ARAP3

Summary

ARAP3 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3, HGNC:24097) is a protein-coding gene on chromosome 5q31.3, encoding Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (Q8WWN8). Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members.

This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined.

Source: NCBI Gene 64411 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lymphedema (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 259 total
• Druggable target: yes
• MANE Select transcript: NM_022481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24097
Approved symbol	ARAP3
Name	ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21065, DRAG1
Ensembl gene	ENSG00000120318
Ensembl biotype	protein_coding
OMIM	606647
Entrez	64411

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000239440, ENST00000504448, ENST00000508305, ENST00000512390, ENST00000513878, ENST00000524066, ENST00000626478, ENST00000890873, ENST00000890874, ENST00000890875, ENST00000890876, ENST00000925545, ENST00000925546, ENST00000955414, ENST00000955415

RefSeq mRNA: 1 — MANE Select: NM_022481 NM_022481

CCDS: CCDS4266

Canonical transcript exons

ENST00000239440 — 33 exons

Exon	Start	End
ENSE00001086050	141672552	141672658
ENSE00001086052	141673013	141673133
ENSE00001086053	141672741	141672925
ENSE00001086054	141673401	141673470
ENSE00001158552	141661684	141661789
ENSE00001158562	141662043	141662255
ENSE00001158589	141666424	141666643
ENSE00001158596	141669709	141669811
ENSE00001158641	141672102	141672301
ENSE00001158683	141673605	141673808
ENSE00001158693	141679545	141679656
ENSE00001158700	141679761	141679822
ENSE00001399306	141682173	141682230
ENSE00001399919	141679963	141680503
ENSE00003239867	141671570	141671752
ENSE00003285270	141671895	141671980
ENSE00003300073	141670512	141670628
ENSE00003418010	141671265	141671400
ENSE00003440829	141669922	141670063
ENSE00003476432	141656064	141656099
ENSE00003493032	141658579	141658653
ENSE00003495384	141659408	141659476
ENSE00003545424	141655362	141655400
ENSE00003593751	141665311	141665374
ENSE00003595986	141655621	141655758
ENSE00003620946	141664922	141665085
ENSE00003637496	141656504	141656637
ENSE00003651057	141656718	141656846
ENSE00003662863	141655869	141655932
ENSE00003670504	141656194	141656276
ENSE00003672599	141659779	141659926
ENSE00003672727	141658365	141658479
ENSE00003847310	141653402	141654435

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 93.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6163 / max 156.7750, expressed in 1427 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63864	7.6202	1405
63863	1.3348	718
63862	0.6421	265
63861	0.0192	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	93.52	gold quality
right lung	UBERON:0002167	92.48	gold quality
blood	UBERON:0000178	90.38	gold quality
upper lobe of left lung	UBERON:0008952	89.70	gold quality
tendon of biceps brachii	UBERON:0008188	89.57	gold quality
upper lobe of lung	UBERON:0008948	89.25	gold quality
heart left ventricle	UBERON:0002084	87.94	gold quality
cardiac ventricle	UBERON:0002082	87.80	gold quality
omental fat pad	UBERON:0010414	87.40	gold quality
peritoneum	UBERON:0002358	87.36	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.16	gold quality
endocervix	UBERON:0000458	86.35	gold quality
right atrium auricular region	UBERON:0006631	86.31	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.10	gold quality
metanephros cortex	UBERON:0010533	85.94	gold quality
ventricular zone	UBERON:0003053	85.91	gold quality
lung	UBERON:0002048	85.68	gold quality
ganglionic eminence	UBERON:0004023	85.68	gold quality
heart	UBERON:0000948	85.42	gold quality
granulocyte	CL:0000094	85.41	gold quality
body of uterus	UBERON:0009853	85.05	gold quality
right lobe of thyroid gland	UBERON:0001119	84.86	gold quality
cardiac atrium	UBERON:0002081	84.51	gold quality
ectocervix	UBERON:0012249	84.47	gold quality
right coronary artery	UBERON:0001625	84.32	gold quality
adipose tissue	UBERON:0001013	84.17	gold quality
left uterine tube	UBERON:0001303	83.96	gold quality
urethra	UBERON:0000057	83.77	gold quality
connective tissue	UBERON:0002384	83.57	gold quality
left lobe of thyroid gland	UBERON:0001120	83.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

