RRAGB

Summary

RRAGB (Ras related GTP binding B, HGNC:19901) is a protein-coding gene on chromosome Xp11.21, encoding Ras-related GTP-binding protein B (Q5VZM2). Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.

Ras-homologous GTPases constitute a large family of signal transducers that alternate between an activated, GTP-binding state and an inactivated, GDP-binding state. These proteins represent cellular switches that are operated by GTP-exchange factors and factors that stimulate their intrinsic GTPase activity. All GTPases of the Ras superfamily have in common the presence of six conserved motifs involved in GTP/GDP binding, three of which are phosphate-/magnesium-binding sites (PM1-PM3) and three of which are guanine nucleotide-binding sites (G1-G3). Transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 10325 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_006064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19901
Approved symbol	RRAGB
Name	Ras related GTP binding B
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000083750
Ensembl biotype	protein_coding
OMIM	300725
Entrez	10325

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000262850, ENST00000374941, ENST00000414239, ENST00000474757, ENST00000475061, ENST00000498762, ENST00000892762, ENST00000922547, ENST00000922548, ENST00000959779, ENST00000959780, ENST00000959781

RefSeq mRNA: 4 — MANE Select: NM_006064 NM_001354011, NM_001354013, NM_006064, NM_016656

CCDS: CCDS14371, CCDS14372

Canonical transcript exons

ENST00000374941 — 10 exons

Exon	Start	End
ENSE00000671824	55751101	55751196
ENSE00000671826	55755841	55755932
ENSE00000893277	55731364	55731586
ENSE00000893280	55753392	55753514
ENSE00001257178	55722186	55722285
ENSE00001329971	55758246	55758774
ENSE00001465193	55717749	55718419
ENSE00003506865	55757216	55757331
ENSE00003515425	55719314	55719347
ENSE00003579890	55729294	55729360

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 94.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9292 / max 217.0966, expressed in 1786 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196476	13.2210	1780
196475	1.1185	733
196477	0.5897	329

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.33	gold quality
mucosa of stomach	UBERON:0001199	93.97	gold quality
left ovary	UBERON:0002119	92.67	gold quality
left lobe of thyroid gland	UBERON:0001120	92.42	gold quality
right ovary	UBERON:0002118	92.40	gold quality
cortical plate	UBERON:0005343	92.34	gold quality
right lung	UBERON:0002167	92.03	gold quality
adenohypophysis	UBERON:0002196	92.01	gold quality
tibial nerve	UBERON:0001323	91.98	gold quality
right uterine tube	UBERON:0001302	91.74	gold quality
right lobe of thyroid gland	UBERON:0001119	91.68	gold quality
endocervix	UBERON:0000458	91.63	gold quality
body of uterus	UBERON:0009853	91.55	gold quality
cerebellar hemisphere	UBERON:0002245	91.54	gold quality
popliteal artery	UBERON:0002250	91.43	gold quality
tibial artery	UBERON:0007610	91.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.40	gold quality
ectocervix	UBERON:0012249	91.36	gold quality
cerebellar cortex	UBERON:0002129	91.30	gold quality
right coronary artery	UBERON:0001625	91.17	gold quality
skin of leg	UBERON:0001511	91.09	gold quality
right adrenal gland cortex	UBERON:0035827	91.02	gold quality
skin of abdomen	UBERON:0001416	91.00	gold quality
left adrenal gland cortex	UBERON:0035825	90.88	gold quality
left uterine tube	UBERON:0001303	90.70	gold quality
aorta	UBERON:0000947	90.58	gold quality
left adrenal gland	UBERON:0001234	90.50	gold quality
descending thoracic aorta	UBERON:0002345	90.50	gold quality
metanephros cortex	UBERON:0010533	90.45	gold quality
thyroid gland	UBERON:0002046	90.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	237.68
E-ANND-3	yes	3.94
E-ENAD-17	no	773.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting RRAGB, 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-499A-5P	99.98	70.79	1323
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758

Literature-anchored findings (GeneRIF, showing 5)

• Inhibition of glutaminolysis prevents GTP loading of RagB and lysosomal translocation and subsequent activation of mTORC1. (PMID:22749528)
• Data suggest DNM2/RRAGB- (or DNM2/RRAGC-)dependent endocytosis of extracellular amino acids (AAs) plays critical role in mTORC1 transport/activation; recruitment of mTORC1 from cytoplasm to lysosome is suppressed by DNM2 inhibition; AA deprivation appears to be main cause of mTORC1 inactivation via DNM2 inhibition. (RHEB = Ras homolog enriched in brain; DNM2 = dynamin II; RRAG = Ras-related GTP binding protein) (PMID:28808055)
• Elevated Ras related GTP binding B (RRAGB) expression predicts poor overall survival and constructs a prognostic nomogram for colon adenocarcinoma. (PMID:34320917)
• Rag GTPases suppress PRL-3 degradation and predict poor clinical diagnosis of cancer patients with low PRL-3 mRNA expression. (PMID:34482023)
• circEXOC6B interacting with RRAGB, an mTORC1 activator, inhibits the progression of colorectal cancer by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop. (PMID:35739524)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rraga	ENSDARG00000104149
mus_musculus	Rragb	ENSMUSG00000041658
rattus_norvegicus	RragB	ENSRNOG00000062421
drosophila_melanogaster	RagA-B	FBGN0037647
caenorhabditis_elegans		WBGENE00006414

Paralogs (3): RRAGD (ENSG00000025039), RRAGC (ENSG00000116954), RRAGA (ENSG00000155876)

Protein

Protein identifiers

Ras-related GTP-binding protein B — Q5VZM2 (reviewed: Q5VZM2)

All UniProt accessions (2): Q5VZM2, Q5VZM0

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form: RagB/RRAGB is in its active form when GTP-bound RagB/RRAGB forms a complex with GDP-bound RagC/RRAGC (or RagD/RRAGD) and in an inactive form when GDP-bound RagB/RRAGB heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD). In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway.

Subunit / interactions. Interacts with RRAGC and RRAGD; heterodimerization stabilizes RRAG proteins. The GTP-bound form of RRAGB (in complex with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGB, is negatively regulated by amino acids and prevents interaction with RPTOR. Interacts with the GATOR1 complex; inactivates RRAGB. The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor. Interacts with SESN1, SESN2 and SESN3.

Subcellular location. Cytoplasm. Lysosome membrane.

Activity regulation. The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). The Ragulator complex functions as a GEF and promotes the active GTP-bound form. The GATOR1 complex functions as a GAP and stimulates RRAGB GTPase activity to turn it into its inactive GDP-bound form, preventing mTORC1 recruitment and activation.

Similarity. Belongs to the GTR/RAG GTP-binding protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VZM2-1	1, Long	yes
Q5VZM2-2	2, Short

RefSeq proteins (4): NP_001340940, NP_001340942, NP_006055, NP_057740 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006762	Gtr1_RagA	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR039397	RagA/B	Family

Pfam: PF04670

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (36 total): binding site 23, cross-link 4, mutagenesis site 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZM2-F1	82.50	0.70

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 (23): 53; 54; 54; 55; 55; 69; 69; 75; 75; 126; 188; 188 …

Post-translational modifications (5): 1, 203, 281, 291, 305

Mutagenesis-validated functional residues (3):

Position	Phenotype
54	decreased rptor-binding.
54	reduced affinity for all nucleotides, but with preferential binding of gdp over gtp.
127	maintains gtp-bound state. increased rptor-binding.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-165159	MTOR signalling
R-HSA-166208	mTORC1-mediated signalling
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9612973	Autophagy
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 112 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOMF_GTPASE_BINDING, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, USF_C, PID_MTOR_4PATHWAY, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, WCTCNATGGY_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, NKX22_01, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, GOBP_CELLULAR_RESPONSE_TO_STARVATION

GO Biological Process (9): intracellular protein localization (GO:0008104), cellular response to starvation (GO:0009267), negative regulation of autophagy (GO:0010507), regulation of TOR signaling (GO:0032006), positive regulation of TOR signaling (GO:0032008), cellular response to amino acid starvation (GO:0034198), cellular response to amino acid stimulus (GO:0071230), positive regulation of TORC1 signaling (GO:1904263), cellular response to leucine starvation (GO:1990253)

GO Molecular Function (7): GTPase activity (GO:0003924), GTP binding (GO:0005525), guanyl ribonucleotide binding (GO:0032561), GTPase binding (GO:0051020), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), Gtr1-Gtr2 GTPase complex (GO:1990131), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	2
MTOR signalling	2
Autophagy	1
Transcriptional Regulation by TP53	1
PTEN Regulation	1
Cellular response to starvation	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Generic Transcription Pathway	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
TOR signaling	2
macromolecule localization	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of intracellular signal transduction	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
cellular response to starvation	1
response to amino acid starvation	1
response to amino acid	1
cellular response to acid chemical	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
cellular response to amino acid starvation	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
guanyl nucleotide binding	1
purine ribonucleotide binding	1
enzyme binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
GTPase complex	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRAGB	RPTOR	Q8N122	995
RRAGB	RRAGC	Q9HB90	992
RRAGB	RRAGD	Q9NQL2	992
RRAGB	RHEB	Q15382	940
RRAGB	MTOR	P42345	886
RRAGB	RRAGA	Q7L523	884
RRAGB	RPS6KB1	P23443	854
RRAGB	FLCN	Q8NFG4	819
RRAGB	MLST8	Q9BVC4	798
RRAGB	SH3BP4	Q9P0V3	794
RRAGB	NPRL2	Q8WTW4	769
RRAGB	WDR24	Q96S15	759
RRAGB	NPRL3	Q12980	747
RRAGB	WDR59	Q6PJI9	742
RRAGB	RPS6	P08227	718

IntAct

65 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
RRAGC	RRAGB	psi-mi:“MI:0914”(association)	0.870
RRAGC	RRAGB	psi-mi:“MI:0915”(physical association)	0.870
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
RRAGB	RRAGC	psi-mi:“MI:0915”(physical association)	0.870
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860
RRAGB	LAMTOR1	psi-mi:“MI:0914”(association)	0.840
LAMTOR2	RRAGB	psi-mi:“MI:0914”(association)	0.790
RRAGC	LAMTOR5	psi-mi:“MI:0914”(association)	0.760
RRAGD	RRAGB	psi-mi:“MI:0914”(association)	0.740
RRAGD	RRAGB	psi-mi:“MI:0915”(physical association)	0.740
LAMTOR3	LAMTOR5	psi-mi:“MI:0914”(association)	0.730
RRAGB	SLC38A9	psi-mi:“MI:0915”(physical association)	0.670
RRAGB	LAMTOR5	psi-mi:“MI:0914”(association)	0.640

BioGRID (113): RRAGB (Affinity Capture-Western), LAMTOR3 (Affinity Capture-MS), LAMTOR2 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), RRAGB (Affinity Capture-Western), RRAGB (Affinity Capture-Western), RRAGB (Co-localization), RRAGB (Affinity Capture-Western), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS), RRAGB (Affinity Capture-MS)

ESM2 similar proteins: B1H1G2, B7ZC96, D4A6Z8, I1RE72, O18866, O18867, O35099, O54982, O75165, P11881, P17972, P29994, P29995, P70227, Q03720, Q08460, Q0E908, Q0IH22, Q12791, Q14571, Q14573, Q14643, Q21029, Q24498, Q28204, Q28265, Q5VZM2, Q62976, Q63269, Q63487, Q66HX8, Q6NTA4, Q6Z0E2, Q8AYS8, Q8JH92, Q8WN95, Q8WN96, Q8WSR4, Q8WZA2, Q90ZC7

Diamond homologs: O74824, Q00582, Q3SX43, Q54IK1, Q5VZM2, Q63486, Q63487, Q6NTA4, Q7L523, Q80X95, Q9SF92, P53290

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RRAGB	“form complex”	RAGBC	binding
RRAGB	“form complex”	RAGBD	binding
GATOR1	“down-regulates activity”	RRAGB	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
mTORC1-mediated signalling	9	119.0×	1e-15
Energy dependent regulation of mTOR by LKB1-AMPK	9	98.5×	5e-15
Amino acids regulate mTORC1	12	66.8×	1e-17
MTOR signalling	9	66.4×	2e-13
PTEN Regulation	9	57.1×	7e-13
Regulation of PTEN gene transcription	9	44.6×	6e-12
Cellular response to starvation	9	41.4×	1e-11
Autophagy	10	41.2×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
TORC1 signaling	5	83.6×	3e-07
positive regulation of TOR signaling	8	82.6×	6e-12
cellular response to amino acid stimulus	9	57.5×	6e-12
positive regulation of TORC1 signaling	9	55.4×	6e-12
intracellular protein localization	6	13.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
395718	GRCh37/hg19 Xp22.33-q28(chrX:70297-155246585)x1	Pathogenic

SpliceAI

1813 predictions. Top by Δscore:

Variant	Effect	Δscore
X:55722286:G:GG	donor_gain	1.0000
X:55729292:A:AG	acceptor_gain	1.0000
X:55729293:G:GA	acceptor_gain	1.0000
X:55729293:GTT:G	acceptor_gain	1.0000
X:55729357:GTGG:G	donor_gain	1.0000
X:55731359:A:AG	acceptor_gain	1.0000
X:55731359:ATCAG:A	acceptor_gain	1.0000
X:55731360:T:G	acceptor_gain	1.0000
X:55731360:TCA:T	acceptor_loss	1.0000
X:55731361:CA:C	acceptor_loss	1.0000
X:55731362:A:AG	acceptor_gain	1.0000
X:55731362:AG:A	acceptor_gain	1.0000
X:55731363:G:A	acceptor_loss	1.0000
X:55731363:G:GC	acceptor_gain	1.0000
X:55731363:GG:G	acceptor_gain	1.0000
X:55731363:GGC:G	acceptor_gain	1.0000
X:55731363:GGCA:G	acceptor_gain	1.0000
X:55731363:GGCAA:G	acceptor_gain	1.0000
X:55731582:ACCTG:A	donor_loss	1.0000
X:55731584:CTG:C	donor_loss	1.0000
X:55731585:TGG:T	donor_loss	1.0000
X:55731587:G:GG	donor_gain	1.0000
X:55731587:GTAA:G	donor_loss	1.0000
X:55731588:T:A	donor_loss	1.0000
X:55753386:T:TA	acceptor_gain	1.0000
X:55753387:GTTA:G	acceptor_loss	1.0000
X:55753388:TTAGG:T	acceptor_gain	1.0000
X:55753389:TA:T	acceptor_loss	1.0000
X:55753389:TAGG:T	acceptor_gain	1.0000
X:55753390:A:AG	acceptor_gain	1.0000

AlphaMissense

2319 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:55722190:T:C	L44P	1.000
X:55722193:T:C	L45S	1.000
X:55722198:G:A	G47S	1.000
X:55722198:G:C	G47R	1.000
X:55722198:G:T	G47C	1.000
X:55722199:G:A	G47D	1.000
X:55722199:G:T	G47V	1.000
X:55722213:G:A	G52S	1.000
X:55722213:G:C	G52R	1.000
X:55722213:G:T	G52C	1.000
X:55722214:G:A	G52D	1.000
X:55722214:G:T	G52V	1.000
X:55722216:A:C	K53Q	1.000
X:55722220:C:T	T54I	1.000
X:55722222:A:C	S55R	1.000
X:55722223:G:A	S55N	1.000
X:55722224:C:A	S55R	1.000
X:55722224:C:G	S55R	1.000
X:55722226:T:A	M56K	1.000
X:55722226:T:G	M56R	1.000
X:55722229:G:T	R57M	1.000
X:55722231:T:C	S58P	1.000
X:55722238:T:A	I60N	1.000
X:55722240:T:A	F61I	1.000
X:55722240:T:C	F61L	1.000
X:55722240:T:G	F61V	1.000
X:55722241:T:C	F61S	1.000
X:55722241:T:G	F61C	1.000
X:55722242:T:A	F61L	1.000
X:55722242:T:G	F61L	1.000

dbSNP variants (sampled 300 via entrez): RS1000251321 (X:55734785 G>A), RS1000274761 (X:55756899 G>T), RS1000480088 (X:55745273 A>G), RS1000553201 (X:55743188 A>G), RS1000622856 (X:55740499 T>G), RS1000677593 (X:55716115 A>G), RS1000700803 (X:55729827 G>A,T), RS1000726616 (X:55730391 A>G), RS1000740166 (X:55725300 T>C), RS1000881527 (X:55754400 G>A,T), RS1000922965 (X:55742432 TAA>T), RS1000964946 (X:55717861 C>G,T), RS1001132315 (X:55716408 G>A), RS1001312235 (X:55718346 G>A), RS1001360431 (X:55719963 C>T)

Disease associations

OMIM: gene MIM:300725 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002396_25	Smoking initiation	8.000000e-08
GCST003983_11	Male-pattern baldness	6.000000e-18
GCST004093_4	Prostate-specific antigen levels	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	increases expression	1
Folic Acid	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Rifampin	decreases expression	1
Silicon Dioxide	decreases expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
Zearalenone	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2E6	Abcam HeLa RRAGB KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms