RADIL

Summary

RADIL (Rap associating with DIL domain, HGNC:22226) is a protein-coding gene on chromosome 7p22.1, encoding Ras-associating and dilute domain-containing protein (Q96JH8). Downstream effector of Rap required for cell adhesion and migration of neural crest precursors during development.

Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex.

Source: NCBI Gene 55698 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 267 total
• MANE Select transcript: NM_018059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22226
Approved symbol	RADIL
Name	Rap associating with DIL domain
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10324, KIAA1849, RASIP2
Ensembl gene	ENSG00000157927
Ensembl biotype	protein_coding
OMIM	611491
Entrez	55698

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 retained_intron, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000399583, ENST00000445392, ENST00000457174, ENST00000469399, ENST00000472999, ENST00000473130, ENST00000484211, ENST00000904466

RefSeq mRNA: 1 — MANE Select: NM_018059 NM_018059

CCDS: CCDS43544

Canonical transcript exons

ENST00000399583 — 15 exons

Exon	Start	End
ENSE00001035917	4877605	4878203
ENSE00001539243	4834607	4835239
ENSE00001882774	4883596	4883716
ENSE00003487143	4799630	4799769
ENSE00003491664	4836358	4836605
ENSE00003494288	4800171	4800310
ENSE00003506406	4805566	4805716
ENSE00003517615	4817239	4817351
ENSE00003576306	4832141	4832178
ENSE00003585822	4801653	4801995
ENSE00003585824	4816228	4816465
ENSE00003607340	4797055	4799483
ENSE00003616012	4803546	4803754
ENSE00003661234	4815278	4815450
ENSE00003664222	4822394	4822554

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 98.02.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1465 / max 73.2341, expressed in 687 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82553	1.3505	581
82552	0.7729	388
82547	0.0231	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.02	gold quality
secondary oocyte	CL:0000655	97.18	gold quality
cerebellar vermis	UBERON:0004720	86.59	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.17	gold quality
cerebellar hemisphere	UBERON:0002245	84.61	gold quality
cerebellar cortex	UBERON:0002129	84.55	gold quality
cerebellum	UBERON:0002037	84.39	gold quality
right testis	UBERON:0004534	83.20	gold quality
left testis	UBERON:0004533	82.58	gold quality
pons	UBERON:0000988	81.89	silver quality
tibial nerve	UBERON:0001323	81.84	gold quality
sural nerve	UBERON:0015488	81.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	81.73	silver quality
apex of heart	UBERON:0002098	81.64	gold quality
hypothalamus	UBERON:0001898	81.14	gold quality
testis	UBERON:0000473	80.83	gold quality
substantia nigra pars compacta	UBERON:0001965	80.35	silver quality
epithelial cell of pancreas	CL:0000083	80.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.10	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.00	silver quality
lateral globus pallidus	UBERON:0002476	79.77	silver quality
upper arm skin	UBERON:0004263	79.75	gold quality
superior vestibular nucleus	UBERON:0007227	79.67	silver quality
trigeminal ganglion	UBERON:0001675	79.37	silver quality
ventricular zone	UBERON:0003053	79.33	gold quality
right lung	UBERON:0002167	79.25	gold quality
cardiac atrium	UBERON:0002081	79.20	gold quality
vena cava	UBERON:0004087	79.11	gold quality
right atrium auricular region	UBERON:0006631	79.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting RADIL, 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-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-4708-5P	97.77	67.82	831

Literature-anchored findings (GeneRIF, showing 4)

• Gbetagamma subunits enter in a protein complex with activated Rap1a and its effector Radil; this complex is required downstream of receptor stimulation for the activation of integrins and the positive modulation of cell-matrix adhesiveness. (PMID:20048162)
• Studies indicate that Radil regulates neutrophil adhesion and motility by linking Rap1 to beta2-integrin activation. +++ ERROR +++ studies establish that Radil regulates neutrophil adhesion and motility by linking Rap1 to beta2-integrin activation. (PMID:23097489)
• It was shown that KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. Radil is also important for breast cancer cell proliferation and metastasis. (PMID:23209302)
• Identification of Radil as a Ras binding partner and putative activator. (PMID:33482197)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	radil	ENSDARG00000079779
mus_musculus	Radil	ENSMUSG00000029576
rattus_norvegicus	Radil	ENSRNOG00000024456

Paralogs (1): RASIP1 (ENSG00000105538)

Protein

Protein identifiers

Ras-associating and dilute domain-containing protein — Q96JH8 (reviewed: Q96JH8)

All UniProt accessions (3): C9J7G0, Q96JH8, F8WEM1

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector of Rap required for cell adhesion and migration of neural crest precursors during development.

Subunit / interactions. Interacts with RAP1A; in a GTP-dependent manner. Does not interact with members of the Ras family. Interacts (via PDZ domain) with KIF14; is recruited to the microtubule network restricting its interaction with activated RAP1A.

Similarity. Belongs to the RADIL family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96JH8-4	4	yes
Q96JH8-2	2
Q96JH8-3	3
Q96JH8-1	1

RefSeq proteins (1): NP_060529* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000253	FHA_dom	Domain
IPR001478	PDZ	Domain
IPR002710	Dilute_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR037983	CBD_Rasip1/Radil	Domain
IPR052072	Vascular_dev_regulator	Family

Pfam: PF00498, PF00595, PF00788, PF01843

UniProt features (43 total): strand 10, helix 8, modified residue 6, domain 4, splice variant 4, sequence variant 4, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3EC8	X-RAY DIFFRACTION	2.6
1UM1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JH8-F1	69.47	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.

Post-translational modifications (6): 216, 219, 221, 393, 890, 206

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GCANCTGNY_MYOD_Q6, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, AATGGAG_MIR136, chr7p22, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_MESENCHYME_DEVELOPMENT, GOBP_STEM_CELL_DIFFERENTIATION, GOBP_CELL_SUBSTRATE_ADHESION, NIKOLSKY_BREAST_CANCER_7P22_AMPLICON, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (4): neural crest cell migration (GO:0001755), signal transduction (GO:0007165), substrate adhesion-dependent cell spreading (GO:0034446), cell adhesion (GO:0007155)

GO Molecular Function (2): GTPase binding (GO:0051020), protein binding (GO:0005515)

GO Cellular Component (2): microtubule (GO:0005874), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
neural crest cell development	1
mesenchymal cell migration	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell-substrate adhesion	1
enzyme binding	1
binding	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cellular_component	1

Protein interactions and networks

STRING

1927 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RADIL	CCDC187	A0A096LP49	563
RADIL	RASGEF1C	Q8N431	493
RADIL	RAP1A	P10113	456
RADIL	HRAS	P01112	440
RADIL	RRAD	P55042	433
RADIL	PITPNC1	Q9UKF7	395
RADIL	TMEM225	Q6GV28	380
RADIL	GGNBP2	Q9H3C7	380
RADIL	GIGYF2	Q6Y7W6	376
RADIL	AGGF1	Q8N302	367
RADIL	MYO5A	Q9Y4I1	366
RADIL	PRMT2	P55345	365
RADIL	NUTM1	Q86Y26	356
RADIL	RAVER1	Q8IY67	353
RADIL	CFAP65	Q6ZU64	348

IntAct

438 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
KRT31	RADIL	psi-mi:“MI:0915”(physical association)	0.720
RADIL	GATA1	psi-mi:“MI:0915”(physical association)	0.560
RADIL	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
RADIL	CEP76	psi-mi:“MI:0915”(physical association)	0.560
RADIL	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.560
GATA1	RADIL	psi-mi:“MI:0915”(physical association)	0.560
MRFAP1L1	RADIL	psi-mi:“MI:0915”(physical association)	0.560
CEP76	RADIL	psi-mi:“MI:0915”(physical association)	0.560
APOC1	RADIL	psi-mi:“MI:0915”(physical association)	0.560
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FLRT1	TCAF2	psi-mi:“MI:0914”(association)	0.530
RADIL	E6	psi-mi:“MI:0407”(direct interaction)	0.440
NRXN3	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
RADIL	PTEN	psi-mi:“MI:0407”(direct interaction)	0.440
MCM7	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
MMP24	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
WWTR1	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
TTC24	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (65): RADIL (Two-hybrid), RADIL (Two-hybrid), RADIL (Two-hybrid), CEP76 (Two-hybrid), MRFAP1L1 (Two-hybrid), RADIL (Affinity Capture-MS), RADIL (Affinity Capture-MS), RADIL (Two-hybrid), RHOXF2 (Two-hybrid), RADIL (Two-hybrid), RADIL (Affinity Capture-MS), RADIL (Affinity Capture-MS), RADIL (Affinity Capture-MS), RADIL (Affinity Capture-MS), RADIL (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: A0A140LI67, A5PKA5, A7UA95, E1JIT7, O14910, O15018, O19132, O35274, O35867, O35889, O62666, O62674, O62675, O62676, O62677, O62678, O88951, O88952, P11434, P29475, P29476, P31016, P51140, P55196, P57105, P78352, Q07436, Q0P5F3, Q12923, Q14005, Q29498, Q2KIB6, Q32LM6, Q3T0C9, Q3UHD6, Q4KL35, Q5F425, Q5RAA5, Q62108, Q64512

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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
Tight junction interactions	11	28.5×	5e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	28.4×	1e-05
Activation of BAD and translocation to mitochondria	5	26.8×	2e-04
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	23.6×	2e-04
Ephrin signaling	5	20.1×	5e-04
Activation of BH3-only proteins	5	17.5×	8e-04
RHO GTPases activate PKNs	6	13.4×	5e-04
FOXO-mediated transcription	5	11.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
calcium-independent cell-cell adhesion	10	44.3×	8e-12
bicellular tight junction assembly	11	20.1×	4e-09
ephrin receptor signaling pathway	8	15.2×	2e-05
maintenance of blood-brain barrier	5	13.3×	8e-03
cell-cell adhesion	10	5.6×	4e-03
cell adhesion	23	4.8×	3e-07
angiogenesis	12	4.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	233
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3401 predictions. Top by Δscore:

Variant	Effect	Δscore
7:4800166:CTCA:C	donor_loss	1.0000
7:4800167:TCA:T	donor_loss	1.0000
7:4800168:CACC:C	donor_loss	1.0000
7:4800169:A:AC	donor_gain	1.0000
7:4800169:ACCAT:A	donor_gain	1.0000
7:4800170:C:CC	donor_gain	1.0000
7:4800170:CCAT:C	donor_gain	1.0000
7:4800170:CCATC:C	donor_gain	1.0000
7:4803750:ATCCT:A	acceptor_gain	1.0000
7:4803751:TCCT:T	acceptor_gain	1.0000
7:4803752:CCTC:C	acceptor_gain	1.0000
7:4803753:CT:C	acceptor_gain	1.0000
7:4803755:C:CC	acceptor_gain	1.0000
7:4803755:CT:C	acceptor_loss	1.0000
7:4803756:T:A	acceptor_loss	1.0000
7:4815446:GGGGC:G	acceptor_gain	1.0000
7:4815447:GGGC:G	acceptor_gain	1.0000
7:4815448:GGC:G	acceptor_gain	1.0000
7:4815449:GC:G	acceptor_gain	1.0000
7:4815450:CC:C	acceptor_gain	1.0000
7:4815451:C:CC	acceptor_gain	1.0000
7:4815451:CTGT:C	acceptor_loss	1.0000
7:4815452:T:A	acceptor_loss	1.0000
7:4815453:G:C	acceptor_gain	1.0000
7:4816222:CCTCA:C	donor_loss	1.0000
7:4816223:CTCAC:C	donor_loss	1.0000
7:4816224:TCA:T	donor_loss	1.0000
7:4816225:CACC:C	donor_loss	1.0000
7:4816226:A:T	donor_loss	1.0000
7:4816226:ACC:A	donor_gain	1.0000

AlphaMissense

6912 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:4877898:A:T	V81D	0.999
7:4877903:C:A	K79N	0.999
7:4877903:C:G	K79N	0.999
7:4877936:A:C	F68L	0.999
7:4877936:A:T	F68L	0.999
7:4877938:A:G	F68L	0.999
7:4799675:A:G	I1026T	0.998
7:4834980:C:A	G348V	0.998
7:4834980:C:T	G348E	0.998
7:4834981:C:A	G348W	0.998
7:4835129:G:C	C298W	0.998
7:4835131:A:G	C298R	0.998
7:4835196:C:T	G276D	0.998
7:4836389:A:G	L251P	0.998
7:4877721:G:T	P140H	0.998
7:4877762:C:A	W126C	0.998
7:4877762:C:G	W126C	0.998
7:4877865:A:G	L92P	0.998
7:4877900:G:C	S80R	0.998
7:4877900:G:T	S80R	0.998
7:4877902:T:G	S80R	0.998
7:4877905:T:C	K79E	0.998
7:4877934:C:T	G69E	0.998
7:4877946:A:G	L65P	0.998
7:4799436:A:T	V1057D	0.997
7:4799442:A:G	F1055S	0.997
7:4799738:A:T	I1005N	0.997
7:4834981:C:G	G348R	0.997
7:4834981:C:T	G348R	0.997
7:4834998:C:A	G342V	0.997

dbSNP variants (sampled 300 via entrez): RS1000020499 (7:4819719 T>C), RS1000052134 (7:4874152 G>A), RS1000066065 (7:4879976 C>T), RS1000083275 (7:4837528 C>A,G), RS1000083496 (7:4880089 G>A), RS1000092283 (7:4819857 G>A), RS1000120521 (7:4848543 G>A,C), RS1000171671 (7:4805052 C>T), RS1000191450 (7:4864783 C>T), RS1000203557 (7:4843794 C>G), RS1000296583 (7:4837110 T>G), RS1000311427 (7:4811287 G>C), RS1000351672 (7:4850158 T>C), RS1000371842 (7:4871527 C>T), RS1000388775 (7:4839129 G>A)

Disease associations

OMIM: gene MIM:611491 | disease phenotypes: MIM:243310

GenCC curated gene-disease

Mondo (1): Baraitser-Winter syndrome 1 (MONDO:0009470)

Orphanet (2): Short stature-intellectual disability-eye anomalies-cleft lip/palate syndrome (Orphanet:2649), Baraitser-Winter cerebrofrontofacial syndrome (Orphanet:2995)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_23	Obesity-related traits	6.000000e-06
GCST010396_275	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-07
GCST010796_5292	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Valproic Acid	affects expression, increases expression, increases methylation	3
perfluoro-n-nonanoic acid	affects methylation, increases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
1-hydroxypyrene	decreases methylation, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	decreases methylation	1
Triclosan	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Metals, Heavy	affects cotreatment, decreases methylation	1

Clinical trials (associated diseases)

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