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ARAP1

gene
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Summary

ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1, HGNC:16925) is a protein-coding gene on chromosome 11q13.4, encoding Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (Q96P48). Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members.

The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 116985 — RefSeq curated summary.

At a glance

  • GWAS associations: 43
  • Clinical variants (ClinVar): 309 total
  • Phenotypes (HPO): 1
  • MANE Select transcript: NM_001040118

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:16925
Approved symbolARAP1
NameArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1
Location11q13.4
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000186635
Ensembl biotypeprotein_coding
OMIM606646
Entrez116985

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 20 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000334211, ENST00000359373, ENST00000393605, ENST00000393609, ENST00000426523, ENST00000427971, ENST00000429686, ENST00000452383, ENST00000465814, ENST00000495878, ENST00000536885, ENST00000536993, ENST00000541623, ENST00000542264, ENST00000542596, ENST00000542612, ENST00000543868, ENST00000544721, ENST00000544958, ENST00000546293, ENST00000852595, ENST00000852596, ENST00000852597, ENST00000852598, ENST00000932329, ENST00000932330, ENST00000932331, ENST00000932332, ENST00000932333, ENST00000952695

RefSeq mRNA: 4 — MANE Select: NM_001040118 NM_001040118, NM_001135190, NM_001369489, NM_015242

CCDS: CCDS41687, CCDS44671, CCDS8217, CCDS91531

Canonical transcript exons

ENST00000393609 — 35 exons

ExonStartEnd
ENSE000014235407271243872712568
ENSE000014705117273251572732597
ENSE000018585647275232872752408
ENSE000022401377272662072727172
ENSE000034674837271102172711141
ENSE000034771877269732372697486
ENSE000034826947269698372697195
ENSE000034857477269332572693470
ENSE000034884767269571872695865
ENSE000034907957269759872697649
ENSE000035030677269498072695097
ENSE000035094227271415272714321
ENSE000035259177270290572703079
ENSE000035262147269275372692785
ENSE000035281157268845572688537
ENSE000035314147269900572699107
ENSE000035351107269791172698106
ENSE000035406317271317672713243
ENSE000035419147271038572710587
ENSE000035455047270164972701783
ENSE000035596257269654972696654
ENSE000035617937270987072709976
ENSE000035740527270580572705890
ENSE000035892017271219672712339
ENSE000036261507269941772699552
ENSE000036371667271143072711499
ENSE000036391317269538772695455
ENSE000036411387268604272686191
ENSE000036469197269369272693805
ENSE000036545217269554272695628
ENSE000036558547270717572707374
ENSE000036601277268743972687502
ENSE000036635137268768872687738
ENSE000036767357268506972685681
ENSE000036825937270415272704334

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.9555 / max 379.3332, expressed in 1818 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter IDTPM avgSamples expressed
12120016.65891779
12119015.36661724
1211898.31021442
1211882.2083676
1212150.6444309
1211830.3286162
1211910.250399
1211860.234172
1211870.208675
1211820.198495

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009498.81gold quality
monocyteCL:000057698.30gold quality
mononuclear cellCL:000084298.09gold quality
right uterine tubeUBERON:000130298.08gold quality
leukocyteCL:000073898.07gold quality
upper lobe of left lungUBERON:000895297.72gold quality
right lungUBERON:000216797.58gold quality
spleenUBERON:000210697.53gold quality
right adrenal gland cortexUBERON:003582797.36gold quality
right adrenal glandUBERON:000123397.24gold quality
left adrenal gland cortexUBERON:003582597.12gold quality
adenohypophysisUBERON:000219697.07gold quality
right lobe of thyroid glandUBERON:000111996.93gold quality
left adrenal glandUBERON:000123496.88gold quality
left lobe of thyroid glandUBERON:000112096.72gold quality
upper lobe of lungUBERON:000894896.71gold quality
gall bladderUBERON:000211096.66gold quality
adrenal cortexUBERON:000123596.60gold quality
right ovaryUBERON:000211896.42gold quality
sural nerveUBERON:001548896.22gold quality
left ovaryUBERON:000211996.15gold quality
apex of heartUBERON:000209896.12gold quality
metanephros cortexUBERON:001053396.10gold quality
endocervixUBERON:000045896.09gold quality
adrenal glandUBERON:000236996.00gold quality
pituitary glandUBERON:000000795.95gold quality
body of uterusUBERON:000985395.83gold quality
stromal cell of endometriumCL:000225595.71gold quality
thyroid glandUBERON:000204695.64gold quality
left uterine tubeUBERON:000130395.61gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes14.18
E-MTAB-8498yes10.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, PAX4, PAX6, PITX2

miRNA regulators (miRDB)

