ARAP2

Summary

ARAP2 (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2, HGNC:16924) is a protein-coding gene on chromosome 4p14, encoding Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (Q8WZ64). 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 ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics.

Source: NCBI Gene 116984 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 306 total — 1 pathogenic
• MANE Select transcript: NM_015230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16924
Approved symbol	ARAP2
Name	ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	PARX
Ensembl gene	ENSG00000047365
Ensembl biotype	protein_coding
OMIM	606645
Entrez	116984

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000303965, ENST00000503225, ENST00000503904, ENST00000505837, ENST00000506189, ENST00000508066, ENST00000511416, ENST00000512804, ENST00000513032, ENST00000905954, ENST00000942324

RefSeq mRNA: 1 — MANE Select: NM_015230 NM_015230

CCDS: CCDS3441

Canonical transcript exons

ENST00000303965 — 33 exons

Exon	Start	End
ENSE00000709041	36114170	36114287
ENSE00000709042	36117061	36117135
ENSE00000709043	36119650	36119718
ENSE00000709049	36147548	36147746
ENSE00000709050	36148405	36148507
ENSE00000709053	36159331	36159505
ENSE00000709054	36160459	36160641
ENSE00001073473	36066004	36068278
ENSE00001073477	36073689	36073823
ENSE00001073479	36083368	36083450
ENSE00001171773	36080216	36080279
ENSE00001171783	36082251	36082286
ENSE00001171791	36091881	36092020
ENSE00001171800	36107565	36107693
ENSE00001171808	36121179	36121326
ENSE00001171818	36124862	36124967
ENSE00001171830	36128533	36128745
ENSE00001171837	36133226	36133389
ENSE00001171843	36147296	36147359
ENSE00001402822	36244179	36244514
ENSE00003480890	36210390	36210743
ENSE00003481107	36214422	36214480
ENSE00003500065	36161465	36161550
ENSE00003509344	36177827	36178005
ENSE00003526820	36193578	36193647
ENSE00003539528	36150900	36151044
ENSE00003555495	36166932	36167047
ENSE00003605342	36213243	36213319
ENSE00003607496	36158730	36158864
ENSE00003629139	36164914	36165113
ENSE00003662365	36187451	36187571
ENSE00003667241	36212396	36212487
ENSE00003682967	36228582	36229645

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 97.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7272 / max 952.6353, expressed in 1062 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51765	5.4820	927
51769	1.9422	594
51756	1.6870	225
51762	1.3145	404
51757	1.2696	292
51759	0.6248	267
51755	0.5182	182
51761	0.5087	232
51766	0.5062	221
51770	0.4794	247

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.62	gold quality
secondary oocyte	CL:0000655	97.23	gold quality
corpus callosum	UBERON:0002336	96.97	gold quality
gingival epithelium	UBERON:0001949	96.77	gold quality
cranial nerve II	UBERON:0000941	96.17	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.14	gold quality
gingiva	UBERON:0001828	95.98	gold quality
esophagus squamous epithelium	UBERON:0006920	95.74	gold quality
amniotic fluid	UBERON:0000173	95.55	gold quality
squamous epithelium	UBERON:0006914	95.38	gold quality
medial globus pallidus	UBERON:0002477	95.05	gold quality
middle temporal gyrus	UBERON:0002771	94.90	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.89	gold quality
germinal epithelium of ovary	UBERON:0001304	94.75	gold quality
inferior olivary complex	UBERON:0002127	94.74	gold quality
palpebral conjunctiva	UBERON:0001812	94.63	gold quality
globus pallidus	UBERON:0001875	94.59	gold quality
upper leg skin	UBERON:0004262	94.07	gold quality
tongue squamous epithelium	UBERON:0006919	93.69	gold quality
postcentral gyrus	UBERON:0002581	93.42	gold quality
oocyte	CL:0000023	93.36	gold quality
parietal lobe	UBERON:0001872	92.58	gold quality
epithelium of nasopharynx	UBERON:0001951	92.58	gold quality
nasopharynx	UBERON:0001728	92.57	gold quality
primary visual cortex	UBERON:0002436	92.43	gold quality
entorhinal cortex	UBERON:0002728	91.83	gold quality
superior frontal gyrus	UBERON:0002661	91.62	gold quality
lateral globus pallidus	UBERON:0002476	91.49	gold quality
epithelium of esophagus	UBERON:0001976	91.39	gold quality
occipital lobe	UBERON:0002021	91.35	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	93.33
E-CURD-122	yes	29.04
E-MTAB-6678	yes	22.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

