RGL1

Summary

RGL1 (ral guanine nucleotide dissociation stimulator like 1, HGNC:30281) is a protein-coding gene on chromosome 1q25.3, encoding Ral guanine nucleotide dissociation stimulator-like 1 (Q9NZL6). Probable guanine nucleotide exchange factor.

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction. Predicted to be located in cytosol. Predicted to be active in plasma membrane.

Source: NCBI Gene 23179 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_001297671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30281
Approved symbol	RGL1
Name	ral guanine nucleotide dissociation stimulator like 1
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	RGL
Ensembl gene	ENSG00000143344
Ensembl biotype	protein_coding
OMIM	605667
Entrez	23179

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000304685, ENST00000360851, ENST00000888232, ENST00000888233, ENST00000888234, ENST00000888235, ENST00000888236, ENST00000888237, ENST00000966019

RefSeq mRNA: 5 — MANE Select: NM_001297671 NM_001297669, NM_001297670, NM_001297671, NM_001297672, NM_015149

CCDS: CCDS1359, CCDS72992

Canonical transcript exons

ENST00000360851 — 18 exons

Exon	Start	End
ENSE00000959451	183912082	183912268
ENSE00000959452	183916447	183916701
ENSE00000959453	183922222	183922336
ENSE00001030129	183884723	183884938
ENSE00001030134	183892077	183892161
ENSE00001030135	183888474	183888577
ENSE00001030140	183907012	183907101
ENSE00001030144	183904850	183904971
ENSE00001030147	183880616	183880800
ENSE00001030152	183883786	183883910
ENSE00001030157	183902568	183902600
ENSE00001030159	183897808	183897897
ENSE00001030161	183865996	183866073
ENSE00001030164	183900150	183900236
ENSE00001030167	183847566	183847774
ENSE00001228975	183806375	183806485
ENSE00001431483	183805120	183805324
ENSE00003904023	183926105	183928532

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2501 / max 599.5676, expressed in 1529 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7169	16.2165	1333
7171	2.7928	819
7166	2.2195	856
7170	0.5186	268
7172	0.4867	167
7165	0.4695	171
7167	0.1994	100
7168	0.1383	46
7176	0.1004	29
7173	0.0567	16

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	98.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.47	gold quality
dorsal root ganglion	UBERON:0000044	97.42	gold quality
parietal pleura	UBERON:0002400	97.29	gold quality
germinal epithelium of ovary	UBERON:0001304	96.93	gold quality
trigeminal ganglion	UBERON:0001675	96.78	gold quality
pleura	UBERON:0000977	96.77	gold quality
middle temporal gyrus	UBERON:0002771	96.42	gold quality
visceral pleura	UBERON:0002401	96.18	gold quality
medial globus pallidus	UBERON:0002477	95.80	gold quality
entorhinal cortex	UBERON:0002728	95.59	gold quality
tendon of biceps brachii	UBERON:0008188	95.56	gold quality
pericardium	UBERON:0002407	95.43	gold quality
globus pallidus	UBERON:0001875	95.23	gold quality
renal glomerulus	UBERON:0000074	94.80	gold quality
metanephric glomerulus	UBERON:0004736	94.79	gold quality
cranial nerve II	UBERON:0000941	94.70	gold quality
tibia	UBERON:0000979	94.55	gold quality
postcentral gyrus	UBERON:0002581	94.52	gold quality
parietal lobe	UBERON:0001872	94.39	gold quality
decidua	UBERON:0002450	94.25	gold quality
periodontal ligament	UBERON:0008266	94.11	gold quality
corpus callosum	UBERON:0002336	93.87	gold quality
superior frontal gyrus	UBERON:0002661	93.87	gold quality
kidney epithelium	UBERON:0004819	93.86	gold quality
synovial joint	UBERON:0002217	93.82	gold quality
nephron tubule	UBERON:0001231	93.69	gold quality
inferior vagus X ganglion	UBERON:0005363	93.18	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.81	gold quality
lateral globus pallidus	UBERON:0002476	92.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	11.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting RGL1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6768-5P	99.92	67.36	1942

Literature-anchored findings (GeneRIF, showing 1)

• Structures of RGL1 RAS-Association Domain in Complex with KRAS and the Oncogenic G12V Mutant. (PMID:35257782)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgl1	ENSDARG00000005989
mus_musculus	Rgl1	ENSMUSG00000026482
rattus_norvegicus	Ralgdsl1	ENSRNOG00000002347

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RASGEF1C (ENSG00000146090), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ral guanine nucleotide dissociation stimulator-like 1 — Q9NZL6 (reviewed: Q9NZL6)

All UniProt accessions (1): Q9NZL6

UniProt curated annotations — full annotation on UniProt →

Function. Probable guanine nucleotide exchange factor.

Subunit / interactions. Interacts with Ras.

Tissue specificity. Expressed in a wide variety of tissues with strong expression being seen in the heart, brain, kidney, spleen and testis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZL6-1	A	yes
Q9NZL6-2	B

RefSeq proteins (5): NP_001284598, NP_001284599, NP_001284600, NP_001284601, NP_055964 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR030748	RGL1_RA	Domain
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily

Pfam: PF00617, PF00618, PF00788

UniProt features (24 total): strand 6, domain 3, sequence conflict 3, helix 3, compositionally biased region 3, sequence variant 2, chain 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7SCX	X-RAY DIFFRACTION	1.96
7SCW	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZL6-F1	71.94	0.43

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 (1): 520

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 347 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, WIELAND_UP_BY_HBV_INFECTION, EFC_Q6, NFKB_Q6, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, NFKB_C, FOSTER_TOLERANT_MACROPHAGE_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, USF_01, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION

GO Biological Process (3): small GTPase-mediated signal transduction (GO:0007264), Ras protein signal transduction (GO:0007265), signal transduction (GO:0007165)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular signaling cassette	1
small GTPase-mediated signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGL1	RALA	P11233	853
RGL1	LRPAP1	P30533	494
RGL1	RAP2A	P10114	491
RGL1	RGL2	O15211	478
RGL1	RALB	P11234	476
RGL1	RGL3	Q3MIN7	436
RGL1	RALGAPB	Q86X10	372
RGL1	PPP1R3A	Q16821	370
RGL1	SPINT3	P49223	358
RGL1	TIPE2	Q6P589	329
RGL1	RNF34	Q969K3	329
RGL1	SIK2	Q9H0K1	316
RGL1	A0A087WZY1	A0A087WZY1	307
RGL1	PENK	P01210	306
RGL1	PRH1	P02810	300

IntAct

7 interactions, top by confidence:

A	B	Type	Score
HRAS	RGL1	psi-mi:“MI:0407”(direct interaction)	0.740
RIT1	RGL1	psi-mi:“MI:0915”(physical association)	0.400
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
RGL1	TULP3	psi-mi:“MI:0914”(association)	0.350
RGL1	HRAS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): RGL1 (Affinity Capture-MS), RGL1 (Affinity Capture-RNA), RGL1 (Two-hybrid), RAP1A (Affinity Capture-MS), RAP1B (Affinity Capture-MS), TULP3 (Affinity Capture-MS), RAP2A (Affinity Capture-MS), RRAS2 (Affinity Capture-MS), ATL3 (Affinity Capture-MS), NRAS (Affinity Capture-MS), LENG8 (Affinity Capture-MS), HRAS (Affinity Capture-MS), ATL2 (Affinity Capture-MS), RGL1 (Protein-RNA), RGL1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5PK26, A6N9I4, F1LYQ8, F1M386, F1MSG6, F1PBJ0, F8VPU2, O00329, O15068, O35904, O94887, O95398, P0C643, Q0VGW0, Q15027, Q32N25, Q3TBD2, Q3U5C8, Q4R623, Q5R9B2, Q5RAB8, Q5RB40, Q5ZLD2, Q60695, Q61210, Q63406, Q64096, Q66K14, Q68DX3, Q68EF8, Q6DCK3, Q6P112, Q7LDG7, Q8BH88, Q8CHG7, Q8IV61, Q8K2H4, Q8TEU7, Q8VCC8, Q8WUY9

Diamond homologs: A2AR50, A2CEA7, B0M0P8, B0UXH6, F1M386, F1MSG6, F1PBJ0, O14827, P27671, P28818, P70392, Q03385, Q03386, Q07889, Q07890, Q12967, Q13905, Q13972, Q3MIN7, Q3UYI5, Q4R7W3, Q54FF3, Q54PQ4, Q54TK8, Q552M5, Q55GH9, Q5JS13, Q5ZJK0, Q60695, Q86G47, Q86X27, Q8CHG7, Q8IS14, Q8IS15, Q8IS16, Q8IS18, Q8IS20, Q8IS21, Q8SSQ0, Q8SSW7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5682 predictions. Top by Δscore:

Variant	Effect	Δscore
1:183739903:GTAGA:G	donor_gain	1.0000
1:183742125:GATCC:G	acceptor_gain	1.0000
1:183742286:GGAG:G	donor_gain	1.0000
1:183742287:GAGG:G	donor_gain	1.0000
1:183780986:G:GG	donor_gain	1.0000
1:183855747:G:GG	donor_gain	1.0000
1:183865986:A:AG	acceptor_gain	1.0000
1:183865987:T:G	acceptor_gain	1.0000
1:183865991:TACA:T	acceptor_loss	1.0000
1:183865993:CAGGT:C	acceptor_loss	1.0000
1:183865994:A:AT	acceptor_loss	1.0000
1:183865994:AG:A	acceptor_gain	1.0000
1:183865995:G:GA	acceptor_gain	1.0000
1:183865995:GG:G	acceptor_gain	1.0000
1:183865995:GGT:G	acceptor_gain	1.0000
1:183865995:GGTAT:G	acceptor_gain	1.0000
1:183866069:AGGAA:A	donor_gain	1.0000
1:183866070:GGAA:G	donor_gain	1.0000
1:183866070:GGAAG:G	donor_gain	1.0000
1:183866071:G:T	donor_gain	1.0000
1:183866071:GAA:G	donor_gain	1.0000
1:183866071:GAAG:G	donor_gain	1.0000
1:183866072:AA:A	donor_gain	1.0000
1:183866072:AAG:A	donor_loss	1.0000
1:183866074:G:GG	donor_gain	1.0000
1:183883908:GCA:G	donor_gain	1.0000
1:183883911:G:GG	donor_gain	1.0000
1:183884939:G:GG	donor_gain	1.0000
1:183888574:CAAGG:C	donor_loss	1.0000
1:183888575:AAGG:A	donor_loss	1.0000

AlphaMissense

5089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:183880641:T:A	W151R	1.000
1:183880641:T:C	W151R	1.000
1:183884834:T:C	F283L	1.000
1:183884836:T:A	F283L	1.000
1:183884836:T:G	F283L	1.000
1:183884921:T:A	W312R	1.000
1:183884921:T:C	W312R	1.000
1:183900190:T:C	L424P	1.000
1:183847638:G:C	A71P	0.999
1:183847641:G:C	G72R	0.999
1:183847642:G:A	G72D	0.999
1:183847657:T:C	L77P	0.999
1:183847669:T:C	L81P	0.999
1:183883894:T:C	L240P	0.999
1:183884730:T:C	F248S	0.999
1:183884753:T:C	C256R	0.999
1:183884755:C:G	C256W	0.999
1:183884768:T:A	W261R	0.999
1:183884768:T:C	W261R	0.999
1:183884770:G:C	W261C	0.999
1:183884770:G:T	W261C	0.999
1:183884856:T:A	V290D	0.999
1:183888477:T:C	C319R	0.999
1:183888479:T:G	C319W	0.999
1:183888494:T:A	N324K	0.999
1:183888494:T:G	N324K	0.999
1:183888495:T:C	F325L	0.999
1:183888497:T:A	F325L	0.999
1:183888497:T:G	F325L	0.999
1:183888526:T:C	L335P	0.999

dbSNP variants (sampled 300 via entrez): RS1000014628 (1:183755796 G>A), RS1000016091 (1:183785726 C>A,G,T), RS1000020277 (1:183792564 T>C), RS1000029863 (1:183720847 T>C,G), RS1000038890 (1:183844473 T>C), RS1000075133 (1:183655140 T>C), RS1000075581 (1:183695181 C>T), RS1000078339 (1:183704189 G>T), RS1000098589 (1:183811497 G>T), RS1000109599 (1:183720395 C>T), RS1000114329 (1:183823008 T>C), RS1000143850 (1:183794641 C>A), RS1000144481 (1:183876718 ATGTGTGTGTGTGTCT>A), RS1000150748 (1:183897258 G>C), RS1000153270 (1:183675878 G>A)

Disease associations

OMIM: gene MIM:605667 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000253_7	Attention deficit hyperactivity disorder and conduct disorder	9.000000e-06
GCST000643_5	Response to antidepressants	3.000000e-06
GCST004482_123	Peripheral arterial disease (traffic-related air pollution interaction)	8.000000e-06
GCST004482_124	Peripheral arterial disease (traffic-related air pollution interaction)	5.000000e-06
GCST004611_117	High light scatter reticulocyte count	1.000000e-10
GCST004612_156	High light scatter reticulocyte percentage of red cells	6.000000e-10
GCST004619_78	Reticulocyte fraction of red cells	1.000000e-11
GCST004622_139	Reticulocyte count	2.000000e-12
GCST004987_11	Antipsychotic drug-induced QTc interval change in schizophrenia	2.000000e-06
GCST005999_2	Aspartate aminotransferase levels	2.000000e-09
GCST006993_2	Hippocampal volume in Alzheimer’s disease dementia	3.000000e-07
GCST009959_21	Retinal detachment or retinal break	2.000000e-06
GCST011351_2	Aspartate aminotransferase levels	7.000000e-11
GCST90002385_101	High light scatter reticulocyte count	1.000000e-20
GCST90002386_387	High light scatter reticulocyte percentage of red cells	5.000000e-19
GCST90002387_236	Immature fraction of reticulocytes	5.000000e-10
GCST90002405_91	Reticulocyte count	3.000000e-18
GCST90002406_113	Reticulocyte fraction of red cells	1.000000e-16
GCST90011899_181	Aspartate aminotransferase levels	1.000000e-34
GCST90020028_271	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007908	traffic air pollution measurement
EFO:0007986	reticulocyte count
EFO:0008003	heart rate variability measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0005035	hippocampal volume
EFO:0010698	retinal break
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
bisphenol A	decreases methylation, increases expression	2
trichostatin A	increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
entinostat	increases expression	2
Vorinostat	increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	decreases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression, increases expression	1
chromium hexavalent ion	decreases expression	1
tacedinaline	increases expression	1
CGP 52608	affects binding, increases reaction	1
scriptaid	increases expression	1

Clinical trials (associated diseases)

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