35 targeting ARAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-656-3P100.0072.152788
HSA-MIR-4425100.0067.591049
HSA-MIR-4533100.0069.482758
HSA-MIR-453499.9966.581907
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-MIR-4650-5P99.9864.69999
HSA-MIR-6793-5P99.9765.95758
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-211099.9666.681930
HSA-MIR-427199.8868.322244
HSA-MIR-320299.6667.702737
HSA-MIR-378A-5P99.6566.331311
HSA-MIR-516B-5P99.5666.331495
HSA-MIR-7106-5P99.5367.473574
HSA-MIR-608399.4768.732393
HSA-MIR-428499.3665.251293
HSA-MIR-568399.3668.592083
HSA-MIR-1211399.3267.541072
HSA-MIR-447899.0765.162320
HSA-MIR-60898.9367.832013
HSA-MIR-453998.7867.18888
HSA-MIR-6894-5P98.7063.78809
HSA-MIR-446398.5666.051071
HSA-MIR-4664-5P98.1765.071020
HSA-MIR-6765-3P97.8364.591165
HSA-MIR-393697.6464.47732
HSA-MIR-428797.5567.241247

Literature-anchored findings (GeneRIF, showing 21)

  • ARAP1 acts primarily on Arf6 in vivo. (PMID:18003747)
  • ARAP1 knockdown significantly compromises the localization of death receptor 4 at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. (PMID:18165900)
  • ARAP1 controls the late steps of the endocytic trafficking of the EGF-R (PMID:18764928)
  • ARAP1 regulates the endocytic traffic of EGFR and, consequently, the rate of EGFR signal attenuation (PMID:18939958)
  • Data suggest that ARAP1 is recruited to membranes independently of PtdIns(3,4,5)P(3), the subsequent production of which triggers enzymatic activity. (PMID:19666464)
  • PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells. (PMID:20554524)
  • Of the lead variants from 12 novel type 2 diabetes associated loci, CENTD2 significantly associated with increased plasma glucose values and decreased glucose-stimulated insulin release. (PMID:21267535)
  • ARAP1 associated with CIN85 affects epidermal growth factor receptor endocytic trafficking (PMID:21275903)
  • Arap1 is highly expressed in the renal vasculature, and its expression is suppressed by angiotensin II. (PMID:22357923)
  • a novel molecular mechanism of circular dorsal ruffles ring size control through the ARAP1-Arf1/5 pathway. (PMID:22573888)
  • The proinsulin-decreasing and T2D-risk Alleles are associated with increased ARAP1 mRNA levels in primary human pancreatic islets. (PMID:24439111)
  • Genetic variant rs1552224 of CENTD2 on chromosome 11 contributes to an independent effect as well as joint cumulative effect with rs2237897 of KCNQ1 on the risk of type 2 diabetes mellitus in Chinese Han population. (PMID:25749274)
  • Quantitative trait loci genes analysis reveals association between T2D risk variants at the ARAP1/STARD10 locus and STARD10 but not ARAP1 expression. (PMID:28132686)
  • Low expression of ARAP1 is an independent prognostic biomarker of shorter recurrence free survival in older patients with high grade ovarian serous carcinoma receiving first-line platinum-based antineoplastic therapy. (PMID:31478407)
  • The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells. (PMID:31975379)
  • Increased long non-coding RNA ARAP1-AS1 expression and its prognostic significance in human gastric cancer: a preliminary study. (PMID:32141550)
  • Identifying the association between single nucleotide polymorphisms in KCNQ1, ARAP1, and KCNJ11 and type 2 diabetes mellitus in a Chinese population. (PMID:32922204)
  • LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1. (PMID:32969198)
  • Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans. (PMID:35163144)
  • Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death. (PMID:35758026)
  • Arf GTPase-Activating proteins ADAP1 and ARAP1 regulate incorporation of CD63 in multivesicular bodies. (PMID:38682696)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusArap1ENSMUSG00000032812
rattus_norvegicusArap1ENSRNOG00000019555

