUP8, Q8N2R8, Q8TF61, Q8VHK2, Q8WXD9, Q924W7, Q92625, Q96CX2

Diamond homologs: A2RUV4, A8WRJ2, B0S6J3, B1V8A0, B3DLB3, D4A208, F1LM93, F1LQX4, O43182, O43295, O54834, O60504, O60890, O75044, O94466, O94875, P07751, P07947, P09324, P0CAX5, P0DJJ0, P0DMP2, P10936, P13115, P13395, P15882, P16086, P16546, P27447, P30337, P32793, P46941, P52757, P62993, P62994, P83509, P87379, P97393, P98171, Q02977

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARHGAP39	“down-regulates activity”	RAC1	“gtpase-activating protein”
ARHGAP39	“down-regulates activity”	CDC42	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
EPH-Ephrin signaling	5	48.7×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	68.8×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	188
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425051	NC_000008.10:g.(?145741748)(145958266_?)del	Pathogenic

SpliceAI

2697 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144530616:CCTGG:C	acceptor_loss	1.0000
8:144530697:AGTAC:A	donor_loss	1.0000
8:144530698:GTAC:G	donor_loss	1.0000
8:144530699:TAC:T	donor_loss	1.0000
8:144530701:C:CT	donor_loss	1.0000
8:144530868:GACG:G	acceptor_gain	1.0000
8:144530869:ACG:A	acceptor_gain	1.0000
8:144530869:ACGC:A	acceptor_loss	1.0000
8:144530870:CG:C	acceptor_gain	1.0000
8:144530870:CGC:C	acceptor_gain	1.0000
8:144530871:GC:G	acceptor_loss	1.0000
8:144530872:C:CC	acceptor_gain	1.0000
8:144530873:T:A	acceptor_loss	1.0000
8:144532300:CTCA:C	donor_loss	1.0000
8:144532302:CACCA:C	donor_loss	1.0000
8:144532303:A:AC	donor_gain	1.0000
8:144532304:C:CC	donor_gain	1.0000
8:144532395:CC:C	acceptor_gain	1.0000
8:144532396:CC:C	acceptor_gain	1.0000
8:144532397:C:CC	acceptor_gain	1.0000
8:144532397:CTGC:C	acceptor_loss	1.0000
8:144533122:GCAC:G	donor_loss	1.0000
8:144533123:CACC:C	donor_loss	1.0000
8:144533124:ACCTG:A	donor_loss	1.0000
8:144533125:C:CC	donor_loss	1.0000
8:144533168:T:TA	donor_gain	1.0000
8:144533240:T:TA	donor_gain	1.0000
8:144533321:AGCCC:A	acceptor_gain	1.0000
8:144533322:GCCC:G	acceptor_gain	1.0000
8:144533323:CCC:C	acceptor_gain	1.0000

AlphaMissense

7279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144530465:A:G	L1070P	1.000
8:144530465:A:T	L1070H	1.000
8:144530477:A:G	F1066S	1.000
8:144530546:G:T	P1043H	1.000
8:144530564:A:G	L1037P	1.000
8:144530579:A:C	M1032R	1.000
8:144530847:C:G	R971P	1.000
8:144530854:A:G	W969R	1.000
8:144530854:A:T	W969R	1.000
8:144530856:A:G	L968P	1.000
8:144530858:C:A	K967N	1.000
8:144530858:C:G	K967N	1.000
8:144530862:A:G	L966P	1.000
8:144530865:A:G	L965P	1.000
8:144532344:A:G	W950R	1.000
8:144532344:A:T	W950R	1.000
8:144532360:C:A	K944N	1.000
8:144532360:C:G	K944N	1.000
8:144532364:A:G	L943P	1.000
8:144533126:C:A	R932M	1.000
8:144533128:G:C	F931L	1.000
8:144533128:G:T	F931L	1.000
8:144533129:A:G	F931S	1.000
8:144533130:A:G	F931L	1.000
8:144533177:A:G	L915P	1.000
8:144534160:A:G	L855P	1.000
8:144534171:A:C	C851W	1.000
8:144534181:G:T	A848D	1.000
8:144545276:G:C	H832D	1.000
8:144545296:A:G	L825P	1.000

dbSNP variants (sampled 300 via entrez): RS1000003337 (8:144531076 G>A,C), RS1000006336 (8:144551090 A>G), RS1000015872 (8:144567593 C>T), RS1000019963 (8:144603913 G>A), RS1000027693 (8:144667716 G>T), RS1000029231 (8:144637567 G>A), RS1000031418 (8:144607860 T>A,C), RS1000039648 (8:144691974 A>G), RS1000054779 (8:144532662 G>A), RS1000055759 (8:144609694 G>A,C), RS1000133639 (8:144567865 G>A), RS1000134798 (8:144604139 G>A,T), RS1000143032 (8:144571984 C>G,T), RS1000170563 (8:144682086 G>C), RS1000178055 (8:144671566 C>G,T)

Disease associations

OMIM: gene MIM:615880 | disease phenotypes: MIM:218600

GenCC curated gene-disease

Disease	Classification	Inheritance
central nervous system malformation	Limited	Autosomal recessive

Mondo (2): Baller-Gerold syndrome (MONDO:0009039), central nervous system malformation (MONDO:0020022)

Orphanet (1): Baller-Gerold syndrome (Orphanet:1225)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002598_30	Educational attainment	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009421	Nervous System Malformations	C10.500; C16.131.666
C536788	Craniosynostosis radial aplasia syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	decreases methylation	1
muconaldehyde	decreases expression	1
abrine	increases expression	1
bisphenol S	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases methylation, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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