32 targeting ARAP3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-12121	99.99	66.64	255
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-3671	99.90	73.04	3897
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-6822-3P	96.60	66.06	680

Literature-anchored findings (GeneRIF, showing 12)

• The catalytic domain of ARF-GAP alone is sufficient to initiate uncoating of liposome-derived COPI-coated vesicles. ARF-GAP activity is not required for COPI coat assembly & does not seem to be an essential coat component of COPI vesicles. (PMID:12832619)
• ARAP3 has a role in integrin-mediated tyrosine kinase signalling pathways controlling Rho GTPases and cell spreading (PMID:15546919)
• ARAP3 deficiency produced by antisense expression of an ARAP3 EST impaired entry of anthrax PA and its bound toxigenic moieties into both human and mouse cells, resulting in reduced toxin sensitivity (PMID:15569923)
• In a yeast two-hybrid screen for new interaction partners of Arap3, the PI 5’-phosphatase SHIP2 was identified as an interaction partner of Arap3. (PMID:17314030)
• None of the individual PH domains can bind to PtdIns(3,4,5)P3; rather, a fragment comprising two PH domains and an N-terminal linker is minimally required for binding. (PMID:19786092)
• ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells. (PMID:21076469)
• The structural basis for the interaction between Arap3 and Vav2, hydrophobic pockets and binding specificity. (PMID:22750419)
• Phosphoinositide 3-OH kinase (PI3K) is input into the regulation of beta2 integrin activity, and processes dependent on its responses, by signaling through its effector ARAP3. (PMID:23180820)
• structural and binding affinity between odin and arap3 (PMID:23239578)
• Structural Basis for the Specific Recognition of RhoA by the Dual GTPase-activating Protein ARAP3. (PMID:27311713)
• Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3. (PMID:36674645)
• ARAP3 protects from excessive formylated peptide-induced microvascular leakage by acting on endothelial cells and neutrophils. (PMID:38734878)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arap3	ENSDARG00000076801
mus_musculus	Arap3	ENSMUSG00000024451
rattus_norvegicus	Arap3	ENSRNOG00000055527

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 — Q8WWN8 (reviewed: Q8WWN8)

Alternative names: Centaurin-delta-3

All UniProt accessions (3): Q8WWN8, G5E9Y3, Q05CH1

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.

Subunit / interactions. Interacts (via SAM domain) with INPPL1/SHIP2.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Cell projection. Lamellipodium. Ruffle.

Post-translational modifications. Tyrosine phosphorylated at a low basal level. PDGF treatment stimulates phosphorylation. Tyrosine phosphorylation is increased in cells that are in the process of becoming attached to a substrate and that start spreading and flattening.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WWN8-1	1	yes
Q8WWN8-2	2

RefSeq proteins (1): NP_071926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR001164	ArfGAP_dom	Domain
IPR001660	SAM	Domain
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR037858	RhoGAP_ARAP	Domain
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR052227	Arf-Rho-GAP_ANK-PH_domain	Family

Pfam: PF00169, PF00620, PF00788, PF01412, PF07647

UniProt features (69 total): helix 23, strand 10, domain 7, turn 6, compositionally biased region 5, modified residue 5, sequence variant 4, region of interest 3, splice variant 2, chain 1, site 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7A9B	X-RAY DIFFRACTION	2
7YIR	X-RAY DIFFRACTION	2.1
5JCP	X-RAY DIFFRACTION	2.1
5JD0	X-RAY DIFFRACTION	2.3
7YIS	X-RAY DIFFRACTION	3.3
2KG5	SOLUTION NMR
2LNW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWN8-F1	68.20	0.23

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

Post-translational modifications (5): 1348, 1403, 1408, 1444, 1480

Mutagenesis-validated functional residues (1):

Position	Phenotype
307–308	loss of ptdins(3,4,5)p3 binding.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 197 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, LFA1_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, TTGGGAG_MIR150, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, PID_PI3KCI_PATHWAY, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, IK2_01, KEGG_ENDOCYTOSIS, IK3_01, BOQUEST_STEM_CELL_DN

GO Biological Process (5): cytoskeleton organization (GO:0007010), signal transduction (GO:0007165), vesicle-mediated transport (GO:0016192), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (6): phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), zinc ion binding (GO:0008270), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), GTPase activator activity (GO:0005096), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): ruffle (GO:0001726), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), lamellipodium (GO:0030027), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	4
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
GTPase activity	2
cell leading edge	2
plasma membrane bounded cell projection	2
organelle organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transport	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
anion binding	1
phosphatidylinositol phosphate binding	1
transition metal ion binding	1
phosphatidylinositol bisphosphate binding	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARAP3	ARF6	P26438	798
ARAP3	SH3KBP1	Q96B97	708
ARAP3	INPPL1	O15357	690
ARAP3	ANK2	Q01484	576
ARAP3	PLEK2	Q9NYT0	566
ARAP3	PLEK	P08567	564
ARAP3	ANK3	Q12955	558
ARAP3	ANK1	P16157	557
ARAP3	RHOA	P06749	474
ARAP3	AGFG2	O95081	441
ARAP3	LRPAP1	P30533	417
ARAP3	RASA1	P20936	396
ARAP3	ZBTB32	Q9Y2Y4	385
ARAP3	APBB1IP	Q7Z5R6	374
ARAP3	PIAS1	O75925	362

IntAct

64 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
SH3KBP1	ARAP3	psi-mi:“MI:0915”(physical association)	0.670
ARAP3	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.670
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
ASB6	POLR2D	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
rep	ARAP3	psi-mi:“MI:0915”(physical association)	0.490
ARAP3	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ARAP3	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
B4GALT2	LENG9	psi-mi:“MI:0914”(association)	0.350
ATG7	IFT56	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
INF2	PIPSL	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HES6	RGPD3	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CLASRP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
D2HGDH	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PLBD1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PSG11	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
CRYBB3	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): ARAP3 (Affinity Capture-MS), ARAP3 (Two-hybrid), ARAP3 (Affinity Capture-MS), ARAP3 (Affinity Capture-MS), INPPL1 (Two-hybrid), SH3KBP1 (Two-hybrid), CD2AP (Two-hybrid), TNKS2 (Two-hybrid), ANKS1A (Two-hybrid), ARHGEF6 (Two-hybrid), GGA3 (Two-hybrid), PARD6B (Two-hybrid), SAMHD1 (Two-hybrid), INPPL1 (Affinity Capture-Western), ARAP3 (Affinity Capture-Western)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARAP3	“down-regulates activity”	RAC1	“gtpase-activating protein”
ARAP3	“down-regulates activity”	CDC42	“gtpase-activating protein”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	206
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4869 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141654432:TTGG:T	acceptor_gain	1.0000
5:141654433:TGG:T	acceptor_gain	1.0000
5:141654433:TGGCT:T	acceptor_loss	1.0000
5:141654434:GG:G	acceptor_gain	1.0000
5:141654435:GC:G	acceptor_loss	1.0000
5:141654436:C:CC	acceptor_gain	1.0000
5:141654437:T:A	acceptor_loss	1.0000
5:141654446:A:AC	acceptor_gain	1.0000
5:141655396:CGCCG:C	acceptor_gain	1.0000
5:141655398:CCG:C	acceptor_gain	1.0000
5:141655399:CG:C	acceptor_gain	1.0000
5:141655399:CGC:C	acceptor_gain	1.0000
5:141655401:C:CC	acceptor_gain	1.0000
5:141655406:C:CT	acceptor_gain	1.0000
5:141655408:CAGG:C	acceptor_gain	1.0000
5:141655409:A:T	acceptor_gain	1.0000
5:141655411:G:C	acceptor_gain	1.0000
5:141655411:G:GC	acceptor_gain	1.0000
5:141655416:G:C	acceptor_gain	1.0000
5:141655416:G:GC	acceptor_gain	1.0000
5:141655423:C:CT	acceptor_gain	1.0000
5:141655424:A:T	acceptor_gain	1.0000
5:141655615:CCTTA:C	donor_loss	1.0000
5:141655616:CTTA:C	donor_loss	1.0000
5:141655617:TTAC:T	donor_loss	1.0000
5:141655618:TACCA:T	donor_loss	1.0000
5:141655619:A:AC	donor_gain	1.0000
5:141655619:ACCA:A	donor_loss	1.0000
5:141655620:C:CT	donor_gain	1.0000
5:141655620:CCA:C	donor_gain	1.0000