170 targeting ARAP2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 6)

• ARAP2 is an Arf6GAP that functions downstream of RhoA to regulate focal adhesion dynamics. (PMID:17077126)
• Our findings indicate that ARAP2 promotes InlB-mediated entry of Listeria monocytogenes in part, by antagonizing the host GTPase Arf6. (PMID:20823205)
• ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology (PMID:23295182)
• ACAP1 and ARAP2 each colocalize with Arf6 but they did not colocalize with each other and have opposing effects on focal adhesions. (PMID:25225293)
• These results highlight an Arf GAP-independent function of ARAP2 in regulating Akt activity. (PMID:30144359)
• The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition. (PMID:35842667)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arap2	ENSMUSG00000037999
rattus_norvegicus	Arap2	ENSRNOG00000056826

Paralogs (28): 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), 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 2 — Q8WZ64 (reviewed: Q8WZ64)

Alternative names: Centaurin-delta-1, Protein PARX

All UniProt accessions (3): D6RAD6, D6RC39, Q8WZ64

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.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in brain, thymus, lymph node, thyroid, spinal cord, trachea, heart, skeletal muscle, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes.

RefSeq proteins (1): NP_056045* (*=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
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, PF00536, PF00620, PF00788, PF01412

UniProt features (41 total): domain 9, strand 8, helix 7, sequence variant 3, turn 3, region of interest 2, compositionally biased region 2, modified residue 2, sequence conflict 2, chain 1, zinc finger region 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1X40	SOLUTION NMR
2COD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WZ64-F1	67.42	0.31

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): 1151 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (2): 77, 1632

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: 302 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, JAEGER_METASTASIS_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MEF2_02, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GATA6_01, AAAGGGA_MIR204_MIR211

GO Biological Process (3): signal transduction (GO:0007165), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of GTPase activity (GO:0043547)

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

GO Cellular Component (1): cytoplasm (GO:0005737)

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
GTPase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	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
enzyme activator activity	1
GTPase regulator activity	1
anion binding	1
phosphatidylinositol phosphate binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARAP2	RAB13	P51153	711
ARAP2	PLEK2	Q9NYT0	615
ARAP2	PLEK	P08567	611
ARAP2	ANK3	Q12955	605
ARAP2	ANK1	P16157	599
ARAP2	ANK2	Q01484	595
ARAP2	GIT2	Q14161	518
ARAP2	GIT1	Q9Y2X7	489
ARAP2	ASAP1	Q9ULH1	481
ARAP2	RAP1GDS1	P52306	455
ARAP2	ASAP3	Q8TDY4	453
ARAP2	AGFG2	O95081	451
ARAP2	ARF6	P26438	450
ARAP2	ARHGAP20	Q9P2F6	441
ARAP2	APBB1IP	Q7Z5R6	410

IntAct

23 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
Dlg4	ARAP2	psi-mi:“MI:0407”(direct interaction)	0.440
ARAP2	KRT17	psi-mi:“MI:0915”(physical association)	0.400
APPL2	SOS1	psi-mi:“MI:0914”(association)	0.350
ARAP2	INPPL1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
FYN	ARAP2	psi-mi:“MI:0915”(physical association)	0.000
ARAP2		psi-mi:“MI:0915”(physical association)	0.000
ARAP2	malK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): ARAP2 (Co-fractionation), ARAP2 (Proximity Label-MS), ARAP2 (Affinity Capture-RNA), ARAP2 (Proximity Label-MS), ARAP2 (Proximity Label-MS), ARAP2 (Affinity Capture-MS), ARAP2 (FRET), ARAP2 (FRET), ARAP2 (FRET), ARAP2 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), LIN7C (Affinity Capture-MS), ARHGAP24 (Affinity Capture-MS), ARAP2 (Proximity Label-MS), ARAP2 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8HU22, A1A5R8, A8K979, B8A5Y1, E1BB03, F6UH96, O75113, P62283, P62285, P62286, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, Q08AX9, Q3MHN7, Q3US16, Q5BKS4, Q5HZL1, Q5XKL5, Q5ZIX8, Q5ZLE9, Q64702, Q68FF0, Q6A037, Q6IE81, Q6NQ79, Q6NSI8, Q6NZP1, Q6PCM1, Q8BMI4, Q8BVE8, Q8BZ05, Q8CJ27

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P40529, P40956, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q3MID3, Q3UHD9, Q4KLN7, Q4LDD4, Q4R4C9, Q5EA00, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2, Q5VUJ5, Q5VW22, Q5W7F2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ARAP2	“down-regulates activity”	RHOA	“gtpase-activating protein”
ARAP2	“down-regulates activity”	RAC1	“gtpase-activating protein”
ARAP2	“down-regulates activity”	CDC42	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	333.1×	2e-15
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	293.9×	3e-15
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	293.9×	3e-15
Activation of BH3-only proteins	7	217.2×	3e-14
RHO GTPases activate PKNs	7	138.8×	9e-13
Intrinsic Pathway for Apoptosis	7	128.1×	1e-12
FOXO-mediated transcription	5	105.0×	1e-08
SARS-CoV-1-host interactions	7	76.9×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	114.5×	7e-08
intracellular protein localization	7	45.8×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	259
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062750	GRCh37/hg19 4p16.3-11(chr4:68345-49089361)x3	Pathogenic

SpliceAI

6257 predictions. Top by Δscore:

Variant	Effect	Δscore
4:36082293:C:CT	acceptor_gain	1.0000
4:36082295:C:CT	acceptor_gain	1.0000
4:36082296:A:AC	acceptor_gain	1.0000
4:36082296:A:C	acceptor_gain	1.0000
4:36083352:C:A	donor_gain	1.0000
4:36083362:CTTTA:C	donor_loss	1.0000
4:36083363:TTTA:T	donor_loss	1.0000
4:36083364:TTACC:T	donor_loss	1.0000
4:36083365:TACC:T	donor_loss	1.0000
4:36083366:A:T	donor_loss	1.0000
4:36083367:C:CA	donor_loss	1.0000
4:36083446:CTACT:C	acceptor_gain	1.0000
4:36083447:TACT:T	acceptor_gain	1.0000
4:36083449:CT:C	acceptor_gain	1.0000
4:36083451:C:CC	acceptor_gain	1.0000
4:36091888:T:TA	donor_gain	1.0000
4:36091944:ATTT:A	donor_gain	1.0000
4:36092016:CCGGT:C	acceptor_gain	1.0000
4:36092017:CGGT:C	acceptor_gain	1.0000
4:36092017:CGGTC:C	acceptor_gain	1.0000
4:36107564:CCA:C	donor_gain	1.0000
4:36107604:TCACC:T	donor_gain	1.0000
4:36107607:C:CT	donor_gain	1.0000
4:36107690:CGCT:C	acceptor_gain	1.0000
4:36107691:GCT:G	acceptor_gain	1.0000
4:36107692:CT:C	acceptor_gain	1.0000
4:36107692:CTC:C	acceptor_gain	1.0000
4:36107693:TCT:T	acceptor_gain	1.0000
4:36107694:C:CC	acceptor_gain	1.0000
4:36107694:CTGT:C	acceptor_loss	1.0000

