FXR2

Summary

FXR2 (FMR1 autosomal homolog 2, HGNC:4024) is a protein-coding gene on chromosome 17p13.1, encoding RNA-binding protein FXR2 (P51116). mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis.

The protein encoded by this gene is a RNA binding protein containing two KH domains and one RCG box, which is similar to FMRP and FXR1. It associates with polyribosomes, predominantly with 60S large ribosomal subunits. This encoded protein may self-associate or interact with FMRP and FXR1. It may have a role in the development of fragile X cognitive disability syndrome.

Source: NCBI Gene 9513 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 99 total
• Druggable target: yes
• MANE Select transcript: NM_004860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4024
Approved symbol	FXR2
Name	FMR1 autosomal homolog 2
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000129245
Ensembl biotype	protein_coding
OMIM	605339
Entrez	9513

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 retained_intron, 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000250113, ENST00000571079, ENST00000571597, ENST00000573057, ENST00000573957, ENST00000574490, ENST00000576693, ENST00000704984

RefSeq mRNA: 1 — MANE Select: NM_004860 NM_004860

CCDS: CCDS45604

Canonical transcript exons

ENST00000250113 — 17 exons

Exon	Start	End
ENSE00000887341	7592254	7592354
ENSE00000887343	7592504	7592599
ENSE00000887348	7592984	7593181
ENSE00000887353	7593918	7594004
ENSE00000887354	7594238	7594347
ENSE00000887356	7594679	7594757
ENSE00000887360	7601409	7601525
ENSE00000887362	7602909	7603002
ENSE00000887366	7604009	7604080
ENSE00000949182	7593403	7593625
ENSE00001147578	7605645	7605738
ENSE00001147587	7606097	7606149
ENSE00001147605	7614452	7614897
ENSE00001293858	7592694	7592894
ENSE00001309181	7591230	7591925
ENSE00003656017	7595824	7595994
ENSE00003677448	7603757	7603905

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1868 / max 86.1217, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164265	8.2694	1766
164264	1.0119	626
164263	0.9055	524

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.36	gold quality
gastrocnemius	UBERON:0001388	96.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.52	gold quality
muscle of leg	UBERON:0001383	96.20	gold quality
superior vestibular nucleus	UBERON:0007227	96.13	gold quality
heart left ventricle	UBERON:0002084	95.91	gold quality
cardiac ventricle	UBERON:0002082	95.80	gold quality
pons	UBERON:0000988	95.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.51	gold quality
cerebellar hemisphere	UBERON:0002245	95.50	gold quality
cerebellar cortex	UBERON:0002129	95.42	gold quality
inferior vagus X ganglion	UBERON:0005363	95.41	gold quality
muscle organ	UBERON:0001630	95.21	gold quality
skeletal muscle organ	UBERON:0014892	95.21	gold quality
right atrium auricular region	UBERON:0006631	95.18	gold quality
ventral tegmental area	UBERON:0002691	95.17	gold quality
dorsal root ganglion	UBERON:0000044	95.16	gold quality
body of tongue	UBERON:0011876	95.01	gold quality
cardiac atrium	UBERON:0002081	94.98	gold quality
cerebellum	UBERON:0002037	94.88	gold quality
trigeminal ganglion	UBERON:0001675	94.78	gold quality
prefrontal cortex	UBERON:0000451	94.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.73	gold quality
right frontal lobe	UBERON:0002810	94.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.63	gold quality
heart	UBERON:0000948	94.59	gold quality
medulla oblongata	UBERON:0001896	94.59	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.58	gold quality
diaphragm	UBERON:0001103	94.55	gold quality
ganglionic eminence	UBERON:0004023	94.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.37
E-MTAB-7303	no	96.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFYA, NFYB, NFYC, NRF1, SP1

miRNA regulators (miRDB)

107 targeting FXR2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466

Literature-anchored findings (GeneRIF, showing 8)

• 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)
• 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)
• 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)
• 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)
• LLPS of FXR proteins drives replication organelle clustering for beta-coronaviral proliferation. (PMID:38587486)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fxr2	ENSDARG00000016260
mus_musculus	Fxr2	ENSMUSG00000018765
rattus_norvegicus	Fxr2	ENSRNOG00000011876
drosophila_melanogaster	Fmr1	FBGN0028734

Paralogs (2): FMR1 (ENSG00000102081), FXR1 (ENSG00000114416)

Protein

Protein identifiers

RNA-binding protein FXR2 — P51116 (reviewed: P51116)

Alternative names: FMR1 autosomal homolog 2

All UniProt accessions (3): P51116, A0A994J7P9, I3L1Z2

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 adult hippocampal neurogenesis. 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: mRNAs storage into membraneless compartments regulates their translation and/or stability. Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus.

Subunit / interactions. Interacts with FMR1. Interacts with FXR1. Interacts with TDRD3. Interacts with HABP4. Interacts with CYFIP2 but not with CYFIP1. (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-FXR2 complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes.

Subcellular location. Cytoplasm. Cytoplasmic ribonucleoprotein granule. 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).

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.

Similarity. Belongs to the FMR1 family.

RefSeq proteins (1): NP_004851* (*=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
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR040148	FMR1	Family
IPR040472	FMRP_KH0	Domain
IPR041560	Tudor_FRM1	Domain
IPR047420	Tudor_Agenet_FXR2_rpt2	Domain
IPR047421	Tudor_Agenet_FXR2_rpt1	Domain
IPR047422	KH_I_FXR2_rpt1	Domain
IPR047424	KH_I_FXR2_rpt2	Domain

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

UniProt features (37 total): modified residue 12, strand 9, compositionally biased region 5, domain 4, sequence variant 2, helix 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3H8Z	X-RAY DIFFRACTION	1.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51116-F1	69.09	0.42

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 (12): 78, 192, 410, 411, 450, 453, 533, 566, 580, 598, 601, 603

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): GOBP_DENTATE_GYRUS_DEVELOPMENT, GGTGTGT_MIR329, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, SP3_Q3, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, AP2_Q3, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_TRANSLATION

GO Biological Process (9): dentate gyrus development (GO:0021542), regulation of mRNA stability (GO:0043488), positive regulation of translation (GO:0045727), positive regulation of long-term neuronal synaptic plasticity (GO:0048170), animal organ development (GO:0048513), mRNA transport (GO:0051028), mRNA destabilization (GO:0061157), regulation of translation at presynapse, modulating synaptic transmission (GO:0099577), regulation of translation (GO:0006417)

GO Molecular Function (9): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), translation regulator activity (GO:0045182), protein heterodimerization activity (GO:0046982), nucleic acid binding (GO:0003676), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), neuron projection (GO:0043005), presynapse (GO:0098793), postsynapse (GO:0098794), cytoplasmic ribonucleoprotein granule (GO:0036464), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
translation	3
anatomical structure development	2
regulation of translation	2
protein dimerization activity	2
binding	2
cytoplasm	2
synapse	2
hippocampus development	1
regulation of RNA stability	1
regulation of mRNA catabolic process	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
RNA transport	1
negative regulation of gene expression	1
regulation of mRNA stability	1
RNA destabilization	1
positive regulation of mRNA catabolic process	1
chemical synaptic transmission	1
presynapse	1
presynaptic modulation of chemical synaptic transmission	1
regulation of translation at synapse, modulating synaptic transmission	1
regulation of translation at presynapse	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleic acid binding	1
mRNA binding	1
protein binding	1
identical protein binding	1
molecular_function	1
RNA binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1
plasma membrane bounded cell projection	1
ribonucleoprotein granule	1
cell junction	1

Protein interactions and networks

STRING

2454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FXR2	CYFIP1	Q7L576	997
FXR2	CYFIP2	Q96F07	994
FXR2	PUF60	Q9UHX1	958
FXR2	FXR1	P51114	956
FXR2	HNRNPK	P61978	954
FXR2	NUFIP1	Q9UHK0	938
FXR2	AGO2	Q9UKV8	926
FXR2	DICER1	Q9UPY3	900
FXR2	SF3B3	Q15393	895
FXR2	CPEB1	Q9BZB8	882
FXR2	PURA	Q00577	880
FXR2	KCNG1	Q9UIX4	873
FXR2	NUFIP2	Q7Z417	851
FXR2	TDRD3	Q9H7E2	839
FXR2	MAP1B	P46821	824

IntAct

528 interactions, top by confidence:

A	B	Type	Score
PCBD1	FXR2	psi-mi:“MI:0915”(physical association)	0.800
FXR2	PCBD1	psi-mi:“MI:0915”(physical association)	0.800
LCP2	FXR2	psi-mi:“MI:0915”(physical association)	0.780
CDKL3	FXR2	psi-mi:“MI:0915”(physical association)	0.780
FXR2	PRAM1	psi-mi:“MI:0915”(physical association)	0.780
FXR2	AP1M1	psi-mi:“MI:0915”(physical association)	0.780
FXR2	LCP2	psi-mi:“MI:0915”(physical association)	0.780
FXR2	CDKL3	psi-mi:“MI:0915”(physical association)	0.780
PRAM1	FXR2	psi-mi:“MI:0915”(physical association)	0.780
AP1M1	FXR2	psi-mi:“MI:0915”(physical association)	0.780
FXR2	FXR2	psi-mi:“MI:0915”(physical association)	0.760
FXR2	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.740
TBC1D22B	FXR2	psi-mi:“MI:0915”(physical association)	0.740
YES1	FXR2	psi-mi:“MI:0915”(physical association)	0.720
FXR2	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
FXR2	BYSL	psi-mi:“MI:0915”(physical association)	0.720
BYSL	FXR2	psi-mi:“MI:0915”(physical association)	0.720
FXR2	SYT6	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (652): FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), FXR2 (Two-hybrid), POM121 (Two-hybrid)

ESM2 similar proteins: A0JNJ3, A1A5Q0, A6H7G2, D3Z8X7, D3ZND0, F1LM81, O14976, O60308, O70523, P51114, P51116, P70501, P97874, P98175, Q16643, Q2V2M9, Q2VUH7, Q3UHZ5, Q5BJ56, Q5F4B2, Q5FVK6, Q5T0F9, Q5T1M5, Q60902, Q61584, Q62418, Q66HA5, Q68FU8, Q69ZX6, Q6GM14, Q6P1N0, Q6P9Q6, Q7SYB5, Q7ZXQ9, Q80U87, Q80V31, Q8BRN9, Q8CH02, Q8IWZ8, Q8K1A6

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7592253:CCTT:C	donor_gain	1.0000
17:7592353:CA:C	acceptor_gain	1.0000
17:7592355:C:CC	acceptor_gain	1.0000
17:7592453:T:TA	donor_gain	1.0000
17:7592454:C:A	donor_gain	1.0000
17:7592466:G:C	donor_gain	1.0000
17:7592595:ATCTT:A	acceptor_gain	1.0000
17:7592596:TCTT:T	acceptor_loss	1.0000
17:7592597:CTT:C	acceptor_gain	1.0000
17:7592597:CTTC:C	acceptor_loss	1.0000
17:7592598:TT:T	acceptor_gain	1.0000
17:7592598:TTCTG:T	acceptor_loss	1.0000
17:7592599:TC:T	acceptor_loss	1.0000
17:7592600:C:CA	acceptor_loss	1.0000
17:7592600:C:CC	acceptor_gain	1.0000
17:7592601:T:A	acceptor_loss	1.0000
17:7592602:G:C	acceptor_gain	1.0000
17:7592602:G:GC	acceptor_gain	1.0000
17:7592607:G:C	acceptor_gain	1.0000
17:7592607:G:GC	acceptor_gain	1.0000
17:7592687:C:CA	donor_gain	1.0000
17:7592689:CTCA:C	donor_loss	1.0000
17:7592691:CA:C	donor_loss	1.0000
17:7592692:A:C	donor_loss	1.0000
17:7592692:AC:A	donor_gain	1.0000
17:7592693:CC:C	donor_gain	1.0000
17:7592696:AGG:A	donor_gain	1.0000
17:7592723:T:C	donor_gain	1.0000
17:7592729:T:TA	donor_gain	1.0000
17:7592737:T:TA	donor_gain	1.0000

AlphaMissense

4343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7593579:A:G	L385P	1.000
17:7593579:A:T	L385H	1.000
17:7593612:A:G	L374P	1.000
17:7593922:A:G	L368P	1.000
17:7593931:A:G	L365P	1.000
17:7593934:T:G	H364P	1.000
17:7593935:G:C	H364D	1.000
17:7593938:A:C	Y363D	1.000
17:7593938:A:G	Y363H	1.000
17:7593943:A:G	L361P	1.000
17:7593946:A:G	L360S	1.000
17:7593955:G:T	A357D	1.000
17:7593956:C:G	A357P	1.000
17:7593979:C:A	G349V	1.000
17:7593979:C:T	G349D	1.000
17:7593980:C:A	G349C	1.000
17:7593980:C:G	G349R	1.000
17:7593982:A:T	V348D	1.000
17:7593985:A:G	F347S	1.000
17:7593990:G:C	F345L	1.000
17:7593990:G:T	F345L	1.000
17:7593991:A:G	F345S	1.000
17:7593992:A:G	F345L	1.000
17:7594281:A:T	V326D	1.000
17:7594296:G:A	S321F	1.000
17:7594297:A:G	S321P	1.000
17:7594298:T:A	K320N	1.000
17:7594298:T:G	K320N	1.000
17:7594300:T:C	K320E	1.000
17:7594313:C:A	Q315H	1.000

dbSNP variants (sampled 300 via entrez): RS1000001622 (17:7599979 C>A), RS1000153992 (17:7594140 C>A,T), RS1000334464 (17:7602398 T>C), RS1000392088 (17:7596305 C>A,G), RS1000680357 (17:7596551 G>A,C,T), RS1000795052 (17:7601019 T>A,C), RS1000844815 (17:7604564 T>C), RS1000860419 (17:7608181 C>G,T), RS1000897073 (17:7604815 G>A), RS1000959899 (17:7611487 G>A), RS1000978984 (17:7614497 C>A,G,T), RS1001096819 (17:7614285 G>A,C), RS1001115521 (17:7605123 C>G), RS1001133950 (17:7594811 G>A), RS1001142035 (17:7611248 C>T)

Disease associations

OMIM: gene MIM:605339 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001554_1	Sex hormone-binding globulin levels	2.000000e-16
GCST001724_2	IgM levels	2.000000e-07
GCST006414_33	Atrial fibrillation	2.000000e-09
GCST010002_119	Refractive error	3.000000e-22
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST90002393_509	Monocyte count	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004346	neuroimaging measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169136 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9901675	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

ChEMBL bioactivities

9 potent at pChembl≥5 of 9 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.46	EC50	0.35	nM	CHEMBL5267458
9.12	EC50	0.75	nM	CHEMBL3822464
7.08	EC50	84	nM	CHEMBL4862974
7.07	EC50	85	nM	CHEMBL5182534
6.82	EC50	150	nM	CHEMBL4862974
6.72	EC50	191	nM	CHEMBL5182534
6.61	EC50	243	nM	CHEMBL4862974
6.55	EC50	281	nM	CHEMBL4862974
6.41	EC50	389	nM	CHEMBL5182534

PubChem BioAssay actives

9 with measured affinity, of 24 total; 4 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
2-[(1S,4S,5R)-5-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-2-azabicyclo[2.2.1]heptan-2-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid	1932884: Agonist activity at FXR2 in human HepG2 cells	ec50	0.0003	uM
4-[(1R,2R)-2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoic acid	1932884: Agonist activity at FXR2 in human HepG2 cells	ec50	0.0008	uM
6-[2-[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-1,2-oxazol-4-yl]-7-azaspiro[3.5]non-2-en-7-yl]-4-(trifluoromethyl)quinoline-2-carboxylic acid	1892353: Agonist activity at human FXR2 expressed in HEK293 cells coexpressing IBABP	ec50	0.0840	uM
N-[[4-[5-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-hydroxy-N-[3-[4-(2-hydroxypropan-2-yl)phenyl]phenyl]-3-(trifluoromethyl)cyclobutane-1-carboxamide	1892353: Agonist activity at human FXR2 expressed in HEK293 cells coexpressing IBABP	ec50	0.0850	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases activity, increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Aspirin	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5148480	Binding	Agonist activity at human FXR2 expressed in HEK293 cells coexpressing human FGF19 incubated for 24 hrs by ELISA analysis relative to GW2064	Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0216	CMK	Cancer cell line	Male
CVCL_0217	CMK-11-5	Cancer cell line	Male
CVCL_2804	CMK-86	Cancer cell line	Male
CVCL_C8FM	HAP1 FXR2 (-)	Cancer cell line	Male
CVCL_RM24	CMK-6	Cancer cell line	Male

Clinical trials (associated diseases)

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