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), 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), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 — Q96P48 (reviewed: Q96P48)

Alternative names: Centaurin-delta-2

All UniProt accessions (6): E7EU13, Q96P48, F5GWN4, F5GWQ2, F8WBT0, H0YGD1

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. Activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding and, to a lesser extent, by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) binding. Has a preference for ARF1 and ARF5. Positively regulates the ring size of circular dorsal ruffles and promotes macropinocytosis. Acts as a bridging factor in osteoclasts to control actin and membrane dynamics. Regulates the condensing of osteoclast podosomes into sealing zones which segregate the bone-facing membrane from other membrane domains and are required for osteoclast resorption activity. Also regulates recruitment of the AP-3 complex to endosomal membranes and trafficking of lysosomal membrane proteins to the ruffled membrane border of osteoclasts to modulate bone resorption. Regulates the endocytic trafficking of EGFR. Regulates the incorporation of CD63 and CD9 into multivesicular bodies. Required in the retinal pigment epithelium (RPE) for photoreceptor survival due to its role in promoting RPE phagocytosis.

Subunit / interactions. Interacts with SH3KBP1/CIN85 (via SH3 domains). The interaction is independent of EGF and does not affect ARAP1 GTPase-activating activity but is involved in regulating ubiquitination and endocytic trafficking of EGFR. ARAP1 competes with E3 ubiquitin-protein ligase CBL for binding to SH3KBP1, preventing interaction of CBL with SH3KBP1; this is likely to regulate SH3KBP1-mediated internalization of EGFR. Interacts with TNFRSF10A.

Subcellular location. Cytoplasm. Golgi apparatus. trans-Golgi network. Golgi stack. Cell membrane. Endosome. Multivesicular body. Cell projection. Ruffle. Podosome. Early endosome.

Tissue specificity. Detected in heart, skeletal muscle, spleen, kidney, liver, placenta, lung, peripheral blood leukocytes, adrenal gland, bone marrow, brain, lymph node, mammary gland, prostate, spinal cord, stomach, thyroid and trachea.

Post-translational modifications. Phosphorylated by PTK6 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation; the interaction is mediated by the SH2 domain of PTK6. Phosphorylation promotes association with the Golgi apparatus and endosomes.

Domain organisation. The first PH domain, PH 1, interacts with PtdIns(3,4,5)P3 which stimulates ARAP1 GTPase-activating activity and is also required for ARAP1-mediated regulation of endocytic trafficking of EGFR. It does not mediate PtdIns(3,4,5)P3-dependent recruitment of ARAP1 to membranes although this may be mediated by other PH domains.

Isoforms (7)

UniProt IDNamesCanonical?
Q96P48-66, ARAP1byes
Q96P48-11
Q96P48-22
Q96P48-33
Q96P48-44
Q96P48-55
Q96P48-77

RefSeq proteins (4): NP_001035207, NP_001128662, NP_001356418, NP_056057 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000159RA_domDomain
IPR000198RhoGAP_domDomain
IPR001164ArfGAP_domDomain
IPR001660SAMDomain
IPR001849PH_domainDomain
IPR008936Rho_GTPase_activation_protHomologous_superfamily
IPR011993PH-like_dom_sfHomologous_superfamily
IPR013761SAM/pointed_sfHomologous_superfamily
IPR037278ARFGAP/RecOHomologous_superfamily
IPR037858RhoGAP_ARAPDomain
IPR038508ArfGAP_dom_sfHomologous_superfamily
IPR052227Arf-Rho-GAP_ANK-PH_domainFamily

Pfam: PF00169, PF00536, PF00620, PF00788, PF01412

UniProt features (46 total): modified residue 9, domain 8, mutagenesis site 8, splice variant 7, compositionally biased region 5, region of interest 3, sequence variant 2, chain 1, site 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
4X1VX-RAY DIFFRACTION1.58

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96P48-F175.810.41

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

Post-translational modifications (9): 229, 231, 354, 428, 431, 504, 738, 1428, 1435

Mutagenesis-validated functional residues (8):

PositionPhenotype
23no effect on phosphorylation by ptk6.
81–86reduced interaction with sh3kbp1.
81slightly reduced interaction with sh3kbp1.
86–90reduced interaction with sh3kbp1.
231abolishes phosphorylation by ptk6.
288no effect on phosphorylation by ptk6.
578abolishes effect on circular dorsal ruffle size.
993no effect on regulation of circular dorsal ruffle size.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

IDPathway
R-HSA-8849469PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
R-HSA-8980692RHOA GTPase cycle
R-HSA-9013148CDC42 GTPase cycle
R-HSA-9013149RAC1 GTPase cycle
R-HSA-162582Signal Transduction
R-HSA-194315Signaling by Rho GTPases
R-HSA-8848021Signaling by PTK6
R-HSA-9006927Signaling by Non-Receptor Tyrosine Kinases
R-HSA-9012999RHO GTPase cycle
R-HSA-9716542Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 278 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, WANG_CLIM2_TARGETS_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE

GO Biological Process (16): positive regulation of receptor recycling (GO:0001921), regulation of receptor internalization (GO:0002090), actin filament organization (GO:0007015), signal transduction (GO:0007165), regulation of cell shape (GO:0008360), regulation of cell projection organization (GO:0031344), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of GTPase activity (GO:0043547), regulation of bone resorption (GO:0045124), photoreceptor cell maintenance (GO:0045494), positive regulation of phagocytosis (GO:0050766), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of filopodium assembly (GO:0051491), negative regulation of stress fiber assembly (GO:0051497), regulation of endocytosis (GO:0030100), positive regulation of cellular component organization (GO:0051130)

GO Molecular Function (6): GTPase activator activity (GO:0005096), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), zinc ion binding (GO:0008270), type 1 angiotensin receptor binding (GO:0031702), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (16): ruffle (GO:0001726), podosome (GO:0002102), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), early endosome (GO:0005769), multivesicular body (GO:0005771), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), extrinsic component of plasma membrane (GO:0019897), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-6 pathways:

CategoryPathways
RHO GTPase cycle3
Signal Transduction2
Signaling by PTK61
Signaling by Rho GTPases, Miro GTPases and RHOBTB31
Signaling by Non-Receptor Tyrosine Kinases1
Signaling by Rho GTPases1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure5
regulation of cellular component organization3
actin cytoskeleton organization2
GTPase activity2
cytoplasm2
endomembrane system2
Golgi apparatus subcompartment2
receptor recycling1
regulation of receptor recycling1
positive regulation of macromolecule metabolic process1
positive regulation of signaling1
receptor internalization1
regulation of receptor-mediated endocytosis1
supramolecular fiber organization1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
regulation of cell morphogenesis1
regulation of biological quality1
cell projection organization1
regulation of actin filament-based process1
regulation of cytoskeleton organization1
regulation of GTPase activity1
positive regulation of hydrolase activity1
bone resorption1
regulation of bone remodeling1
retina homeostasis1
multicellular organismal process1
phagocytosis1
positive regulation of endocytosis1
regulation of phagocytosis1
small GTPase-mediated signal transduction1
regulation of intracellular signal transduction1
filopodium assembly1
regulation of filopodium assembly1
positive regulation of plasma membrane bounded cell projection assembly1
negative regulation of actin filament bundle assembly1
stress fiber assembly1

Protein interactions and networks

STRING

1120 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ARAP1ANK1P16157718
ARAP1RAB13P51153687
ARAP1ANK2Q01484685
ARAP1ANK3Q12955682
ARAP1PLEK2Q9NYT0657
ARAP1PLEKP08567653
ARAP1AGTRAPQ6RW13610
ARAP1SH3KBP1Q96B97610
ARAP1STARD10Q9Y365606
ARAP1MTNR1BP49286599
ARAP1CDKAL1Q5VV42593
ARAP1SLC30A8Q8IWU4577
ARAP1ZBED3Q96IU2575
ARAP1KLF14Q8TD94573
ARAP1C2CD4AQ8NCU7572

IntAct

60 interactions, top by confidence:

