GSPT2

Summary

GSPT2 (G1 to S phase transition 2, HGNC:4622) is a protein-coding gene on chromosome Xp11.22, encoding Eukaryotic peptide chain release factor GTP-binding subunit ERF3B (Q8IYD1). GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA.

This gene encodes a GTPase that belongs to the GTP-binding elongation factor family. The encoded protein is a polypeptide release factor that complexes with eukaryotic peptide chain release factor 1 to mediate translation termination. This protein may also be involved in mRNA stability.

Source: NCBI Gene 23708 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Limited, GenCC)
• Clinical variants (ClinVar): 43 total — 1 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018094

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4622
Approved symbol	GSPT2
Name	G1 to S phase transition 2
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	eRF3b, FLJ10441
Ensembl gene	ENSG00000189369
Ensembl biotype	protein_coding
OMIM	300418
Entrez	23708

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340438

RefSeq mRNA: 1 — MANE Select: NM_018094 NM_018094

CCDS: CCDS14336

Canonical transcript exons

ENST00000340438 — 1 exons

Exon	Start	End
ENSE00001377397	51743442	51746232

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2446 / max 152.9024, expressed in 1576 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196365	11.4522	1571
196366	0.6843	377
209685	0.1080	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.96	gold quality
male germ cell	CL:0000015	95.03	gold quality
cortical plate	UBERON:0005343	87.11	gold quality
germinal epithelium of ovary	UBERON:0001304	85.83	gold quality
choroid plexus epithelium	UBERON:0003911	85.76	gold quality
ventricular zone	UBERON:0003053	85.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.09	gold quality
ganglionic eminence	UBERON:0004023	84.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.66	gold quality
embryo	UBERON:0000922	84.01	gold quality
middle temporal gyrus	UBERON:0002771	83.85	gold quality
pigmented layer of retina	UBERON:0001782	83.48	gold quality
hair follicle	UBERON:0002073	82.87	gold quality
renal glomerulus	UBERON:0000074	82.83	gold quality
metanephric glomerulus	UBERON:0004736	82.53	gold quality
left ventricle myocardium	UBERON:0006566	82.42	gold quality
epithelial cell of pancreas	CL:0000083	82.01	gold quality
islet of Langerhans	UBERON:0000006	81.84	gold quality
palpebral conjunctiva	UBERON:0001812	81.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.26	gold quality
tibia	UBERON:0000979	81.19	gold quality
hypothalamus	UBERON:0001898	81.04	gold quality
heart right ventricle	UBERON:0002080	81.03	gold quality
cauda epididymis	UBERON:0004360	80.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.87	gold quality
CA1 field of hippocampus	UBERON:0003881	80.69	gold quality
parietal pleura	UBERON:0002400	80.63	gold quality
metanephros	UBERON:0000081	80.59	gold quality
pleura	UBERON:0000977	80.26	gold quality
endothelial cell	CL:0000115	80.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting GSPT2, 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-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 7)

• eRF3b can substitute for eRF3a in its translation termination function. (PMID:15987998)
• eRF1’s M domain contacts eRF3’s GTPase domain (PMID:19417105)
• The survivin and eRF3 complex may function in spindle formation and segregation of chromosomes and cytokinesis. (PMID:23377885)
• The tumor marker eRF3B can change the cell cycle and influence the phosphorylation status of 4E-BP1. (PMID:24466059)
• The proteolytic cleavage of eRF3a and eRF3b into p-eRF3 leads to release an amino-terminal fragment containing nuclear export signal to allow the relocalization of eRF3 into the nucleus to interact with the p14ARF. (PMID:24569073)
• Loss of GSPT2 and/or MAGED1 function may contribute to the intellectual disability. (PMID:28414775)
• eRF3b37 is thought to serve a role in hepatic stellate cells by inhibiting TGFbeta signaling. (PMID:30272252)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef2a.2	ENSDARG00000042065
danio_rerio	eef2a.1	ENSDARG00000042094
danio_rerio	eef1a1l3	ENSDARG00000071727
mus_musculus	Gspt2	ENSMUSG00000071723
rattus_norvegicus	Gspt2	ENSRNOG00000048817
drosophila_melanogaster	mEFTu2	FBGN0033184
drosophila_melanogaster	eIF2gamma	FBGN0263740
caenorhabditis_elegans	tufm-2	WBGENE00007001
caenorhabditis_elegans	eif-2gamma	WBGENE00021466

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EEFSEC (ENSG00000132394), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EEF1A1 (ENSG00000156508), EIF5B (ENSG00000158417), GFM2 (ENSG00000164347), EEF2 (ENSG00000167658), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), EIF2S3B (ENSG00000180574)

Protein

Protein identifiers

Eukaryotic peptide chain release factor GTP-binding subunit ERF3B — Q8IYD1 (reviewed: Q8IYD1)

Alternative names: G1 to S phase transition protein 2 homolog

All UniProt accessions (1): Q8IYD1

UniProt curated annotations — full annotation on UniProt →

Function. GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA. GSPT2/ERF3B mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. GTP hydrolysis by GSPT2/ERF3B induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.

Subunit / interactions. Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and ERF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with UPF1 and PABPC1.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in IUCC stage II colorectal cancer (CRC).

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.

RefSeq proteins (1): NP_060564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR004161	EFTu-like_2	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR009001	Transl_elong_EF1A/Init_IF2_C	Homologous_superfamily
IPR009818	PAM2_motif	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031157	G_TR_CS	Conserved_site
IPR050100	TRAFAC_GTPase_members	Family
IPR054696	GTP-eEF1A_C	Domain

Pfam: PF00009, PF03144, PF07145, PF22594

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (24 total): region of interest 8, sequence conflict 5, mutagenesis site 4, binding site 3, chain 1, domain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3KUJ	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYD1-F1	75.18	0.49

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 (3): 213–218; 349–352; 391–393

Mutagenesis-validated functional residues (4):

Position	Phenotype
52	impairs interaction with upf1 and pabpc1; when associated with a-55, k-56 and a-59.
55	impairs interaction with upf1 and pabpc1; when associated with k-52, k-56 and a-59.
56	impairs interaction with upf1 and pabpc1; when associated with k52, a-55, and a-59.
59	impairs interaction with upf1 and pabpc1; when associated with k-52, a-55 and k-56.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)

MSigDB gene sets: 157 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_TRANSLATIONAL_TERMINATION, GOBP_TRANSLATION, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, GROSS_HYPOXIA_VIA_ELK3_DN, GROSS_HYPOXIA_VIA_ELK3_ONLY_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GARY_CD5_TARGETS_DN, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, CTTTGTA_MIR524, REACTOME_METABOLISM_OF_RNA

GO Biological Process (3): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), translation (GO:0006412), translational termination (GO:0006415)

GO Molecular Function (7): RNA binding (GO:0003723), translation release factor activity (GO:0003747), GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytosol (GO:0005829), translation release factor complex (GO:0018444), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nonsense-Mediated Decay (NMD)	2
Translation	1
Signaling by ROBO receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
nuclear-transcribed mRNA catabolic process	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
protein-containing complex disassembly	1
nucleic acid binding	1
translation termination factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1483 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSPT2	ETF1	P46055	749
GSPT2	GTPBP4	Q9BZE4	725
GSPT2	CENPVL1	A0A0U1RR11	662
GSPT2	PABPC1	P11940	567
GSPT2	UPF1	Q92900	532
GSPT2	UPF3B	Q9BZI7	482
GSPT2	UPF2	Q9HAU5	479
GSPT2	PAIP1	Q9H074	472
GSPT2	PELO	Q9BRX2	466
GSPT2	SMG1	Q96Q15	439
GSPT2	BBS12	Q6ZW61	436
GSPT2	SMG6	Q86US8	414
GSPT2	GSTP1	P09211	407
GSPT2	WDR13	Q9H1Z4	402
GSPT2	ERFL	A0A1W2PQ73	400

IntAct

32 interactions, top by confidence:

A	B	Type	Score
PABPC1	GSPT2	psi-mi:“MI:0407”(direct interaction)	0.890
GSPT2	PABPC1	psi-mi:“MI:0914”(association)	0.890
GSPT2	PABPC1	psi-mi:“MI:0915”(physical association)	0.890
GSPT2	PABPC1	psi-mi:“MI:0407”(direct interaction)	0.890
UPF1	GSPT2	psi-mi:“MI:0915”(physical association)	0.680
ETF1	GSPT2	psi-mi:“MI:0915”(physical association)	0.670
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
PDE1C	PDE1A	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
SMG1	ETF1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GSPT1	EIF3CL	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (165): PAPSS2 (Co-fractionation), GSPT1 (Affinity Capture-MS), SRSF12 (Affinity Capture-MS), ETF1 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), PABPC4L (Affinity Capture-MS), CLK3 (Affinity Capture-MS), LARP1B (Affinity Capture-MS), CASC3 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS), PABPC1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), GSPT2 (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), MOV10 (Affinity Capture-MS)

ESM2 similar proteins: A8XGZ9, B5X2B8, B9FI63, F4INA9, F4J3R7, F4K2A1, F4K7F6, K7UTH7, O13861, O24310, O59683, O82497, O82626, O82653, P17745, P46199, P46280, P46577, Q09523, Q0WTB4, Q149F3, Q2KHZ2, Q40545, Q43117, Q5R4B3, Q5R6Y0, Q66GP9, Q69ZS7, Q6AXM7, Q6DCC6, Q6KAI0, Q6YPG5, Q710E8, Q84W56, Q8H0V1, Q8H1F6, Q8IYD1, Q8L607, Q8L7L0, Q8S4F6

Diamond homologs: A0RUM4, A1RXW9, A2BN41, A2Q0Z0, A3DMQ1, A5DPE3, A8ABM5, O13354, O24534, O42820, O49169, O64937, O74718, O93729, P02993, P05453, P06805, P08736, P0CN30, P0CN31, P0CT31, P0CT32, P0CT53, P0CT54, P0CT55, P0CY35, P0DH99, P10126, P13549, P14864, P14865, P14963, P15170, P17507, P17508, P17786, P23637, P25166, P25698, P28295

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	5	30.5×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	106.4×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
375379	NM_018094.5(GSPT2):c.1021G>A (p.Val341Ile)	Pathogenic

SpliceAI

80 predictions. Top by Δscore:

Variant	Effect	Δscore
X:51743612:GCAA:G	acceptor_gain	0.7300
X:51744015:TGGAA:T	acceptor_gain	0.5700
X:51744016:GGAAC:G	acceptor_gain	0.5300
X:51743611:A:AG	acceptor_gain	0.5100
X:51743612:G:GG	acceptor_gain	0.5100
X:51745082:G:T	acceptor_gain	0.5100
X:51744024:CAGAA:C	acceptor_gain	0.4700
X:51743513:T:A	donor_gain	0.4400
X:51743601:A:T	acceptor_gain	0.4300
X:51743506:C:G	donor_gain	0.4200
X:51743613:C:G	acceptor_gain	0.4000
X:51744089:GAA:G	donor_gain	0.3900
X:51743604:G:C	acceptor_gain	0.3800
X:51744092:G:GG	donor_gain	0.3800
X:51743607:A:C	acceptor_gain	0.3700
X:51744017:G:T	acceptor_gain	0.3700
X:51743612:GCA:G	acceptor_gain	0.3500
X:51743615:A:G	acceptor_gain	0.3500
X:51745080:TAG:T	acceptor_gain	0.3500
X:51743932:A:G	donor_gain	0.3400
X:51744025:AGAAC:A	acceptor_gain	0.3400
X:51744019:A:AT	acceptor_gain	0.3300
X:51743972:G:T	acceptor_gain	0.3100
X:51744023:TCAGA:T	acceptor_gain	0.3100
X:51744091:A:AG	donor_gain	0.3100
X:51743923:TCAAG:T	donor_loss	0.3000
X:51743924:CAAG:C	donor_loss	0.3000
X:51743925:AAGG:A	donor_loss	0.3000
X:51743926:AGGTA:A	donor_loss	0.3000
X:51743927:G:GA	donor_loss	0.3000

AlphaMissense

4133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:51744254:G:C	G210R	1.000
X:51744254:G:T	G210C	1.000
X:51744255:G:A	G210D	1.000
X:51744255:G:T	G210V	1.000
X:51744257:C:G	H211D	1.000
X:51744258:A:G	H211R	1.000
X:51744259:T:A	H211Q	1.000
X:51744259:T:G	H211Q	1.000
X:51744263:G:A	D213N	1.000
X:51744263:G:C	D213H	1.000
X:51744264:A:C	D213A	1.000
X:51744264:A:G	D213G	1.000
X:51744264:A:T	D213V	1.000
X:51744265:C:A	D213E	1.000
X:51744265:C:G	D213E	1.000
X:51744266:G:C	A214P	1.000
X:51744267:C:A	A214D	1.000
X:51744269:G:A	G215S	1.000
X:51744269:G:C	G215R	1.000
X:51744269:G:T	G215C	1.000
X:51744270:G:A	G215D	1.000
X:51744270:G:T	G215V	1.000
X:51744272:A:C	K216Q	1.000
X:51744272:A:G	K216E	1.000
X:51744273:A:T	K216M	1.000
X:51744274:G:C	K216N	1.000
X:51744274:G:T	K216N	1.000
X:51744275:T:C	S217P	1.000
X:51744276:C:T	S217L	1.000
X:51744279:C:T	T218I	1.000

dbSNP variants (sampled 300 via entrez): RS1000527151 (X:51741702 G>A), RS1002201205 (X:51743773 C>A), RS1006676488 (X:51745889 T>A,G), RS1006686358 (X:51745438 T>A,C), RS1009236888 (X:51742229 A>T), RS1009637865 (X:51742666 G>A,C), RS1016427000 (X:51743299 G>C), RS1016631272 (X:51745541 A>G,T), RS1019315035 (X:51742734 T>A), RS1020838998 (X:51744256 C>T), RS1022563596 (X:51746658 T>C), RS1023767169 (X:51741686 T>A), RS1025409638 (X:51746217 A>C,G), RS1025498372 (X:51743334 G>A,T), RS1029216472 (X:51742818 G>A)

Disease associations

OMIM: gene MIM:300418 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	X-linked

Mondo (2): autism (MONDO:0005260), intellectual disability (MONDO:0001071)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4105974 (SINGLE PROTEIN), CHEMBL6195537 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,642 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL572881	MOTESANIB	3	4,642

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	MOTESANIB

PubChem BioAssay actives

1 with measured affinity, of 59 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	1425015: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	affects methylation, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
arsenite	increases methylation	1
tetrabromobisphenol A	increases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Drugs, Chinese Herbal	increases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Phthalic Acids	decreases methylation	1
Tunicamycin	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991728	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1NW	HyCyte H4 KO-hGSPT2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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