FXR1

Summary

FXR1 (FMR1 autosomal homolog 1, HGNC:4023) is a protein-coding gene on chromosome 3q26.33, encoding RNA-binding protein FXR1 (P51114). mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis.

The protein encoded by this gene is an RNA binding protein that interacts with the functionally-similar proteins FMR1 and FXR2. These proteins shuttle between the nucleus and cytoplasm and associate with polyribosomes, predominantly with the 60S ribosomal subunit. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8087 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy, congenital, with respiratory insufficiency and bone fractures (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 94 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_005087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4023
Approved symbol	FXR1
Name	FMR1 autosomal homolog 1
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000114416
Ensembl biotype	protein_coding
OMIM	600819
Entrez	8087

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 27 protein_coding, 8 retained_intron, 1 nonsense_mediated_decay

ENST00000305586, ENST00000357559, ENST00000445140, ENST00000461044, ENST00000461801, ENST00000465551, ENST00000468861, ENST00000469882, ENST00000472339, ENST00000473375, ENST00000475315, ENST00000476672, ENST00000479176, ENST00000480918, ENST00000481383, ENST00000482125, ENST00000484042, ENST00000484790, ENST00000484958, ENST00000491062, ENST00000491674, ENST00000498658, ENST00000698793, ENST00000698794, ENST00000917910, ENST00000917911, ENST00000917912, ENST00000917913, ENST00000917914, ENST00000917915, ENST00000917916, ENST00000917917, ENST00000917918, ENST00000963215, ENST00000963216, ENST00000963217

RefSeq mRNA: 4 — MANE Select: NM_005087 NM_001013438, NM_001013439, NM_001363882, NM_005087

CCDS: CCDS3238, CCDS33894, CCDS46965, CCDS87169

Canonical transcript exons

ENST00000357559 — 17 exons

Exon	Start	End
ENSE00003468094	180963028	180963090
ENSE00003475128	180951298	180951468
ENSE00003529678	180948721	180948814
ENSE00003554139	180968051	180968254
ENSE00003562760	180961468	180961554
ENSE00003569775	180957819	180957928
ENSE00003586090	180970158	180970358
ENSE00003586104	180953762	180953840
ENSE00003590398	180949227	180949343
ENSE00003606345	180975313	180975404
ENSE00003677555	180935138	180935231
ENSE00003678861	180962883	180962940
ENSE00003684150	180948347	180948495
ENSE00003689428	180947865	180947936
ENSE00003974788	180912670	180912736
ENSE00003974789	180933334	180933386
ENSE00003974790	180976122	180982753

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 130.2860 / max 2352.0944, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39963	125.9339	1817
39961	4.1679	1412
39959	0.1465	60
39960	0.0273	4
39962	0.0105	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.37	gold quality
gastrocnemius	UBERON:0001388	99.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.23	gold quality
biceps brachii	UBERON:0001507	99.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.21	gold quality
muscle of leg	UBERON:0001383	99.19	gold quality
male germ cell	CL:0000015	99.14	gold quality
triceps brachii	UBERON:0001509	99.04	gold quality
gluteal muscle	UBERON:0002000	98.93	gold quality
ventricular zone	UBERON:0003053	98.88	gold quality
left testis	UBERON:0004533	98.76	gold quality
adrenal tissue	UBERON:0018303	98.73	gold quality
right testis	UBERON:0004534	98.72	gold quality
calcaneal tendon	UBERON:0003701	98.66	gold quality
diaphragm	UBERON:0001103	98.62	gold quality
muscle organ	UBERON:0001630	98.59	gold quality
skeletal muscle organ	UBERON:0014892	98.59	gold quality
ganglionic eminence	UBERON:0004023	98.52	gold quality
colonic epithelium	UBERON:0000397	98.22	gold quality
body of tongue	UBERON:0011876	98.20	gold quality
tendon	UBERON:0000043	98.09	gold quality
testis	UBERON:0000473	98.02	gold quality
embryo	UBERON:0000922	97.99	gold quality
vastus lateralis	UBERON:0001379	97.71	gold quality
stromal cell of endometrium	CL:0002255	97.66	gold quality
cranial nerve II	UBERON:0000941	97.63	gold quality
left ovary	UBERON:0002119	97.63	gold quality
skeletal muscle tissue	UBERON:0001134	97.57	gold quality
body of pancreas	UBERON:0001150	97.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

287 targeting FXR1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 40)

• Fxr1p shows a more tissue-specific expression particularly during late embryonic development. (PMID:15968590)
• Results show that three genes, namely FXR1, CLAPM1 and EIF4G, are most frequently overexpressed in the center of the amplified domain in squamous cell carcinomas. (PMID:17290396)
• A crosslinking-coupled affinity purification method was used to isolate TNF-alpha AU-rich element-associated proteins: two microRNP-related proteins, FXR1 and AGO2 were found that associate during translation activation. (PMID:17382880)
• FXR1 mRNA splicing pattern is altered in facioscapulohumeral muscular dystrophy myoblasts. (PMID:18628314)
• FXR1P and FXR2P KH2 domains bind G-quadruplex and kissing complex RNA with the same affinity as the FMRP KH2 domain. (PMID:19487368)
• These results indicate that FMR1 gene function is evolutionarily conserved in neural mechanisms and cannot be compensated by either FXR1 or FXR2, but that all three proteins can substitute for each other in non-neuronal requirements. (PMID:20442204)
• Data show that the nuclear localization signals of the FXR1 and FXR2 comprise tandem Tudor domain architectures. (PMID:21072162)
• Our study describes a novel role of FXR1P that has crucial implications for the understanding of its role during myogenesis and muscle development (PMID:23555284)
• FXR1 and UPF1 may have a functional role in prostate cancer progression and metastasis. (PMID:23881279)
• Deregulation of Fragile X-related protein 1 by the lipodystrophic lamin A p.R482W mutation elicits a myogenic gene expression program in preadipocytes. (PMID:24108105)
• findings showed that FXR1P interacts with BTF in vivo and proved that FXR1P and BTF can co-localize mainly in the cytoplasm around the nucleus (PMID:24389646)
• binding of PKP1/3 to FXR1 was RNA independent, and both PKP3 and FXR1 stabilized PKP2 mRNA. (PMID:25225333)
• The mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms, were identified. (PMID:25733852)
• FXR1P is a GSK3beta substrate with a role in regulating mood and emotion processing (PMID:26240334)
• An accumulation of 8 SNPs in the fragile gene family (FMR1, FXR1 and FXR2)were found associated with autistic traits in a sample of male patients. (PMID:26612855)
• P97 interacts with 3’ UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5’ caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions. (PMID:26942679)
• These data reveal a new role of FXR1 in controlling induction of monocyte migration. (PMID:27229378)
• FXR1P interacts with CMAS, and that FXR1P may enhance the activation of sialic acid via interaction with CMAS, and increase GM1 levels to affect the development of the nervous system, thus providing evidence for further research into the pathogenesis of FXS. (PMID:27357083)
• FXR1 binds and destabilizes p21 mRNA, binds and stabilizes TERC RNA and suppresses the cellular senescence in oral cancer cells. (PMID:27606879)
• human microbiota was able to reduce the levels of tauro-beta-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota (PMID:27956475)
• in colorectal cancers (CRC) and gastric cancers (GC) FXR1 somatic mutation that was a deletion (c.116delA (p. Asn391IlefsX14)) within the repeat was found; The mutation was detected in CRCs and GCs with MSI-H, but not in GCs and CRCs with MSS/MSI-L (PMID:28028731)
• Our findings support our a priori hypothesis of a possible interaction between GSK3B (rs12630592 T allele) and FXR1 (rs496250 A allele) in mood disorder patients. (PMID:28242499)
• Inhibition of the remaining family member FXR1 selectively blocks cell proliferation in human cancer cells containing homozygous deletion of both TP53 and FXR2 in a collateral lethality manner. (PMID:28767039)
• In dilated cardiomyopathy, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling and increasing cardiac arrhythmogenesis. (PMID:29101288)
• in head and neck squamous cell carcinoma, fragile X mental retardation syndrome related protein 1 (Fxr1) overexpression correlates with reduced F-box protein 4 (Fbxo4) levels. (PMID:29142209)
• FXR1 mRNA expression levels were significantly decreased in trophoblasts from recurrent miscarriage patients compared with healthy controls. FXR1 was highly expressed in human placental villi during early pregnancy. overexpression of FXR1 enhanced vascular endothelial growth factor-A and interleukin-8 expression in HTR-8 cells, whereas conversely, knockdown of FXR1 effectively repressed these effects. (PMID:29852926)
• The expression of downstream processes corroborates active PPARalpha signaling in LSECs. We uncover transcriptional evidence in LSECs for a feedback mechanism between PPARalpha and farnesoid X-activated receptor (FXR) that maintains bile acid homeostasis; previously, this feedback was known occur only in HepG2 cells. (PMID:30054499)
• FXR1 destabilizes pro-inflammatory transcripts in vascular smooth muscle. FXR1 binds canonical and non-canonical sequences in the 3’ UTR of TNFalpha. FXR1 interacts with HuR via mRNA tethering on the 3’ UTR of inflammatory transcripts. (PMID:30067974)
• High FXR1 expression is associated with glioma via stabilizing MIR17HG. (PMID:30691465)
• FXR1 negatively regulated FBXO4 transcripts via direct association with its 3’UTR prostate cancer cell lines. (PMID:30746571)
• Data show that recessive mutations in the particular exon of RNA binding proteins (FXR1P; FXR1) cause congenital multi-minicore myopathy in humans and mice. (PMID:30770808)
• Quantitative study in Wilms tumor of fragile X mental retardation autosomal homolog 1 (FXR1) expression in kidney of adult, fetal and wild type specimens. (PMID:30894247)
• FXR1 acts as a stabilizing factor for miR301a-3p against PNPT1 in oral cancer cells. (PMID:31940341)
• FXR1 is a novel MRE11-binding partner and participates in oxidative stress responses. (PMID:32211858)
• FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. (PMID:32328638)
• Spatial control of nucleoporin condensation by fragile X-related proteins. (PMID:32706158)
• Fragile X-related protein family: a double-edged sword in neurodevelopmental disorders and cancer. (PMID:32878499)
• Circ_0000079 Decoys the RNA-Binding Protein FXR1 to Interrupt Formation of the FXR1/PRCKI Complex and Decline Their Mediated Cell Invasion and Drug Resistance in NSCLC. (PMID:32951448)
• Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand. (PMID:33046820)
• circNRIP1 facilitates keloid progression via FXR1mediated upregulation of miR5033p and miR5035p. (PMID:33649815)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fxr1	ENSDARG00000022968
mus_musculus	Fxr1	ENSMUSG00000027680
rattus_norvegicus	Fxr1	ENSRNOG00000051480
rattus_norvegicus		ENSRNOG00000084292
drosophila_melanogaster	Fmr1	FBGN0028734

Paralogs (2): FMR1 (ENSG00000102081), FXR2 (ENSG00000129245)

Protein

Protein identifiers

RNA-binding protein FXR1 — P51114 (reviewed: P51114)

Alternative names: FMR1 autosomal homolog 1, hFXR1p

All UniProt accessions (14): A0A8V8TM97, A0A8V8TMQ1, A0A8V8TNP6, B4DXZ6, C9IZ22, C9J5B4, C9JAJ4, P51114, C9JY20, C9JYQ6, C9JZE0, E7EU85, E9PFF5, H7C4S4

UniProt curated annotations — full annotation on UniProt →

Function. mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis. Specifically binds to AU-rich elements (AREs) in the 3’-UTR of target mRNAs. Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors. Required to activate translation of stored mRNAs during late spermatogenesis: acts by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules that recruit translation initiation factor EIF4G3 to activate translation of stored mRNAs in late spermatids. Promotes translation of MYC transcripts by recruiting the eIF4F complex to the translation start site. Acts as a negative regulator of inflammation in response to IL19 by promoting destabilization of pro-inflammatory transcripts. Also acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing TNF protein production. Acts as a negative regulator of AMPA receptor GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting its translation. Regulates proliferation of adult neural stem cells by binding to CDKN1A mRNA and promoting its expression. Acts as a regulator of sleep and synaptic homeostasis by regulating translation of transcripts in neurons. Required for embryonic and postnatal development of muscle tissue by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules. Involved in the nuclear pore complex localization to the nuclear envelope by preventing cytoplasmic aggregation of nucleoporins: acts by preventing ectopic phase separation of nucleoporins in the cytoplasm via a microtubule-dependent mechanism. Plays a role in the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with PKP3. May also do the same for PKP2, PKP3 and DSP via its interaction with PKP1. Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates, crucial for processes like actomyosin reorganization.

Subunit / interactions. Homodimer (via CC domains); homodiremization is required for FXR1-network nucleation. Interacts with FMR1. Interacts with FRX2. Interacts with TDRD3. Interacts with HABP4. Interacts with CYFIP2 but not with CYFIP1. Interacts with EIF4G3; promoting translation of target mRNAs. Interacts with ELAVL1. Interacts with CEP63; inhibiting ‘Lys-63’-linked ubiquitination. Interacts with PKP3; the interaction facilitates the binding of PKP3 to PKP2 mRNA. Interacts with PKP1; the interaction may facilitate the binding of PKP1 to PKP2, PKP3 and DSP mRNA. (Microbial infection) Interacts with Sindbis virus non-structural protein 3 (via C-terminus); this interaction inhibits the formation of host stress granules on viral mRNAs and the nsp3-FXR1 complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes.

Subcellular location. Cytoplasm. Cytoplasmic ribonucleoprotein granule. Stress granule. Cell projection. Dendrite. Dendritic spine. Axon. Nucleus envelope. Postsynapse.

Tissue specificity. Expressed in all tissues examined including heart, brain, kidney and testis. In brain, present at high level in neurons and especially in the Purkinje cells at the interface between the granular layer and the molecular layer (at protein level).

Post-translational modifications. Phosphorylation at Ser-420 by PAK1 promotes its relocalization to stress granules and activity. Phosphorylated by MAPK1/ERK2, promoting subsequent phosphorylation by GSK3B. Phosphorylated by GSK3B, promoting ubiquitination and degradation by the proteasome. Ubiquitinated by the SCF(FBXO4) complex, leading to its degradation by the proteasome: ubiquitination by the SCF(FBXO4) complex takes place following phosphorylation by GSK3B. Ubiquitinated and degraded in a GSK3B-dependent manner in during both scaling and sleep deprivation. Ubiquitinated via ‘Lys-63’-linked ubiquitin, leading to its degradation: interaction with CEP63 inhibits ‘Lys-63’-linked ubiquitination.

Disease relevance. Congenital myopathy 9A (CMYO9A) [MIM:618822] An autosomal recessive muscular disorder characterized by severe hypotonia apparent at birth, poor feeding, ulnar deviation of the hands, laterally deviated feet, fractures of the long bones, respiratory insufficiency due to muscle weakness, and death in infancy. The disease is caused by variants affecting the gene represented in this entry. Congenital myopathy 9B, proximal, with minicore lesions (CMYO9B) [MIM:618823] An autosomal recessive, slowly progressive muscular disorder characterized by primarily proximal muscle weakness, neonatal hypotonia leading to delayed motor development, mildly delayed walking in childhood, and difficulty running or climbing. Cardiac function is unaffected, but most patients have obstructive sleep apnea. Muscle biopsy shows type 1 fiber predominance with disorganized Z-lines and minicores that disrupt the myofibrillar striation pattern. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The tandem Agenet-like domains preferentially recognize trimethylated histone peptides. Disordered region at the C-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that stores mRNAs. CC1 and CC2 domains are required for homodimerization and FXR1-network nucleation. CC domains also mediate interaction with other proteins containing similar CC domains.

Induction. By Interleukin-19 (IL19).

Similarity. Belongs to the FMR1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51114-1	1, Long	yes
P51114-2	2, b, Short
P51114-3	3

RefSeq proteins (4): NP_001013456, NP_001013457, NP_001350811, NP_005078* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR008395	Agenet-like_dom	Domain
IPR022034	FMR1-like_C_core	Domain
IPR032172	FXR1_C1	Domain
IPR032177	FXR_C3	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR040148	FMR1	Family
IPR040472	FMRP_KH0	Domain
IPR041560	Tudor_FRM1	Domain
IPR047425	Tudor_Agenet_FXR1_rpt1	Domain
IPR047427	Tudor_Agenet_FXR1_rpt2	Domain
IPR047494	KH_I_FXR1_rpt1	Domain
IPR047495	KH_I_FXR1_rpt2	Domain
IPR047496	KH_I_FXR1_rpt3	Domain

Pfam: PF00013, PF05641, PF12235, PF16096, PF16097, PF17904, PF18336

UniProt features (75 total): modified residue 22, strand 13, mutagenesis site 8, compositionally biased region 6, region of interest 5, helix 5, domain 4, splice variant 3, sequence variant 3, sequence conflict 2, initiator methionine 1, chain 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3O8V	X-RAY DIFFRACTION	2.5
3KUF	X-RAY DIFFRACTION	2.7
2CPQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51114-F1	70.86	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 (23): 2, 68, 401, 403, 406, 409, 420, 423, 432, 447, 447, 453, 453, 455, 455, 483, 485, 524, 587, 611 …

Mutagenesis-validated functional residues (8):

Position	Phenotype
202	loss of rna-binding. disrupts fxr1-network.
266	loss of rna-binding. disrupts fxr1-network.
304	abolished binding to pak1. loss of rna-binding. disrupts fxr1-network.
345–346	does not affect binding to pak1.
348–352	abolished binding to pak1.
352–353	reduced binding to pak1.
420	abolished phosphorylation by pak1, leading to impaired activity.
420	mimics phosphorylation state; leading to increased activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions

MSigDB gene sets: 454 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_DENTATE_GYRUS_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HONMA_DOCETAXEL_RESISTANCE, GOBP_BEHAVIOR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, AMIT_EGF_RESPONSE_60_HELA, GCM_NPM1, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, YANG_BREAST_CANCER_ESR1_LASER_DN

GO Biological Process (31): apoptotic process (GO:0006915), spermatid development (GO:0007286), muscle organ development (GO:0007517), negative regulation of translation (GO:0017148), dentate gyrus development (GO:0021542), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of Rho protein signal transduction (GO:0035025), regulation of mRNA stability (GO:0043488), regulation of circadian sleep/wake cycle, sleep (GO:0045187), positive regulation of translation (GO:0045727), positive regulation of long-term neuronal synaptic plasticity (GO:0048170), animal organ development (GO:0048513), negative regulation of inflammatory response (GO:0050728), regulation of neurogenesis (GO:0050767), mRNA transport (GO:0051028), nuclear pore complex assembly (GO:0051292), nuclear pore localization (GO:0051664), regulation of synaptic transmission, glutamatergic (GO:0051966), skeletal muscle organ development (GO:0060538), mRNA destabilization (GO:0061157), regulation of translation at presynapse, modulating synaptic transmission (GO:0099577), membraneless organelle assembly (GO:0140694), negative regulation of long-term synaptic potentiation (GO:1900272), negative regulation of mRNA catabolic process (GO:1902373), positive regulation of miRNA-mediated gene silencing (GO:2000637), cytoplasmic translational initiation (GO:0002183), regulation of translation (GO:0006417), spermatogenesis (GO:0007283), post-transcriptional regulation of gene expression (GO:0010608), cell differentiation (GO:0030154), muscle structure development (GO:0061061)

GO Molecular Function (12): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), RNA strand annealing activity (GO:0033592), mRNA 3’-UTR AU-rich region binding (GO:0035925), protein homodimerization activity (GO:0042803), ribonucleoprotein complex binding (GO:0043021), translation regulator activity (GO:0045182), protein heterodimerization activity (GO:0046982), molecular condensate scaffold activity (GO:0140693), nucleic acid binding (GO:0003676), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (22): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), axon (GO:0030424), cytoplasmic ribonucleoprotein granule (GO:0036464), neuron projection (GO:0043005), costamere (GO:0043034), dendritic spine (GO:0043197), intracellular membraneless organelle (GO:0043232), perinuclear region of cytoplasm (GO:0048471), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), dendrite (GO:0030425), ribonucleoprotein granule (GO:0035770), cell projection (GO:0042995), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
regulation of translation	3
intracellular membraneless organelle	3
cytoplasm	3
translation	2
negative regulation of gene expression	2
anatomical structure development	2
protein dimerization activity	2
binding	2
intracellular anatomical structure	2
neuron projection	2
synapse	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
germ cell development	1
spermatid differentiation	1
animal organ development	1
muscle structure development	1
negative regulation of protein metabolic process	1
hippocampus development	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
regulation of circadian sleep/wake cycle	1
circadian sleep/wake cycle, sleep	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
regulation of long-term neuronal synaptic plasticity	1
positive regulation of neurogenesis	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
neurogenesis	1

Protein interactions and networks

STRING

2840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FXR1	CYFIP1	Q7L576	996
FXR1	CYFIP2	Q96F07	996
FXR1	AGO2	Q9UKV8	993
FXR1	NUFIP1	Q9UHK0	959
FXR1	FXR2	P51116	956
FXR1	DICER1	Q9UPY3	940
FXR1	PUF60	Q9UHX1	928
FXR1	HNRNPK	P61978	923
FXR1	PKP3	Q9Y446	918
FXR1	CPEB1	Q9BZB8	889
FXR1	PURA	Q00577	873
FXR1	G3BP1	Q13283	872
FXR1	NUFIP2	Q7Z417	846
FXR1	YBX1	P16990	843
FXR1	KCNG1	Q9UIX4	831

IntAct

422 interactions, top by confidence:

A	B	Type	Score
FXR1	FMR1	psi-mi:“MI:0915”(physical association)	0.800
FXR2	FXR1	psi-mi:“MI:0915”(physical association)	0.790
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
FXR2	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
UBAP2L	FXR1	psi-mi:“MI:0914”(association)	0.550
HSPB1	FXR1	psi-mi:“MI:0915”(physical association)	0.550
LUC7L2	FXR1	psi-mi:“MI:0915”(physical association)	0.550
CDK18	UBL4A	psi-mi:“MI:0914”(association)	0.530
PLEKHO1	UBA6	psi-mi:“MI:0914”(association)	0.530
MAGEA4	MAGEB16	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
ANKRD40	FXR1	psi-mi:“MI:0915”(physical association)	0.510
AP2M1	FXR1	psi-mi:“MI:0915”(physical association)	0.510
CDYL	FXR1	psi-mi:“MI:0915”(physical association)	0.510
CEP72	FXR1	psi-mi:“MI:0915”(physical association)	0.510
EML1	FXR1	psi-mi:“MI:0915”(physical association)	0.510
FLNA	FXR1	psi-mi:“MI:0915”(physical association)	0.510
KCTD13	FXR1	psi-mi:“MI:0915”(physical association)	0.510
KAZN	FXR1	psi-mi:“MI:0915”(physical association)	0.510
NONO	FXR1	psi-mi:“MI:0915”(physical association)	0.510
PHLDB1	FXR1	psi-mi:“MI:0915”(physical association)	0.510
RABAC1	FXR1	psi-mi:“MI:0915”(physical association)	0.510
TP53	FXR1	psi-mi:“MI:0915”(physical association)	0.510
TUBB	FXR1	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (866): FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Two-hybrid), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), FXR1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM64, A0JMV4, A2VDN6, A4IFB1, A4IGK4, D3ZTQ1, O70523, O75400, P35922, P51113, P51114, P51115, P70501, P98175, Q06787, Q12872, Q15459, Q2KHP9, Q2KIA6, Q2NLB0, Q2TBT7, Q3TCX3, Q3USH5, Q5BJ56, Q5R539, Q5R9B4, Q5SFM8, Q5T8P6, Q5XI81, Q61584, Q66I22, Q6DDU9, Q6GLC9, Q6NZ18, Q6NZN0, Q7TN31, Q80TJ7, Q80WE1, Q8CGC4, Q8JZX4

Diamond homologs: F1QLR3, O70523, P35922, P51113, P51114, P51115, P51116, Q06787, Q2KHP9, Q2TBT7, Q5BJ56, Q5R9B4, Q5XI81, Q61584, Q6GLC9, Q7ZTQ5, Q80WE1, Q9NFU0, Q9WVR4, A4WWP0, A5E870, A5VTB6, A6UF34, A7HZ97, A9M9Z8, B0CK15, B2S9G0, B9JGS9, C0RG51, C3MC71, Q07V82, Q11BC3, Q1QS60, Q2YQR3, Q57A96, Q8FXS9, Q8YEB7, Q92SW0, Q13EM2, Q89WB3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FBXO4	“down-regulates quantity by destabilization”	FXR1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	FXR1	polyubiquitination
PAK1	“up-regulates activity”	FXR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 220 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
Signaling by RAS mutants	5	16.0×	2e-03
HSF1-dependent transactivation	5	12.0×	5e-03
Assembly and cell surface presentation of NMDA receptors	6	11.5×	2e-03
Signaling by RAF1 mutants	5	10.6×	6e-03
Signaling by moderate kinase activity BRAF mutants	5	9.6×	6e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	9.6×	6e-03
Signaling downstream of RAS mutants	5	9.6×	6e-03
Oncogenic MAPK signaling	5	9.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	49
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2443948	NM_005087.4(FXR1):c.1603+733dup	Pathogenic
2443949	NM_005087.4(FXR1):c.1603+725dup	Pathogenic
828056	NM_005087.4(FXR1):c.1603+790_1603+793del	Pathogenic
986754	GRCh37/hg19 3q26.33(chr3:180102701-181991155)x1	Pathogenic
996580	NM_005087.4(FXR1):c.1772T>A (p.Ile591Asn)	Likely pathogenic

SpliceAI

2835 predictions. Top by Δscore:

Variant	Effect	Δscore
3:180933332:AG:A	acceptor_gain	1.0000
3:180933333:GG:G	acceptor_gain	1.0000
3:180933382:AATAA:A	donor_gain	1.0000
3:180933383:A:AG	donor_gain	1.0000
3:180933383:A:G	donor_gain	1.0000
3:180933383:ATAA:A	donor_loss	1.0000
3:180933384:TAA:T	donor_gain	1.0000
3:180933386:AG:A	donor_loss	1.0000
3:180933387:G:C	donor_loss	1.0000
3:180933387:G:GG	donor_gain	1.0000
3:180933388:T:G	donor_loss	1.0000
3:180935133:TTCA:T	acceptor_loss	1.0000
3:180935134:TCAGT:T	acceptor_loss	1.0000
3:180935136:A:AG	acceptor_gain	1.0000
3:180935136:AGTT:A	acceptor_gain	1.0000
3:180935136:AGTTG:A	acceptor_gain	1.0000
3:180935137:G:GG	acceptor_gain	1.0000
3:180935137:GTT:G	acceptor_gain	1.0000
3:180935137:GTTG:G	acceptor_gain	1.0000
3:180935137:GTTGG:G	acceptor_gain	1.0000
3:180935229:GAG:G	donor_gain	1.0000
3:180935230:AGG:A	donor_loss	1.0000
3:180935232:G:GA	donor_loss	1.0000
3:180935232:G:GG	donor_gain	1.0000
3:180935233:T:G	donor_loss	1.0000
3:180947932:GAGAA:G	donor_gain	1.0000
3:180947933:AGAA:A	donor_gain	1.0000
3:180947934:GAA:G	donor_gain	1.0000
3:180947934:GAAG:G	donor_gain	1.0000
3:180947935:AAGTA:A	donor_loss	1.0000

AlphaMissense

4089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:180912704:G:A	E7K	1.000
3:180912713:G:C	G10R	1.000
3:180912722:G:A	G13R	1.000
3:180912722:G:C	G13R	1.000
3:180912722:G:T	G13W	1.000
3:180912723:G:A	G13E	1.000
3:180912723:G:T	G13V	1.000
3:180912726:C:A	A14D	1.000
3:180912731:T:C	Y16H	1.000
3:180912731:T:G	Y16D	1.000
3:180933334:G:A	G18R	1.000
3:180933334:G:C	G18R	1.000
3:180933335:G:A	G18E	1.000
3:180933365:T:C	L28P	1.000
3:180933371:T:A	V30D	1.000
3:180933376:T:A	F32I	1.000
3:180933376:T:C	F32L	1.000
3:180933377:T:C	F32S	1.000
3:180933377:T:G	F32C	1.000
3:180933378:T:A	F32L	1.000
3:180933378:T:G	F32L	1.000
3:180935139:T:A	W36R	1.000
3:180935139:T:C	W36R	1.000
3:180935140:G:C	W36S	1.000
3:180935141:G:C	W36C	1.000
3:180935141:G:T	W36C	1.000
3:180935158:T:A	V42D	1.000
3:180935173:T:A	V47D	1.000
3:180935175:A:G	R48G	1.000
3:180935176:G:C	R48T	1.000

dbSNP variants (sampled 300 via entrez): RS1000019707 (3:180970421 T>A,C), RS1000025176 (3:180955438 C>A,T), RS1000049513 (3:180929422 G>A,C), RS1000054324 (3:180916086 C>T), RS1000119547 (3:180953236 A>G), RS1000188742 (3:180910818 T>C), RS1000279302 (3:180961968 A>G), RS1000343377 (3:180935374 C>T), RS1000409648 (3:180940870 G>A), RS1000422671 (3:180943929 T>A), RS1000497505 (3:180970786 C>T), RS1000499837 (3:180913339 T>G), RS1000527538 (3:180965722 A>G), RS1000571759 (3:180911734 A>G), RS1000583887 (3:180913170 C>T)

Disease associations

OMIM: gene MIM:600819 | disease phenotypes: MIM:618823, MIM:618822, MIM:117000, MIM:206900

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy, congenital proximal, with minicore lesions	Strong	Autosomal recessive
myopathy, congenital, with respiratory insufficiency and bone fractures	Strong	Autosomal recessive
congenital myopathy	Strong	Autosomal recessive

Mondo (7): scoliosis (MONDO:0005392), myopathy, congenital proximal, with minicore lesions (MONDO:0032937), myopathy, congenital, with respiratory insufficiency and bone fractures (MONDO:0032936), multiminicore myopathy (MONDO:0018948), congenital myopathy (MONDO:0019952), anophthalmia/microphthalmia-esophageal atresia syndrome (MONDO:0008799), intellectual disability (MONDO:0001071)

Orphanet (4): Multiminicore myopathy (Orphanet:598), Congenital myopathy (Orphanet:97245), Anophthalmia/microphthalmia-esophageal atresia syndrome (Orphanet:77298), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

21 total (22 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000050	Hypoplastic male external genitalia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001308	Tongue fasciculations
HP:0001319	Neonatal hypotonia
HP:0001513	Obesity
HP:0001522	Death in infancy
HP:0001558	Decreased fetal movement
HP:0001562	Oligohydramnios
HP:0002304	Akinesia
HP:0002870	Obstructive sleep apnea
HP:0003458	EMG: myopathic abnormalities
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003701	Proximal muscle weakness
HP:0003789	Minicore myopathy
HP:0003803	Type 1 muscle fiber predominance
HP:0004322	Short stature
HP:0012548	Fatty replacement of skeletal muscle
HP:0020203	Z-band streaming
HP:0002650	Scoliosis

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000434_4	Schizophrenia	1.000000e-07
GCST002539_51	Schizophrenia	2.000000e-08
GCST003132_2	Eating disorder in bipolar disorder	4.000000e-06
GCST003135_3	Bipolar disorder and eating disorder	1.000000e-06
GCST006803_33	Schizophrenia	3.000000e-12
GCST007201_214	Schizophrenia	1.000000e-09
GCST008595_41	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	8.000000e-09
GCST009391_2115	Metabolite levels	8.000000e-06
GCST011383_10	Mastocytosis	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010381	phosphatidylcholine 36:3 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D012600	Scoliosis	C05.116.900.800.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879858 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.71	Kd	1.973	nM	CHEMBL5653589
8.71	ED50	1.973	nM	CHEMBL5653589
8.02	Kd	9.572	nM	CHEMBL3752910
8.02	ED50	9.572	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148405: Binding affinity to human FXR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0020	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148405: Binding affinity to human FXR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0096	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
sodium arsenite	affects reaction, increases reaction, decreases expression, affects localization, increases expression (+1 more)	3
cobaltous chloride	increases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
K 7174	increases expression	1
pateamine A	affects localization	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases methylation	1
LDN 193189	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3859086	Binding	Binding affinity to FXR1 (unknown origin) at 200 uM by DSF assay	Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. — J Med Chem

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2E2	SEES3-1V human FXR1, clone1	Embryonic stem cell	Male
CVCL_A2E3	SEES3-1V human FXR1, clone2	Embryonic stem cell	Male
CVCL_A2E4	SEES3-1V human FXR1, clone3	Embryonic stem cell	Male
CVCL_B1SF	Abcam HeLa FXR1 KO	Cancer cell line	Female
CVCL_F1M1	HyCyte A-549 KO-hFXR1	Cancer cell line	Male
CVCL_SP06	HAP1 FXR1 (-) 1	Cancer cell line	Male
CVCL_XN99	HAP1 FXR1 (-) 2	Cancer cell line	Male
CVCL_XP00	HAP1 FXR1 (-) 3	Cancer cell line	Male
CVCL_XP01	HAP1 FXR1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00508066	PHASE4	COMPLETED	Continuous Local Infusion of Anesthetic at the Incisional Site for Scoliosis Surgery
NCT00510575	PHASE4	COMPLETED	Surgical Outcomes Using Variable Rod Diameters in the Treatment of Idiopathic Scoliosis
NCT00768313	PHASE4	WITHDRAWN	Phase IV Comparing Rods of Yield Strengths to Correct Adolescent Idiopathic Scoliosis.
NCT00880607	PHASE4	COMPLETED	Intrathecal Morphine Versus Epidural Extended Release Morphine for Pediatric Patients Undergoing Spinal Fusion
NCT00958581	PHASE4	COMPLETED	Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
NCT01852747	PHASE4	TERMINATED	Comparison of Actifuse ABX and Local Bone in Spinal Surgery
NCT02464813	PHASE4	COMPLETED	Effect of Pregabalin on Immediate Post-operative and Longterm Pain
NCT02465099	PHASE4	TERMINATED	Posterior Spinal Fusion With Two Energy Dissection Techniques
NCT06540885	PHASE4	RECRUITING	A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
NCT06616220	PHASE4	COMPLETED	Dexamethasone for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06789016	PHASE4	COMPLETED	Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
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
NCT00323752	PHASE3	COMPLETED	Recombinant Human Erythropoietin Compared to Autologous Pre-Donation Prior to Scoliosis Surgery in Children.
NCT00684112	PHASE3	COMPLETED	Analgesic Effects of Gabapentin After Scoliosis Surgery in Children
NCT00737997	PHASE3	COMPLETED	Effect of Early Morphine Administration on the Development of Acute Opioid Tolerance During Pediatric Scoliosis Surgery
NCT01103115	PHASE3	COMPLETED	Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS)
NCT01108211	PHASE3	COMPLETED	Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS)
NCT01205256	PHASE3	COMPLETED	IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction
NCT02558010	PHASE3	COMPLETED	Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients
NCT03537612	PHASE3	TERMINATED	Sensorial and Physiological Mechanism-based Assessments of Perioperative Pain
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
NCT00273598	PHASE2	COMPLETED	Comparing Two Instrumentation Systems for the Treatment of Adolescent Scoliosis
NCT01148888	PHASE2	COMPLETED	The Effect of Magnesium Sulfate on Motor and Somatosensory Evoked Potentials in Children Undergoing Scoliosis Surgery
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00154505	PHASE1	COMPLETED	Effects of Lateral Trunk Support on Spinal Alignment in Spinal Cord Injured Persons
NCT00155545	PHASE1	COMPLETED	Influence of Leg Length Discrepancy on the Spinal Shape and Biomechanics in Functional and Idiopathic Scoliosis Patients
NCT00671931	PHASE1	COMPLETED	Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine
NCT01677650	PHASE1	WITHDRAWN	Pharmacogenomics of Methadone in Spine Fusion Surgery
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
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