ABTypeScore
GRB2WIPF3psi-mi:“MI:0914”(association)0.730
NCK2SH3PXD2Bpsi-mi:“MI:0914”(association)0.640
SH3KBP1USP27Xpsi-mi:“MI:0914”(association)0.640
CAPZBCNOT1psi-mi:“MI:0914”(association)0.640
CAPZA2CNOT1psi-mi:“MI:0914”(association)0.640
TNFRSF10AARAP1psi-mi:“MI:0915”(physical association)0.540
TNFRSF10AARAP1psi-mi:“MI:0403”(colocalization)0.540
GRB2ARHGEF35psi-mi:“MI:0914”(association)0.530
CRKARHGAP42psi-mi:“MI:0914”(association)0.530
NCK1SH3PXD2Bpsi-mi:“MI:0914”(association)0.530
CAPZA1CNOT1psi-mi:“MI:0914”(association)0.530
GRB2SH3PXD2Bpsi-mi:“MI:0914”(association)0.530
VCAM1PSMD11psi-mi:“MI:0914”(association)0.530
XRCC6ARAP1psi-mi:“MI:0915”(physical association)0.510

BioGRID (73): ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-MS), ARAP1 (Affinity Capture-RNA), ARAP1 (Affinity Capture-RNA), SH3KBP1 (Reconstituted Complex), SH3KBP1 (Co-crystal Structure)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, D3ZBP4, E2RDP2, F1MH07, O08644, O75038, O75064, O75636, P0C0K7, P0DPD7, P0DPE0, P0DPE1, P52824, Q00653, Q0IID2, Q1LWV7, Q3SYT1, Q3U1Y4, Q4KM32, Q4R380, Q5NCQ5, Q5RKI3, Q62137, Q684M2, Q68DD2, Q6ZSI9, Q86TL0, Q86XP0, Q8BGV9, Q8BX80, Q8C9V1, Q8NFF5, Q8NFI3, Q8R5G7, Q8TDZ2, Q8VDP3, Q8WWN8, Q91ZJ0

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

3 interactions.

AEffectBMechanism
ARAP1“down-regulates activity”RAC1“gtpase-activating protein”
ARAP1“down-regulates activity”CDC42“gtpase-activating protein”
PTK6“up-regulates activity”ARAP1phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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:

PathwayPartnersFoldFDR
RHO GTPases Activate WASPs and WAVEs544.1×1e-05
FCGR3A-mediated phagocytosis631.2×7e-06
Regulation of actin dynamics for phagocytic cup formation630.7×7e-06
Clathrin-mediated endocytosis614.2×3e-04
CDC42 GTPase cycle510.0×6e-03
RAC1 GTPase cycle58.5×8e-03
Membrane Trafficking66.2×1e-02
Vesicle-mediated transport65.8×1e-02

GO biological processes:

GO termPartnersFoldFDR
actin cytoskeleton organization610.8×2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance238
Likely benign10
Benign6

Top pathogenic / likely-pathogenic (0)

SpliceAI

6826 predictions. Top by Δscore:

VariantEffectΔscore
11:72686040:A:ACdonor_gain1.0000
11:72686041:C:CCdonor_gain1.0000
11:72686041:CAGA:Cdonor_gain1.0000
11:72686188:CATG:Cacceptor_gain1.0000
11:72686190:TG:Tacceptor_gain1.0000
11:72688449:GCTTA:Gdonor_loss1.0000
11:72688450:CTTA:Cdonor_loss1.0000
11:72688451:TTA:Tdonor_loss1.0000
11:72688452:TA:Tdonor_loss1.0000
11:72688453:A:Cdonor_loss1.0000
11:72688454:C:Tdonor_loss1.0000
11:72688535:ACTC:Aacceptor_loss1.0000
11:72688536:CT:Cacceptor_gain1.0000
11:72688536:CTCTG:Cacceptor_loss1.0000
11:72688538:C:CCacceptor_gain1.0000
11:72688543:G:Cacceptor_gain1.0000
11:72693318:CACTT:Cdonor_loss1.0000
11:72693319:ACTTA:Adonor_loss1.0000
11:72693320:CTTA:Cdonor_loss1.0000
11:72693321:TTA:Tdonor_loss1.0000
11:72693322:TA:Tdonor_loss1.0000
11:72693323:AC:Adonor_gain1.0000
11:72693323:ACCC:Adonor_loss1.0000
11:72693324:C:CGdonor_loss1.0000
11:72693324:CC:Cdonor_gain1.0000
11:72693802:CGCT:Cacceptor_gain1.0000
11:72693804:CT:Cacceptor_gain1.0000
11:72693806:C:CCacceptor_gain1.0000
11:72694978:ACC:Adonor_loss1.0000
11:72694978:ACCTG:Adonor_gain1.0000

AlphaMissense

9381 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:72687465:A:GW1387R1.000
11:72687465:A:TW1387R1.000
11:72695069:A:GL1202P1.000
11:72695746:A:GL1131P1.000
11:72697053:C:AK1032N1.000
11:72697053:C:GK1032N1.000
11:72697172:G:TR993S1.000
11:72687689:A:GW1374R0.999
11:72687689:A:TW1374R0.999
11:72693374:C:GR1302P0.999
11:72693802:C:GR1233P0.999
11:72695818:G:TA1107E0.999
11:72695821:A:GL1106P0.999
11:72695835:C:AM1101I0.999
11:72695835:C:GM1101I0.999
11:72695835:C:TM1101I0.999
11:72695836:A:GM1101T0.999
11:72695841:G:CN1099K0.999
11:72695841:G:TN1099K0.999
11:72695863:A:TV1092D0.999
11:72696998:A:GW1051R0.999
11:72696998:A:TW1051R0.999
11:72697042:C:GR1036P0.999
11:72697055:T:CK1032E0.999
11:72697057:A:GL1031P0.999
11:72697069:A:TV1027D0.999
11:72697162:C:TG996E0.999
11:72697163:C:AG996W0.999
11:72697171:C:GR993P0.999
11:72697175:A:CY992D0.999

dbSNP variants (sampled 300 via entrez): RS1000050264 (11:72715892 G>T), RS1000112103 (11:72712890 C>T), RS1000130887 (11:72731020 G>C), RS1000182848 (11:72713961 T>C,G), RS1000208604 (11:72713030 C>A,G,T), RS1000289998 (11:72685471 C>T), RS1000311847 (11:72737862 G>A), RS1000325507 (11:72685161 A>G), RS1000370584 (11:72750105 C>T), RS1000387140 (11:72725229 C>A), RS1000465900 (11:72729452 G>C), RS1000549737 (11:72689484 C>A,G), RS1000618363 (11:72736019 A>G), RS1000656032 (11:72714113 C>T), RS1000685107 (11:72737618 C>T)

Disease associations

OMIM: gene MIM:606646 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

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

HPOTerm
HP:0000717Autism

GWAS associations

43 associations (top):

StudyTraitp-value
GCST000712_4Type 2 diabetes1.000000e-22
GCST001212_1Proinsulin levels3.000000e-102
GCST001454_7Rheumatoid arthritis6.000000e-10
GCST001527_2Fasting blood glucose (BMI interaction)2.000000e-14
GCST002352_9Type 2 diabetes1.000000e-07
GCST002691_1Alloimmunization response to red blood cell transfusion in sickle cell anemia7.000000e-07
GCST002783_445Body mass index4.000000e-06
GCST002783_521Body mass index9.000000e-06
GCST003400_4Type 2 diabetes3.000000e-06
GCST004575_4Acute insulin response4.000000e-06
GCST004599_23Mean platelet volume7.000000e-15
GCST004894_110Type 2 diabetes3.000000e-17
GCST004894_6Type 2 diabetes1.000000e-13
GCST004904_140Body mass index1.000000e-08
GCST005047_103Type 2 diabetes9.000000e-09
GCST005047_18Type 2 diabetes2.000000e-10
GCST005186_7Fasting blood glucose2.000000e-09
GCST005414_2Type 2 diabetes2.000000e-06
GCST005440_3Alcohol dependence symptom count9.000000e-06
GCST006801_9Type 2 diabetes5.000000e-06
GCST006867_99Type 2 diabetes9.000000e-25
GCST007515_35Type 2 diabetes5.000000e-08
GCST007516_15Type 2 diabetes (adjusted for BMI)5.000000e-10
GCST007518_23Type 2 diabetes (adjusted for BMI)2.000000e-09
GCST007847_79Type 2 diabetes1.000000e-11
GCST007899_15Fasting blood glucose2.000000e-06
GCST007923_50Medication use (drugs used in diabetes)3.000000e-11
GCST007954_11Glycated hemoglobin levels7.000000e-09
GCST008109_2Fasting blood proinsulin levels6.000000e-45
GCST008151_97Waist circumference1.000000e-06

EFO canonical traits (11, from GWAS)

EFO IDTrait name
EFO:0004467insulin measurement
EFO:0004340body mass index
EFO:0006802response to red blood cell transfusion
EFO:0006804alloimmunization
EFO:0006831acute insulin response measurement
EFO:0007835alcohol dependence measurement
EFO:0009924Drugs used in diabetes use measurement
EFO:0004541HbA1c measurement
EFO:0007789BMI-adjusted waist circumference
EFO:0009695household income
EFO:0007800body fat percentage

MeSH disease descriptors (1)

DescriptorNameTree numbers
D001321Autistic DisorderF03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs11603334ARAP10.000

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, increases expression, decreases reaction, increases abundance3
Ozoneincreases abundance, affects expression, increases expression, affects cotreatment, decreases expression (+1 more)3
sodium arseniteaffects cotreatment, decreases expression, increases abundance, increases expression2
Air Pollutantsaffects cotreatment, decreases expression, increases abundance, increases oxidation, affects expression2
Arsenicaffects methylation, affects cotreatment, decreases expression, increases abundance, increases expression2
GSK-J4increases expression1
FR900359increases phosphorylation1
ginger extractdecreases expression, decreases reaction, increases abundance1
2,4,6-tribromophenoldecreases expression1
triphenyl phosphateaffects expression1
alpha-pineneincreases oxidation, increases abundance, affects cotreatment, decreases expression1
salinomycindecreases expression1
decabromobiphenyl etherdecreases expression1
dimethylselenideincreases expression, increases oxidation1
tetrabromobisphenol Adecreases expression1
perfluorooctanoic aciddecreases expression1
muconaldehydedecreases expression1
methacrylaldehydeaffects cotreatment, decreases expression, increases oxidation, increases abundance1
di-n-butylphosphoric acidaffects expression1
entinostatincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
2,2’,4,4’-tetrabromodiphenyl etherdecreases expression1
pentabrominated diphenyl ether 100decreases expression1
hexabrominated diphenyl ether 153decreases expression1
bisphenol Sdecreases methylation1
jinfukangaffects cotreatment, increases expression1
LDN 193189affects cotreatment, increases expression1
(+)-JQ1 compounddecreases expression1
Zoledronic Aciddecreases expression1
Acroleindecreases expression, increases oxidation, increases abundance, affects cotreatment1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00211796PHASE4COMPLETEDDivalproex Sodium ER in Adult Autism
NCT00391261PHASE4COMPLETEDAn Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747PHASE4COMPLETEDMinocycline to Treat Childhood Regressive Autism
NCT00576732PHASE4COMPLETEDA Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753PHASE4COMPLETEDAtomoxetine, Placebo and Parent Management Training in Autism
NCT01028820PHASE4COMPLETEDFMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383PHASE4UNKNOWNTreatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865PHASE4COMPLETEDA Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700PHASE4COMPLETEDMilnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200PHASE4COMPLETEDOmega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977PHASE4UNKNOWNStudy to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952PHASE4COMPLETEDMethylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925PHASE4UNKNOWNAn Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467PHASE4COMPLETEDMultisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565PHASE4COMPLETEDDose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574PHASE4COMPLETEDNeural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629PHASE4COMPLETEDPromoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646PHASE4COMPLETEDEvaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431PHASE4COMPLETEDImproving Driving in Young People With Autism Spectrum Disorders
NCT03757585PHASE4COMPLETEDNatural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353PHASE4COMPLETEDPragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656PHASE4COMPLETEDBiomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245PHASE4UNKNOWNSafety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339PHASE4RECRUITINGAWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052PHASE4TERMINATEDA Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665PHASE4RECRUITINGThe TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697PHASE4COMPLETEDPilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804PHASE4COMPLETEDPilot RCT Using Homeopathic Medicines in ASD
NCT07439042PHASE4NOT_YET_RECRUITINGBuspirone for Anxiety in Autistic Youth
NCT00036231PHASE3TERMINATEDSynthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244PHASE3COMPLETEDSynthetic Human Secretin in Children With Autism
NCT00065884PHASE3UNKNOWNValproate Response in Aggressive Autistic Adolescents
NCT00065962PHASE3COMPLETEDSecretin for the Treatment of Autism
NCT00252603PHASE3COMPLETEDGalantamine Versus Placebo in Childhood Autism
NCT00346736PHASE3COMPLETEDUse of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248PHASE3COMPLETEDRandomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352PHASE3COMPLETEDUse of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329PHASE3COMPLETEDRandomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173PHASE3COMPLETEDEffectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346PHASE3COMPLETEDA Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot