RAB3IL1

Summary

RAB3IL1 (RAB3A interacting protein like 1, HGNC:9780) is a protein-coding gene on chromosome 11q12.2-q12.3, encoding Guanine nucleotide exchange factor for Rab-3A (Q8TBN0). Guanine nucleotide exchange factor (GEF) which may activate RAB3A, a GTPase that regulates synaptic vesicle exocytosis.

This gene encodes a guanine nucleotide exchange factor for the ras-related protein Rab3A. The encoded protein binds Rab3a and the inositol hexakisphosphate kinase InsP6K1. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7.

Source: NCBI Gene 5866 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_013401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9780
Approved symbol	RAB3IL1
Name	RAB3A interacting protein like 1
Location	11q12.2-q12.3
Locus type	gene with protein product
Status	Approved
Aliases	GRAB
Ensembl gene	ENSG00000167994
Ensembl biotype	protein_coding
OMIM	621025
Entrez	5866

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000301773, ENST00000394836, ENST00000526200, ENST00000530888, ENST00000531922, ENST00000533136, ENST00000867933, ENST00000867934, ENST00000867935, ENST00000867936, ENST00000867937, ENST00000923689, ENST00000964391, ENST00000964392

RefSeq mRNA: 2 — MANE Select: NM_013401 NM_001271686, NM_013401

CCDS: CCDS60809, CCDS8014

Canonical transcript exons

ENST00000394836 — 10 exons

Exon	Start	End
ENSE00001119132	61907565	61907660
ENSE00001119133	61899314	61899380
ENSE00001119134	61904754	61904882
ENSE00001119135	61907393	61907470
ENSE00001119136	61904546	61904658
ENSE00001119139	61902442	61902541
ENSE00001119140	61906466	61906684
ENSE00001327994	61917357	61917566
ENSE00001335610	61908054	61908306
ENSE00002178705	61897301	61898360

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 93.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8928 / max 85.5147, expressed in 1299 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120056	4.3923	1257
120058	0.3258	72
120053	0.0623	18
120055	0.0586	18
120054	0.0538	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	93.01	silver quality
tibial nerve	UBERON:0001323	92.10	gold quality
left testis	UBERON:0004533	92.07	gold quality
right testis	UBERON:0004534	92.04	gold quality
right ovary	UBERON:0002118	91.97	gold quality
endocervix	UBERON:0000458	91.92	gold quality
apex of heart	UBERON:0002098	91.24	gold quality
body of uterus	UBERON:0009853	91.13	gold quality
left ovary	UBERON:0002119	90.85	gold quality
mucosa of stomach	UBERON:0001199	90.44	gold quality
olfactory bulb	UBERON:0002264	90.34	silver quality
testis	UBERON:0000473	89.53	gold quality
omental fat pad	UBERON:0010414	89.14	gold quality
peritoneum	UBERON:0002358	89.10	gold quality
left uterine tube	UBERON:0001303	88.83	gold quality
sural nerve	UBERON:0015488	88.26	gold quality
spleen	UBERON:0002106	88.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.00	gold quality
ectocervix	UBERON:0012249	86.91	gold quality
ovary	UBERON:0000992	86.52	gold quality
right atrium auricular region	UBERON:0006631	86.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.01	silver quality
subcutaneous adipose tissue	UBERON:0002190	85.71	gold quality
cardiac atrium	UBERON:0002081	85.41	gold quality
tongue squamous epithelium	UBERON:0006919	85.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.99	gold quality
left coronary artery	UBERON:0001626	84.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.82	gold quality
lower esophagus	UBERON:0013473	84.73	gold quality
coronary artery	UBERON:0001621	84.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting RAB3IL1, 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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-7155-5P	98.65	66.14	1290

Literature-anchored findings (GeneRIF, showing 3)

• Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB. (PMID:24072714)
• Rab27/Rabphilin3a/GRAB/Rab3 constitutes a signaling module in sperm exocytosis. (PMID:30599141)
• Identification of hub genes in unstable atherosclerotic plaque by conjoint analysis of bioinformatics. (PMID:33011223)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab3il1	ENSDARG00000007711
mus_musculus	Rab3il1	ENSMUSG00000024663
rattus_norvegicus	Rab3il1	ENSRNOG00000020349
caenorhabditis_elegans		WBGENE00010045

Paralogs (1): RAB3IP (ENSG00000127328)

Protein

Protein identifiers

Guanine nucleotide exchange factor for Rab-3A — Q8TBN0 (reviewed: Q8TBN0)

Alternative names: Rab-3A-interacting-like protein 1, Rabin3-like 1

All UniProt accessions (3): E9PK89, Q8TBN0, H0YD19

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) which may activate RAB3A, a GTPase that regulates synaptic vesicle exocytosis. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May also activate RAB8A and RAB8B.

Subunit / interactions. Interacts with RAB3A and IHPK1 through the coiled-coil domain. This interaction is competitive. IHPK1 kinase activity is not required for this interaction.

Similarity. Belongs to the SEC2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBN0-1	1	yes
Q8TBN0-2	2

RefSeq proteins (2): NP_001258615, NP_037533* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009449	Sec2_N	Domain
IPR040351	RAB3IL/RAB3IP/Sec2	Family

Pfam: PF06428, PF25555

UniProt features (14 total): compositionally biased region 3, region of interest 2, splice variant 2, sequence variant 2, modified residue 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4LI0	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBN0-F1	79.83	0.60

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 (2): 168, 179

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: 142 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, REACTOME_MEMBRANE_TRAFFICKING, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, MYCMAX_01, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, USF_01, USF_02, BURTON_ADIPOGENESIS_10, SHEN_SMARCA2_TARGETS_DN, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, USF2_Q6, MYC_Q2, MYCMAX_03, MAX_01, ARNT_01

GO Biological Process (1): protein transport (GO:0015031)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

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	1
intracellular protein localization	1
establishment of protein localization	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB3IL1	A2M	P01023	949
RAB3IL1	IP6K1	Q92551	801
RAB3IL1	RAB3A	P20336	698
RAB3IL1	RAB11A	P24410	686
RAB3IL1	RAB8A	P24407	643
RAB3IL1	RABGEF1	Q9UJ41	606
RAB3IL1	ARF1	P10947	598
RAB3IL1	RAB8B	Q92930	586
RAB3IL1	TRIP11	Q15643	570
RAB3IL1	RPH3A	Q9Y2J0	517
RAB3IL1	RAB40AL	P0C0E4	516
RAB3IL1	CASP3	P42574	509
RAB3IL1	ANKRD27	Q96NW4	508
RAB3IL1	RAB32	Q13637	501
RAB3IL1	RAB21	Q9UL25	498

IntAct

111 interactions, top by confidence:

A	B	Type	Score
RAB3IL1	RAB3IP	psi-mi:“MI:0915”(physical association)	0.890
RAB3IP	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.890
RAB3IP	TRAPPC3	psi-mi:“MI:0914”(association)	0.700
NOTCH2NLA	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.670
RAB3IL1	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.670
RAB3IL1	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
RAB3IL1	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.670
RAB3IL1	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
RAB3IL1	TIGD7	psi-mi:“MI:0915”(physical association)	0.560
RAB3IL1	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
KRT40	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
SATB2	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
TIGD7	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
RAB3IL1	CCDC57	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): RAB3IL1 (Two-hybrid), RAB3IL1 (Two-hybrid), MTUS2 (Two-hybrid), SATB2 (Two-hybrid), TIGD7 (Two-hybrid), RAB3IP (Two-hybrid), KRT40 (Two-hybrid), CCDC57 (Two-hybrid), NOTCH2NL (Two-hybrid), RAB3IL1 (Biochemical Activity), RAB3IP (Affinity Capture-MS), TMEM102 (Affinity Capture-MS), PPFIA3 (Affinity Capture-MS), ATG4C (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: O13930, Q2KJ58, Q4WWM8, Q5AL49, Q8TBN0, Q62739, Q68EF0, Q8VDV3, Q96QF0, Q99NH3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“Elongator complex”	“up-regulates activity”	RAB3IL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
RAB GEFs exchange GTP for GDP on RABs	8	34.2×	7e-09
COPII-mediated vesicle transport	6	33.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	6	156.5×	1e-10
endoplasmic reticulum to Golgi vesicle-mediated transport	6	21.5×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1886 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61899273:C:CA	donor_gain	1.0000
11:61899312:ACCGT:A	donor_gain	1.0000
11:61899313:CCGTC:C	donor_gain	1.0000
11:61902436:ACTC:A	donor_loss	1.0000
11:61902437:CTCA:C	donor_loss	1.0000
11:61902438:TCA:T	donor_loss	1.0000
11:61902439:CACCC:C	donor_loss	1.0000
11:61902440:A:AC	donor_gain	1.0000
11:61902440:AC:A	donor_gain	1.0000
11:61902441:C:CC	donor_gain	1.0000
11:61902441:C:CG	donor_loss	1.0000
11:61902441:CC:C	donor_gain	1.0000
11:61902537:ATGTG:A	acceptor_gain	1.0000
11:61902538:TGTG:T	acceptor_gain	1.0000
11:61902539:GTG:G	acceptor_gain	1.0000
11:61902540:TG:T	acceptor_gain	1.0000
11:61902542:C:CC	acceptor_gain	1.0000
11:61904540:G:C	donor_gain	1.0000
11:61904541:CTTA:C	donor_loss	1.0000
11:61904542:TTA:T	donor_loss	1.0000
11:61904543:TACT:T	donor_loss	1.0000
11:61904544:A:AC	donor_gain	1.0000
11:61904544:A:C	donor_loss	1.0000
11:61904545:C:CC	donor_gain	1.0000
11:61904545:CTTG:C	donor_gain	1.0000
11:61904656:GAG:G	acceptor_gain	1.0000
11:61904656:GAGC:G	acceptor_loss	1.0000
11:61904657:AGCT:A	acceptor_loss	1.0000
11:61904658:GC:G	acceptor_loss	1.0000
11:61904659:C:CC	acceptor_gain	1.0000

AlphaMissense

2470 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61907446:C:G	A129P	0.999
11:61907568:A:C	F119L	0.999
11:61907568:A:T	F119L	0.999
11:61907570:A:G	F119L	0.999
11:61907584:A:G	L114P	0.999
11:61906653:A:G	L157S	0.998
11:61906669:C:G	A152P	0.998
11:61907569:A:C	F119C	0.998
11:61907593:A:G	L111P	0.998
11:61906674:A:G	L150P	0.997
11:61907404:C:G	A143P	0.997
11:61906644:A:G	L160P	0.996
11:61906656:G:T	A156D	0.996
11:61906657:C:G	A156P	0.996
11:61907614:C:G	R104P	0.996
11:61898327:C:G	R367P	0.995
11:61902449:C:G	R331P	0.995
11:61902464:A:T	I326N	0.995
11:61904849:A:G	W231R	0.995
11:61904849:A:T	W231R	0.995
11:61906641:A:T	V161D	0.995
11:61906649:C:A	K158N	0.995
11:61906649:C:G	K158N	0.995
11:61907570:A:T	F119I	0.995
11:61907572:A:G	L118P	0.995
11:61907579:C:G	A116P	0.995
11:61907605:A:G	L107P	0.995
11:61899346:C:G	R345P	0.994
11:61904618:A:T	L276H	0.994
11:61907412:A:G	L140P	0.994

dbSNP variants (sampled 300 via entrez): RS1000057770 (11:61929174 C>T), RS1000113162 (11:61906514 C>A,T), RS1000253539 (11:61936602 A>G), RS1000266218 (11:61918321 T>C), RS1000284636 (11:61936884 A>G), RS1000327429 (11:61901267 A>C), RS1000446613 (11:61905242 C>T), RS1000507372 (11:61930198 G>A), RS1000637785 (11:61906281 C>G), RS1000870236 (11:61919693 T>C), RS1000882851 (11:61925350 G>C), RS1000893539 (11:61901049 A>C), RS1000896941 (11:61919472 C>G,T), RS1000913882 (11:61924976 G>A), RS1000924446 (11:61907153 A>C)

Disease associations

OMIM: gene MIM:621025 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001178_15	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	2.000000e-17
GCST001179_20	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	3.000000e-35
GCST001180_6	Plasma omega-3 polyunsaturated fatty acid levels (alphalinolenic acid)	1.000000e-12
GCST001834_5	Oleic acid (18:1n-9) levels	2.000000e-32
GCST002444_5	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5.000000e-168
GCST002448_6	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	4.000000e-140
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7.000000e-147
GCST002450_8	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-72
GCST002712_2	Red blood cell fatty acid levels	8.000000e-90
GCST002712_4	Red blood cell fatty acid levels	3.000000e-305
GCST002712_9	Red blood cell fatty acid levels	6.000000e-43
GCST009391_2118	Metabolite levels	4.000000e-11
GCST009391_407	Metabolite levels	9.000000e-13
GCST90002406_370	Reticulocyte fraction of red cells	9.000000e-12
GCST90011899_120	Aspartate aminotransferase levels	2.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007760	eicosapentaenoic acid measurement
EFO:0006809	docosapentaenoic acid measurement
EFO:0007759	alpha-linolenic acid measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006808	arachidonic acid measurement
EFO:0006811	linolenic acid measurement
EFO:0006807	linoleic acid measurement
EFO:0010382	phosphatidylcholine 36:4 measurement
EFO:0010387	phosphatidylcholine 38:5 measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects expression, decreases expression	2
FR900359	decreases phosphorylation	1
methyleugenol	increases expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
boron nitride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1

Clinical trials (associated diseases)

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