RAP2A

Summary

RAP2A (RAP2A, member of RAS oncogene family, HGNC:9861) is a protein-coding gene on chromosome 13q32.1, encoding Ras-related protein Rap-2a (P10114). Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form.

Enables GTPase activity; guanyl ribonucleotide binding activity; and magnesium ion binding activity. Involved in several processes, including microvillus assembly; positive regulation of protein autophosphorylation; and regulation of dendrite morphogenesis. Acts upstream of or within establishment of protein localization. Located in plasma membrane and recycling endosome membrane. Is active in Schaffer collateral - CA1 synapse.

Source: NCBI Gene 5911 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_021033

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9861
Approved symbol	RAP2A
Name	RAP2A, member of RAS oncogene family
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	K-REV
Ensembl gene	ENSG00000125249
Ensembl biotype	protein_coding
OMIM	179540
Entrez	5911

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000245304, ENST00000476869

RefSeq mRNA: 1 — MANE Select: NM_021033 NM_021033

CCDS: CCDS9485

Canonical transcript exons

ENST00000245304 — 2 exons

Exon	Start	End
ENSE00000853869	97434169	97434784
ENSE00001128147	97464205	97469128

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1003 / max 134.7358, expressed in 1768 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135739	11.3186	1692
135738	5.7817	1630

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.16	gold quality
buccal mucosa cell	CL:0002336	99.13	gold quality
medial globus pallidus	UBERON:0002477	99.02	gold quality
globus pallidus	UBERON:0001875	98.95	gold quality
superior vestibular nucleus	UBERON:0007227	98.95	gold quality
subthalamic nucleus	UBERON:0001906	98.87	gold quality
parietal lobe	UBERON:0001872	98.83	gold quality
middle temporal gyrus	UBERON:0002771	98.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.75	gold quality
inferior vagus X ganglion	UBERON:0005363	98.74	gold quality
postcentral gyrus	UBERON:0002581	98.73	gold quality
tongue squamous epithelium	UBERON:0006919	98.73	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.71	gold quality
cranial nerve II	UBERON:0000941	98.68	gold quality
substantia nigra pars compacta	UBERON:0001965	98.60	gold quality
lateral globus pallidus	UBERON:0002476	98.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.40	gold quality
trigeminal ganglion	UBERON:0001675	98.39	gold quality
cortical plate	UBERON:0005343	98.33	gold quality
ventral tegmental area	UBERON:0002691	98.31	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.12	gold quality
orbitofrontal cortex	UBERON:0004167	98.03	gold quality
entorhinal cortex	UBERON:0002728	97.97	gold quality
medulla oblongata	UBERON:0001896	97.90	gold quality
superior frontal gyrus	UBERON:0002661	97.89	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.72	gold quality
body of tongue	UBERON:0011876	97.67	gold quality
pharyngeal mucosa	UBERON:0000355	97.62	gold quality
tongue	UBERON:0001723	97.34	gold quality
endothelial cell	CL:0000115	97.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

269 targeting RAP2A, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666

Literature-anchored findings (GeneRIF, showing 32)

• Rap2 enhanced MAP4K4-induced activation of JNK (PMID:14966141)
• TNIK is a specific effector of Rap2 to regulate actin cytoskeleton (PMID:15342639)
• RGS14 activity towards heterotrimeric G-proteins, as either a GAP or a guanine nucleotide dissociation inhibitor, was unaffected by Rap binding. (PMID:16246175)
• RT-PCR analysis of mRNA extracted from highly purified reticulocytes confirmed the expression of Rap2b, but not Rap2a, Rap2c, Rap1a or Rap1b. (PMID:16540189)
• A study that demonstrated the engagement of beta2 integrins on human neutrophils increased the levels of GTP-bound Rap1 and Rap2 is presented. (PMID:16963453)
• interaction surfaces in RAPL-Rap1 and RAPL-Rap2 complexes are different and that a single residue in the switch I region of Rap proteins (residue 39) contributes considerably to the different kinetics of these protein-protein interactions. (PMID:17716979)
• Rap2 is involved in androgen-mediated transcriptional and growth responses of human prostate cancer cells. (PMID:17918750)
• Study presents evidence of fewer spines and reduced signaling in Rap2 transgenic mice, consistent with an inhibitory role for Rap2 at synapses. (PMID:18701680)
• The beta2 integrin-dependent exocytosis of specific and gelatinase B-containing granules is responsible for the translocation of Rap1 and Rap2 to the plasma membrane in human neutrophils. (PMID:18789886)
• analyzed residues that allow RasGEF1 proteins to discriminate between Rap1 and Rap2, and identified Phe39 in the switch I region of Rap2 as a specificity residue. (PMID:19645719)
• Rap2A and TNIK control brush border formation by apical recruitment of MST4 and the subsequent phosphorylation of Ezrin (PMID:22797597)
• endothelial barrier resistance is determined by the combined antagonistic actions of Rap1 and Rap2 (PMID:23469100)
• downregulation of Rap2a promoted glioma migration and invasion, and raised the phosphorylation level of AKT (PMID:24293123)
• the role of Rap2a in carcinogenesis (PMID:25248704)
• Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases. (PMID:25533468)
• The ectopic expression of Rap2a enhances the migration and invasive ability of cancer cells and increases activities of matrix metalloproteinase MMP2 and MMP9. (PMID:25728512)
• present review mainly focused on recent studies on the functional and physical interactions between Rap2 and its effectors. We also speculated on the relevance of these pathways to tumorigenesis (PMID:25980814)
• Single nucleotide polymorphism in RAP2A gene is associated with Peripheral Arterial Disease. (PMID:26488411)
• The small GTPase Ras-related protein 2 (Rap2) was found to bind ArrB1 under resting conditions but dissociated upon formyl-Met-Leu-Phe stimulation. (PMID:27493245)
• Nedd4-1 inhibited Rap2a activity, and promoted the migration and invasion of glioma cells. (PMID:28405688)
• These findings indicate that Rap2a promotes renal cell carcinoma metastasis and may serve as a candidate renal cell carcinoma prognostic marker and a potential therapeutic target. (PMID:28747626)
• Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum. (PMID:29352039)
• The phosphorylation also produces an increase in GAP activity toward Rap2 , an effect not produced by either kinase alone. (PMID:30049443)
• RAP2 mediates mechanoresponses of the Hippo pathway; RAP2 is a molecular switch in mechanotransduction, thereby defining a mechanosignalling pathway from extracellular matrix stiffness to the nucleus (PMID:30135582)
• Abnormal expression of Rap2A as a prognostic marker for human breast cancer. (PMID:33015796)
• lncRNA FLVCR1AS1 drives colorectal cancer progression via modulation of the miR381/RAP2A axis. (PMID:33313944)
• RAP2A promotes apoptosis resistance of hepatocellular carcinoma cells via the mTOR pathway. (PMID:34018090)
• Tumor suppressive role of miR-33a-5p in pancreatic ductal adenocarcinoma cells by directly targeting RAP2A. (PMID:34090323)
• Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation. (PMID:35054818)
• Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration. (PMID:35293963)
• TGF-beta1-induced RAP2 regulates invasion in pancreatic cancer. (PMID:35538031)
• Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation. (PMID:38574891)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rap2ab	ENSDARG00000040246
danio_rerio	rap2aa	ENSDARG00000077553
mus_musculus	Rap2a	ENSMUSG00000051615
rattus_norvegicus	Rap2a	ENSRNOG00000083135
caenorhabditis_elegans		WBGENE00004308

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

Ras-related protein Rap-2a — P10114 (reviewed: P10114)

Alternative names: RbBP-30

All UniProt accessions (2): P10114, F6U784

UniProt curated annotations — full annotation on UniProt →

Function. Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and regulates cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.

Subunit / interactions. Interacts (GTP-bound form) with RUNDC3A. Interacts with RGS14; the interaction is GTP-dependent. Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound form preferentially) with TNIK (via the CNH domain); the interaction is direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts with MINK1. Interacts (GTP-bound form preferentially) with MAP4K4. Interacts with cytoskeletal actin.

Subcellular location. Midbody. Cell projection. Lamellipodium membrane. Golgi apparatus. Recycling endosome membrane. Lysosome.

Post-translational modifications. Ubiquitinated; undergoes ‘Lys-63’ monoubiquitination and diubiquitination by NEDD4. Multiple lysine residues are probably modified. Ubiquitination requires TNIK, prevents interaction with effectors and inactivates RAP2A. Ubiquitination by the ECS(RAB40B) complex leads to RAP2A localization to lamellipodia plasma membrane, activation, and regulation of sorting at early endosomes for recycling to the lamellipodia plasma membrane. Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK. (Microbial infection) Glucosylated at Thr-35 by C.difficile toxin TcdA in the colonic epithelium, and by P.sordellii toxin TcsL in the vascular endothelium.

Activity regulation. Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B.

Domain organisation. The effector domain mediates the interaction with RUNDC3A.

Similarity. Belongs to the small GTPase superfamily. Ras family.

RefSeq proteins (1): NP_066361* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041840	Rap2	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (34 total): mutagenesis site 10, strand 6, helix 6, binding site 3, lipid moiety-binding region 3, chain 1, propeptide 1, glycosylation site 1, short sequence motif 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1KAO	X-RAY DIFFRACTION	1.7
3RAP	X-RAY DIFFRACTION	2.2
2RAP	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10114-F1	91.88	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 10–17; 57–61; 116–119

Post-translational modifications (4): 180, 176, 177, 180

Glycosylation sites (1): 35

Mutagenesis-validated functional residues (10):

Position	Phenotype
5	reduced nedd4-dependent ubiquitination; when associated with r-94; r-148 and r-150.
12	dominant active (gtp-bound mutant). 2-fold decrease in gdp dissociation rate constant and gtpase activity. no change in
17	dominant negative (gdp-bound mutant). severely impairs gtp-binding and partial loss of interaction with map4k4, mink1 an
35	decreases affinity for gtp and 3-fold reduction of gtpase activity.
39	loss of rasgef1a- and rasgef1b-mediated gdp to gtp exchange. complete loss of interaction with map4k4, mink1 and tnik, a
94	reduced nedd4-dependent ubiquitination; when associated with r-5; r-148 and r-150.
117	increased binding to rab40c; when associated with r-148 and r-150. increased localization within endolysosomes; when ass
145	imperfect binding of guanyl nucleotides.
148	reduced nedd4-dependent ubiquitination; when associated with r-5; r-94 and r-150. increased binding to rab40c; when asso
150	reduced nedd4-dependent ubiquitination; when associated with r-5; r-94 and r-148. increased binding to rab40c; when asso

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 379 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_DENDRITE_DEVELOPMENT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SYNAPSE_ASSEMBLY, BROWNE_HCMV_INFECTION_8HR_UP, TTTGTAG_MIR520D, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (12): intracellular protein localization (GO:0008104), actin cytoskeleton organization (GO:0030036), positive regulation of cell migration (GO:0030335), negative regulation of cell migration (GO:0030336), Rap protein signal transduction (GO:0032486), establishment of protein localization (GO:0045184), regulation of JNK cascade (GO:0046328), regulation of dendrite morphogenesis (GO:0048814), regulation of synapse assembly (GO:0051963), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), positive regulation of microvillus assembly (GO:1903698), signal transduction (GO:0007165)

GO Molecular Function (8): magnesium ion binding (GO:0000287), GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (18): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), midbody (GO:0030496), lamellipodium membrane (GO:0031258), endolysosome (GO:0036019), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), synaptic membrane (GO:0097060), Schaffer collateral - CA1 synapse (GO:0098685), lysosome (GO:0005764), endosome (GO:0005768), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cell projection (GO:0042995), synapse (GO:0045202), bounding membrane of organelle (GO:0098588)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell migration	2
regulation of cell migration	2
guanyl ribonucleotide binding	2
cytoplasm	2
endomembrane system	2
endosome	2
synapse	2
cytoplasmic vesicle	2
macromolecule localization	1
cytoskeleton organization	1
actin filament-based process	1
positive regulation of cell motility	1
negative regulation of cell motility	1
small GTPase-mediated signal transduction	1
establishment of localization	1
JNK cascade	1
regulation of MAPK cascade	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	1
regulation of biological quality	1
microvillus assembly	1
regulation of microvillus assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

2759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAP2A	TNIK	Q9UKE5	976
RAP2A	ARHGAP29	Q52LW3	952
RAP2A	APOA5	Q6Q788	885
RAP2A	RAPGEF2	Q9Y4G8	874
RAP2A	RAPGEF4	Q8WZA2	865
RAP2A	RAPGEF3	O95398	848
RAP2A	LRPAP1	P30533	832
RAP2A	RUNDC3A	Q59EK9	819
RAP2A	RAPGEF6	Q8TEU7	815
RAP2A	RUNDC3B	Q96NL0	777
RAP2A	SGSM1	Q2NKQ1	752
RAP2A	KRIT1	O00522	727
RAP2A	SGSM2	O43147	716
RAP2A	SGSM3	Q96HU1	713
RAP2A	SIPA1	Q96FS4	705

IntAct

55 interactions, top by confidence:

A	B	Type	Score
RIN1	NRAS	psi-mi:“MI:0914”(association)	0.840
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
RAP2A	RGL1	psi-mi:“MI:0915”(physical association)	0.560
RAP2A	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.560
MINK1	RAP2A	psi-mi:“MI:0915”(physical association)	0.550
EMP3	RAP2A	psi-mi:“MI:0915”(physical association)	0.540
RAP2A	EMP3	psi-mi:“MI:2364”(proximity)	0.540
RAP2A	EMP3	psi-mi:“MI:0915”(physical association)	0.540
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
RAP2C	MAP4K4	psi-mi:“MI:0914”(association)	0.530
	RAP2A	psi-mi:“MI:0915”(physical association)	0.400
RAP2A	LOC303259	psi-mi:“MI:0915”(physical association)	0.400
FNTA	RAP2A	psi-mi:“MI:0915”(physical association)	0.400
RAP2A	Rassf5	psi-mi:“MI:0915”(physical association)	0.370
S1PR1	POTEF	psi-mi:“MI:0914”(association)	0.350
CYP2S1	MPP2	psi-mi:“MI:0914”(association)	0.350
SDC1	ARVCF	psi-mi:“MI:0914”(association)	0.350
VDAC3	HRAS	psi-mi:“MI:0914”(association)	0.350
NCSTN	YES1	psi-mi:“MI:0914”(association)	0.350
MARVELD2	RAP2A	psi-mi:“MI:0914”(association)	0.350
RAP2A	CHEK1	psi-mi:“MI:0914”(association)	0.350
RGL1	TULP3	psi-mi:“MI:0914”(association)	0.350
TRMT6	VPS37C	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): RAP2A (Affinity Capture-RNA), RAP2A (Affinity Capture-RNA), RAP2A (Affinity Capture-RNA), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RAP2A (Affinity Capture-MS), CCT6A (Co-fractionation), DDX39A (Co-fractionation), RAP2A (Co-fractionation), RAP2A (Two-hybrid)

ESM2 similar proteins: A8NU18, D3Z8L7, G4MZY8, G4N1S3, O08989, O14807, O42785, O93856, P01114, P04388, P08647, P0CQ42, P0CQ43, P10114, P10301, P10833, P22126, P22278, P22279, P22280, P28775, P32252, P32253, P32254, P34726, P38976, P51539, P61225, P61226, P61227, P62070, P62071, P70425, P70426, P87018, P97538, Q01387, Q05058, Q06AU2, Q08DI5

Diamond homologs: A1DZY4, A6QP66, A8NU18, C4YKT4, O08989, O14807, O35929, O88667, O93856, O94363, P01119, P03967, P08645, P08647, P0CY32, P10114, P10536, P11233, P11234, P15064, P17609, P22124, P22126, P22278, P22279, P22280, P28775, P32254, P36860, P36863, P48555, P59279, P61105, P61225, P61226, P61227, P62070, P62071, P63320, P63321

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

543 predictions. Top by Δscore:

Variant	Effect	Δscore
13:97434782:GCG:G	donor_gain	1.0000
13:97434785:G:GG	donor_gain	1.0000
13:97434783:CGGT:C	donor_loss	0.9900
13:97434784:GGTGA:G	donor_loss	0.9900
13:97434786:T:A	donor_loss	0.9900
13:97434787:GAGC:G	donor_loss	0.9900
13:97464199:TCATA:T	acceptor_loss	0.9900
13:97464200:CATAG:C	acceptor_loss	0.9900
13:97464202:TAGG:T	acceptor_loss	0.9900
13:97464203:A:T	acceptor_loss	0.9900
13:97464204:G:GA	acceptor_loss	0.9900
13:97464204:GGTAT:G	acceptor_gain	0.9900
13:97439088:G:GT	donor_gain	0.9800
13:97439089:A:T	donor_gain	0.9800
13:97464203:A:AG	acceptor_gain	0.9800
13:97464204:G:GG	acceptor_gain	0.9800
13:97464204:GGT:G	acceptor_gain	0.9800
13:97434780:AAGCG:A	donor_gain	0.9700
13:97435556:ATT:A	donor_gain	0.9700
13:97464194:T:G	acceptor_gain	0.9700
13:97434744:G:GT	donor_gain	0.9600
13:97464193:A:AG	acceptor_gain	0.9600
13:97434781:AGCG:A	donor_gain	0.9500
13:97434782:GCGG:G	donor_gain	0.9500
13:97449740:T:G	acceptor_gain	0.9500
13:97464203:AG:A	acceptor_gain	0.9400
13:97464204:GG:G	acceptor_gain	0.9400
13:97434783:CG:C	donor_gain	0.9300
13:97434784:GG:G	donor_gain	0.9300
13:97464204:GGTA:G	acceptor_gain	0.9300

AlphaMissense

1210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:97434498:G:C	G10R	1.000
13:97434513:G:C	G15R	1.000
13:97434514:G:A	G15D	1.000
13:97434516:A:C	K16Q	1.000
13:97434517:A:T	K16I	1.000
13:97434518:A:C	K16N	1.000
13:97434518:A:T	K16N	1.000
13:97434520:C:T	S17F	1.000
13:97434526:T:C	L19P	1.000
13:97434552:T:C	F28L	1.000
13:97434554:C:A	F28L	1.000
13:97434554:C:G	F28L	1.000
13:97434628:T:C	L53P	1.000
13:97434637:T:C	L56P	1.000
13:97434639:G:A	D57N	1.000
13:97434639:G:C	D57H	1.000
13:97434639:G:T	D57Y	1.000
13:97434640:A:C	D57A	1.000
13:97434640:A:G	D57G	1.000
13:97434640:A:T	D57V	1.000
13:97434641:C:A	D57E	1.000
13:97434641:C:G	D57E	1.000
13:97434648:G:C	G60R	1.000
13:97434648:G:T	G60C	1.000
13:97434660:T:C	F64L	1.000
13:97434661:T:G	F64C	1.000
13:97434662:C:A	F64L	1.000
13:97434662:C:G	F64L	1.000
13:97434702:T:C	F78L	1.000
13:97434704:C:A	F78L	1.000

dbSNP variants (sampled 300 via entrez): RS1000035438 (13:97462775 G>A,C), RS1000144834 (13:97456332 C>T), RS1000201646 (13:97442445 A>G), RS1000222244 (13:97445937 G>A), RS1000222448 (13:97435168 A>G), RS1000286064 (13:97456701 G>A), RS1000315702 (13:97442749 T>C), RS1000346184 (13:97442345 A>G), RS1000349999 (13:97462062 ATATT>A), RS1000477216 (13:97435198 C>G), RS1000632234 (13:97437145 T>C), RS1000723610 (13:97467473 T>G), RS1000774932 (13:97467157 T>G), RS1000819837 (13:97435421 T>C), RS1000863869 (13:97442702 A>T)

Disease associations

OMIM: gene MIM:179540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003154_4	Peripheral artery disease	7.000000e-14
GCST003875_11	Gut microbiota (bacterial taxa)	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Endosulfan	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression, increases methylation	2
FR900359	decreases phosphorylation	1
testosterone enanthate	affects expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
mevalonolactone	increases farnesylation	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
N-(3-(aminomethyl)benzyl)acetamidine	decreases reaction, increases activity	1
K 7174	increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
Resveratrol	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Androgens	affects reaction, increases expression, affects response to substance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methotrexate	increases expression	1

Clinical trials (associated diseases)

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