AlphaMissense

9955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141659807:A:G	L1080P	1.000
5:141659882:A:C	L1055W	1.000
5:141659882:A:G	L1055S	1.000
5:141659897:A:G	M1050T	1.000
5:141661690:A:G	L1038P	1.000
5:141662057:C:G	W1000S	1.000
5:141662058:A:G	W1000R	1.000
5:141662058:A:T	W1000R	1.000
5:141662113:T:A	K981N	1.000
5:141662113:T:G	K981N	1.000
5:141662117:A:G	L980P	1.000
5:141662186:A:G	F957S	1.000
5:141664944:G:C	C926W	1.000
5:141664946:A:G	C926R	1.000
5:141664963:G:C	P920R	1.000
5:141664963:G:T	P920H	1.000
5:141672299:A:G	F463S	1.000
5:141673030:A:G	F359S	1.000
5:141673063:A:G	F348S	1.000
5:141673458:G:C	F305L	1.000
5:141673458:G:T	F305L	1.000
5:141673460:A:G	F305L	1.000
5:141673619:C:A	K296N	1.000
5:141673619:C:G	K296N	1.000
5:141656799:A:G	W1192R	0.999
5:141656799:A:T	W1192R	0.999
5:141658451:A:G	L1147P	0.999
5:141659433:A:G	L1104P	0.999
5:141659807:A:C	L1080R	0.999
5:141659807:A:T	L1080H	0.999

dbSNP variants (sampled 300 via entrez): RS1000030588 (5:141678362 G>A), RS1000136688 (5:141656907 C>G), RS1000186318 (5:141658421 G>A), RS1000236119 (5:141664256 C>T), RS1000317841 (5:141653364 C>T), RS1000366850 (5:141676881 C>G), RS1000444419 (5:141670640 A>G,T), RS1000562712 (5:141670951 G>A,C), RS1000567161 (5:141662510 T>C), RS1000674385 (5:141675828 C>A), RS1000758915 (5:141660429 G>A,C), RS1000778446 (5:141679371 C>A,T), RS1001194225 (5:141660146 G>A), RS1001228317 (5:141656385 G>A,C), RS1001255031 (5:141681353 A>C)

Disease associations

OMIM: gene MIM:606647 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
lymphedema	Moderate	Autosomal dominant

Mondo (2): prostate cancer (MONDO:0008315), lymphedema (MONDO:0019297)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002636_7	Diffuse large B cell lymphoma	6.000000e-08
GCST003073_13	Cerebral amyloid deposition (PET imaging)	2.000000e-07
GCST003073_3	Cerebral amyloid deposition (PET imaging)	1.000000e-06
GCST004748_47	Lung cancer	3.000000e-06
GCST006231_28	Mean arterial pressure	7.000000e-06
GCST008363_109	Offspring birth weight	2.000000e-08
GCST009391_1922	Metabolite levels	4.000000e-06
GCST009523_36	Household income	4.000000e-08
GCST010397_40	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06
GCST011154_5	Fasting plasma glucose	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0006340	mean arterial pressure
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010464	beta-aminoisobutyric acid measurement
EFO:0009695	household income
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008209	Lymphedema	C15.604.496
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066439 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects methylation, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
muconaldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	decreases methylation	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	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
CHEMBL5611380	Binding	Binding affinity to N-terminal His6 tagged human ARAP3 Sam domain (1 to 80 residues) extracted from Escherichia coli BL21 (DE3) cells at 300 uM by NMR spectroscopy	Inhibition of the EphA2-Sam/Ship2-Sam Association through Peptide Ligands: Studying the Combined Effect of Charge and Aromatic Character. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1JU	Abcam HeLa ARAP3 KO	Cancer cell line	Female
CVCL_SD23	HAP1 ARAP3 (-) 1	Cancer cell line	Male
CVCL_SD24	HAP1 ARAP3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00852930	PHASE4	COMPLETED	Low Level Laser Treatment and Breast Cancer Related Lymphedema
NCT01068431	PHASE4	COMPLETED	Short Term Effectiveness Study of Juxta-Fit Versus Trico Bandages in the Treatment of Leg Lymphedema
NCT02257970	PHASE4	COMPLETED	Lymphedema Study for Arm or Leg Lymphedema
NCT02375945	PHASE4	COMPLETED	Comparison Between a Non-elastic Falcro Device and Current Method After Total Knee Arthroplasty
NCT03584633	PHASE4	COMPLETED	Effect of Exercise on Indocyanine Green (ICG) Lymphography Imaging
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer