RINL

Summary

RINL (Ras and Rab interactor like, HGNC:24795) is a protein-coding gene on chromosome 19q13.2, encoding Ras and Rab interactor-like protein (Q6ZS11). Guanine nucleotide exchange factor (GEF) for RAB5A and RAB22A that activates RAB5A and RAB22A by exchanging bound GDP for free GTP.

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in endocytosis. Predicted to be located in ruffle. Predicted to be active in cytosol and endocytic vesicle.

Source: NCBI Gene 126432 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001195833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24795
Approved symbol	RINL
Name	Ras and Rab interactor like
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45909
Ensembl gene	ENSG00000187994
Ensembl biotype	protein_coding
OMIM	620678
Entrez	126432

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 retained_intron, 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000589111, ENST00000591812, ENST00000593424, ENST00000593809, ENST00000596919, ENST00000596961, ENST00000598048, ENST00000598904, ENST00000599911, ENST00000602238

RefSeq mRNA: 2 — MANE Select: NM_001195833 NM_001195833, NM_198445

CCDS: CCDS12522, CCDS59386

Canonical transcript exons

ENST00000591812 — 12 exons

Exon	Start	End
ENSE00001369587	38871078	38871227
ENSE00001380807	38871647	38871711
ENSE00002932907	38878232	38878275
ENSE00003468059	38869573	38869704
ENSE00003533848	38876331	38876490
ENSE00003555105	38869943	38870260
ENSE00003582635	38869247	38869410
ENSE00003602429	38870570	38870992
ENSE00003628282	38873886	38873988
ENSE00003638910	38876693	38876781
ENSE00003658347	38871798	38871870
ENSE00003850187	38867830	38869166

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 89.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5578 / max 63.0314, expressed in 1360 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180822	2.5109	576
180821	2.0470	1030

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	89.93	gold quality
blood	UBERON:0000178	89.01	gold quality
lymph node	UBERON:0000029	88.24	gold quality
vermiform appendix	UBERON:0001154	83.98	gold quality
spleen	UBERON:0002106	82.95	gold quality
bone marrow cell	CL:0002092	82.12	gold quality
tonsil	UBERON:0002372	81.98	gold quality
islet of Langerhans	UBERON:0000006	81.89	gold quality
pancreas	UBERON:0001264	81.40	gold quality
body of pancreas	UBERON:0001150	81.31	gold quality
leukocyte	CL:0000738	80.97	gold quality
monocyte	CL:0000576	80.24	gold quality
bone marrow	UBERON:0002371	79.77	gold quality
nucleus accumbens	UBERON:0001882	77.17	gold quality
prefrontal cortex	UBERON:0000451	77.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.95	gold quality
putamen	UBERON:0001874	75.86	gold quality
cortex of kidney	UBERON:0001225	75.83	gold quality
caudate nucleus	UBERON:0001873	75.25	gold quality
adult mammalian kidney	UBERON:0000082	75.08	gold quality
esophagus mucosa	UBERON:0002469	75.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.99	gold quality
anterior cingulate cortex	UBERON:0009835	74.91	gold quality
frontal cortex	UBERON:0001870	74.81	gold quality
duodenum	UBERON:0002114	74.68	gold quality
small intestine	UBERON:0002108	74.66	gold quality
gall bladder	UBERON:0002110	74.24	gold quality
placenta	UBERON:0001987	74.11	gold quality
right lobe of liver	UBERON:0001114	74.04	gold quality
liver	UBERON:0002107	74.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	22.69
E-ANND-3	no	1.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting RINL, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6840-3P	98.68	65.95	1923

Literature-anchored findings (GeneRIF, showing 1)

• RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin. (PMID:22291991)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rinl	ENSMUSG00000051735
rattus_norvegicus	Rinl	ENSRNOG00000025354
drosophila_melanogaster	spri	FBGN0085443
drosophila_melanogaster	Rabex-5	FBGN0262937
caenorhabditis_elegans		WBGENE00008183
caenorhabditis_elegans		WBGENE00012644

Paralogs (6): VPS9D1 (ENSG00000075399), RIN3 (ENSG00000100599), RIN2 (ENSG00000132669), RABGEF1 (ENSG00000154710), GAPVD1 (ENSG00000165219), RIN1 (ENSG00000174791)

Protein

Protein identifiers

Ras and Rab interactor-like protein — Q6ZS11 (reviewed: Q6ZS11)

All UniProt accessions (3): Q6ZS11, M0QY08, M0QZ15

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) for RAB5A and RAB22A that activates RAB5A and RAB22A by exchanging bound GDP for free GTP. Plays a role in endocytosis via its role in activating Rab family members.

Subunit / interactions. Interacts with RAB5A, RAB22A and MUSK.

Subcellular location. Cell projection. Ruffle. Cytoplasmic vesicle.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZS11-1	1	yes
Q6ZS11-2	2

RefSeq proteins (2): NP_001182762, NP_940847 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003123	VPS9	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037191	VPS9_dom_sf	Homologous_superfamily
IPR045046	Vps9-like	Family

Pfam: PF02204

UniProt features (10 total): region of interest 3, compositionally biased region 3, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZS11-F1	66.63	0.26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 114 (showing top): GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, DARWICHE_PAPILLOMA_PROGRESSION_RISK, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, PU1_Q6, RYTTCCTG_ETS2_B, RGAGGAARY_PU1_Q6, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, GOCC_ENDOCYTIC_VESICLE, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, MGGAAGTG_GABP_B, GOCC_CELL_LEADING_EDGE, ETS_Q4

GO Biological Process (3): endocytosis (GO:0006897), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267)

GO Cellular Component (6): ruffle (GO:0001726), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), endocytic vesicle (GO:0030139), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
GTPase regulator activity	2
cytoplasm	2
cellular anatomical structure	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
cytoskeleton	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RINL	RAB5A	P20339	691
RINL	RABGEF1	Q9UJ41	533
RINL	EPHA8	P29322	525
RINL	ANKS1A	Q92625	487
RINL	CCER2	I3L3R5	487
RINL	RAB21	Q9UL25	478
RINL	RAB31	Q13636	411
RINL	DYNLT4	Q5JR98	400
RINL	ARHGEF35	A5YM69	400
RINL	ALS2CL	Q60I27	398
RINL	RAB22A	Q9UL26	383
RINL	SPATA9	Q9BWV2	373
RINL	ANKRD27	Q96NW4	366
RINL	ALDH18A1	P54886	336
RINL	ANKRD46	Q86W74	335

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ANKRA2	RINL	psi-mi:“MI:0407”(direct interaction)	0.440
RIN3		psi-mi:“MI:0914”(association)	0.350
RINL	SERPINB8	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
FGFR1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
AATK	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
RET	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (13): RINL (Proximity Label-MS), RINL (Affinity Capture-MS), NTHL1 (Affinity Capture-MS), RIPPLY3 (Affinity Capture-MS), SUGP1 (Affinity Capture-MS), MICAL1 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), RINL (Affinity Capture-MS), RINL (Affinity Capture-MS), RINL (Affinity Capture-RNA), RINL (Proximity Label-MS), RINL (Proximity Label-MS), RINL (Proximity Label-MS)

ESM2 similar proteins: A6NE52, A9JTS5, D2HS90, D4A929, E1BD59, O15037, P33076, P58660, P79621, P97680, Q0P5G1, Q13671, Q16584, Q1JPD6, Q1LZD1, Q1W1Y5, Q2LGB3, Q3MHT4, Q3UPH7, Q3UPR7, Q53GL7, Q562E7, Q56B11, Q58EX7, Q5ND34, Q5XIS1, Q6ZS11, Q6ZS72, Q80UW5, Q80XI6, Q8BTN6, Q8CIE4, Q8IV53, Q8IZL8, Q8K330, Q8N9M5, Q8R3F9, Q8R5G7, Q8TE77, Q8TER5

Diamond homologs: A2RV61, A5D794, P59729, P97680, Q10NQ3, Q13671, Q14C86, Q6PAR5, Q6ZS11, Q80UW3, Q8TB24, Q8WYP3, Q921Q7, Q9D684, Q9LT31, O18973, Q8MQW8, Q9JM13, Q9UJ41, O74396, P54787

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

978 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38869406:CCCAG:C	acceptor_gain	1.0000
19:38869407:CCAGC:C	acceptor_gain	1.0000
19:38869490:C:A	donor_gain	1.0000
19:38869493:T:A	donor_gain	1.0000
19:38869571:AC:A	donor_gain	1.0000
19:38869572:CC:C	donor_gain	1.0000
19:38869572:CCCT:C	donor_gain	1.0000
19:38869590:T:C	donor_gain	1.0000
19:38869623:T:TA	donor_gain	1.0000
19:38869700:GGGAT:G	acceptor_gain	1.0000
19:38869701:GGAT:G	acceptor_gain	1.0000
19:38869702:GAT:G	acceptor_gain	1.0000
19:38869702:GATCT:G	acceptor_loss	1.0000
19:38869703:ATC:A	acceptor_loss	1.0000
19:38869704:TCT:T	acceptor_loss	1.0000
19:38869705:C:CA	acceptor_loss	1.0000
19:38869705:C:CC	acceptor_gain	1.0000
19:38869938:CTTA:C	donor_loss	1.0000
19:38869940:TACC:T	donor_loss	1.0000
19:38869942:C:CG	donor_loss	1.0000
19:38870610:T:TA	donor_gain	1.0000
19:38873885:CCT:C	donor_gain	1.0000
19:38873987:CT:C	acceptor_gain	1.0000
19:38869407:CCAG:C	acceptor_gain	0.9900
19:38869408:CAG:C	acceptor_gain	0.9900
19:38869408:CAGC:C	acceptor_gain	0.9900
19:38869410:GCTGG:G	acceptor_loss	0.9900
19:38869411:C:CC	acceptor_gain	0.9900
19:38869412:T:G	acceptor_loss	0.9900
19:38869481:G:A	donor_gain	0.9900

AlphaMissense

3617 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38869385:A:C	F500L	0.993
19:38869385:A:T	F500L	0.993
19:38869387:A:G	F500L	0.993
19:38869683:A:G	F455S	0.993
19:38869292:C:A	W531C	0.992
19:38869292:C:G	W531C	0.992
19:38869682:G:C	F455L	0.992
19:38869682:G:T	F455L	0.992
19:38869684:A:G	F455L	0.992
19:38873983:G:C	F72L	0.992
19:38873983:G:T	F72L	0.992
19:38873985:A:G	F72L	0.992
19:38869390:A:G	W499R	0.990
19:38869390:A:T	W499R	0.990
19:38869659:A:G	L463P	0.990
19:38869294:A:G	W531R	0.989
19:38869294:A:T	W531R	0.989
19:38869613:A:C	F478L	0.988
19:38869613:A:T	F478L	0.988
19:38869615:A:G	F478L	0.988
19:38870656:A:G	L313P	0.988
19:38871812:A:C	F124L	0.988
19:38871812:A:T	F124L	0.988
19:38871814:A:G	F124L	0.988
19:38869659:A:T	L463H	0.987
19:38870007:C:A	K426N	0.987
19:38870007:C:G	K426N	0.987
19:38869607:C:A	M480I	0.986
19:38869607:C:G	M480I	0.986
19:38869607:C:T	M480I	0.986

dbSNP variants (sampled 300 via entrez): RS1000582023 (19:38879506 G>A), RS1000713651 (19:38871337 G>GCTTA), RS1000744889 (19:38871092 T>A), RS1000968532 (19:38875170 A>G,T), RS1000999891 (19:38874987 T>C), RS1001308810 (19:38868624 C>G,T), RS1001310176 (19:38876628 A>G), RS1001413 (19:38876471 T>C,G), RS1001414 (19:38876174 C>T), RS1002010226 (19:38872116 C>T), RS1002982308 (19:38878078 G>A,T), RS1003169920 (19:38873338 A>G), RS1003412945 (19:38874900 C>A,T), RS1003695373 (19:38872903 A>G), RS1004487430 (19:38877414 G>A)

Disease associations

OMIM: gene MIM:620678 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Valproic Acid	increases expression, increases methylation, affects cotreatment	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydralazine	increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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