AlphaMissense

11293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:36160602:A:G	W767R	1.000
4:36160602:A:T	W767R	1.000
4:36160625:C:A	G759V	1.000
4:36161483:C:A	W747C	1.000
4:36161483:C:G	W747C	1.000
4:36161484:C:G	W747S	1.000
4:36161485:A:G	W747R	1.000
4:36161485:A:T	W747R	1.000
4:36161496:T:A	D743V	1.000
4:36161496:T:C	D743G	1.000
4:36161496:T:G	D743A	1.000
4:36161497:C:G	D743H	1.000
4:36161499:A:G	M742T	1.000
4:36161501:T:A	K741N	1.000
4:36161501:T:G	K741N	1.000
4:36161503:T:C	K741E	1.000
4:36161505:A:G	L740P	1.000
4:36161507:A:C	S739R	1.000
4:36161507:A:T	S739R	1.000
4:36161509:T:G	S739R	1.000
4:36161540:T:A	R728S	1.000
4:36161540:T:G	R728S	1.000
4:36161541:C:G	R728T	1.000
4:36164918:A:C	C723W	1.000
4:36164920:A:G	C723R	1.000
4:36164927:A:C	C720W	1.000
4:36164928:C:T	C720Y	1.000
4:36164929:A:G	C720R	1.000
4:36164957:C:A	W710C	1.000
4:36164957:C:G	W710C	1.000

dbSNP variants (sampled 300 via entrez): RS1000013071 (4:36231729 G>A), RS1000016546 (4:36013927 G>A), RS10000381 (4:36092481 T>C), RS1000065299 (4:36216554 T>G), RS1000134461 (4:36143717 T>C), RS1000149335 (4:36136062 T>C), RS1000158154 (4:36095550 A>G), RS1000160300 (4:36007932 T>C), RS10001711 (4:36155425 G>T), RS1000173745 (4:36089439 T>C), RS1000181000 (4:36047862 A>G), RS1000181463 (4:36079725 T>C), RS1000199522 (4:36008453 A>C,T), RS1000201343 (4:36136445 A>C,G), RS1000204493 (4:36062308 T>C)

Disease associations

OMIM: gene MIM:606645 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000211_5	Response to TNF antagonist treatment	4.000000e-06
GCST001663_10	Amyotrophic lateral sclerosis (age of onset)	5.000000e-07
GCST001762_117	Obesity-related traits	3.000000e-06
GCST001762_303	Obesity-related traits	6.000000e-06
GCST001762_94	Obesity-related traits	6.000000e-07
GCST002579_10	Heschl’s gyrus morphology	4.000000e-06
GCST002759_24	Motion sickness	2.000000e-09
GCST003124_17	Mild influenza (H1N1) infection	1.000000e-09
GCST003124_20	Mild influenza (H1N1) infection	2.000000e-08
GCST003124_7	Mild influenza (H1N1) infection	3.000000e-10
GCST003125_1	Influenza A (H1N1) infection	5.000000e-09
GCST003854_2	Gut microbiota (functional units)	1.000000e-08
GCST006627_84	Diastolic blood pressure	5.000000e-09
GCST006993_5	Hippocampal volume in Alzheimer’s disease dementia	4.000000e-07
GCST007327_73	Smoking status (ever vs never smokers)	4.000000e-08
GCST009602_64	Metabolic syndrome	5.000000e-09
GCST010396_192	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST011011_55	Youthful appearance (self-reported)	5.000000e-11
GCST011703_64	Smoking initiation	3.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004847	age at onset
EFO:0003940	physical activity
EFO:0006928	motion sickness
EFO:1001488	influenza A (H1N1)
EFO:0007874	gut microbiome measurement
EFO:0006336	diastolic blood pressure
EFO:0005035	hippocampal volume
EFO:0004318	smoking behavior
EFO:0000195	metabolic syndrome
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs437943	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs437943	ARAP2	3	0.00	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression, affects cotreatment, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
mercuric bromide	increases expression, affects cotreatment, affects expression	2
perfluorooctane sulfonic acid	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Lipopolysaccharides	decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, affects expression, increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
coenzyme Q10	decreases reaction, increases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
3-nitrobenzanthrone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects expression, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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