FLRT2

Summary

FLRT2 (fibronectin leucine rich transmembrane protein 2, HGNC:3761) is a protein-coding gene on chromosome 14q31.3, encoding Leucine-rich repeat transmembrane protein FLRT2 (O43155). Functions in cell-cell adhesion, cell migration and axon guidance.

This gene encodes a member of the fibronectin leucine rich transmembrane (FLRT) family of cell adhesion molecules, which regulate early embryonic vascular and neural development. The encoded type I transmembrane protein has an extracellular region consisting of an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, followed by a transmembrane domain and a short C-terminal cytoplasmic tail domain. It functions as both a homophilic cell adhesion molecule and a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. Proteolytic removal of the extracellular region controls the migration of neurons in the developing cortex. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23768 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 95 total — 1 pathogenic
• MANE Select transcript: NM_013231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3761
Approved symbol	FLRT2
Name	fibronectin leucine rich transmembrane protein 2
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185070
Ensembl biotype	protein_coding
OMIM	604807
Entrez	23768

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000330753, ENST00000553627, ENST00000553650, ENST00000554746, ENST00000555398, ENST00000556335, ENST00000557419, ENST00000682132, ENST00000683129, ENST00000684303, ENST00000684438, ENST00000892892, ENST00000892893, ENST00000892894, ENST00000956277, ENST00000956278

RefSeq mRNA: 5 — MANE Select: NM_013231 NM_001346143, NM_001346144, NM_001346145, NM_001346146, NM_013231

CCDS: CCDS9877

Canonical transcript exons

ENST00000330753 — 2 exons

Exon	Start	End
ENSE00001323422	85621139	85654428
ENSE00001405670	85530144	85530534

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5259 / max 752.9189, expressed in 1321 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140901	13.1194	1101
140906	2.8396	860
140902	1.8958	559
140900	1.8343	762
140907	1.1793	708
140898	0.5237	257
140921	0.4947	240
140920	0.4855	277
140908	0.3919	176
140924	0.2044	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.23	gold quality
parietal pleura	UBERON:0002400	98.24	gold quality
middle temporal gyrus	UBERON:0002771	98.02	gold quality
pigmented layer of retina	UBERON:0001782	97.73	gold quality
dorsal root ganglion	UBERON:0000044	97.64	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.31	gold quality
trigeminal ganglion	UBERON:0001675	97.26	gold quality
body of pancreas	UBERON:0001150	97.10	gold quality
tibia	UBERON:0000979	96.77	gold quality
choroid plexus epithelium	UBERON:0003911	96.27	gold quality
stromal cell of endometrium	CL:0002255	95.95	gold quality
hair follicle	UBERON:0002073	95.81	gold quality
superficial temporal artery	UBERON:0001614	95.73	gold quality
pleura	UBERON:0000977	95.57	gold quality
cortical plate	UBERON:0005343	95.57	gold quality
endothelial cell	CL:0000115	95.38	gold quality
orbitofrontal cortex	UBERON:0004167	94.98	gold quality
left ovary	UBERON:0002119	94.84	gold quality
ovary	UBERON:0000992	94.41	gold quality
adrenal tissue	UBERON:0018303	94.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.35	gold quality
tibial nerve	UBERON:0001323	94.21	gold quality
parietal lobe	UBERON:0001872	94.04	gold quality
postcentral gyrus	UBERON:0002581	93.94	gold quality
superior frontal gyrus	UBERON:0002661	93.92	gold quality
pancreas	UBERON:0001264	93.86	gold quality
vena cava	UBERON:0004087	93.64	gold quality
entorhinal cortex	UBERON:0002728	93.44	gold quality
skin of hip	UBERON:0001554	93.42	gold quality
right ovary	UBERON:0002118	93.19	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1882.74
E-GEOD-83139	yes	1189.27
E-GEOD-81547	yes	972.98
E-MTAB-8530	yes	397.12
E-HCAD-35	yes	96.38
E-GEOD-135922	yes	47.06
E-HCAD-10	yes	45.46
E-MTAB-5061	yes	27.09
E-ANND-3	yes	15.48
E-ENAD-27	yes	7.17
E-MTAB-9067	yes	6.21

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• The membrane protein, FLRT2, was identified as a novel autoantigen in systemic lupus erythematosus patients. (PMID:22747982)
• PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe Obstructive sleep apnea in Asian populations (PMID:24732660)
• OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci (PMID:26890304)
• Taken together, these results provide insights into the role of FLRT2 as a novel tumor suppressor in the breast, which is inactivated by hypermethylation during tumor development. (PMID:28325946)
• FLRT2 suppresses bladder cancer progression through inducing ferroptosis. (PMID:37480224)
• FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway. (PMID:38587072)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	flrt2	ENSDARG00000079355
danio_rerio	FLRT2	ENSDARG00000097299
mus_musculus	Flrt2	ENSMUSG00000047414
rattus_norvegicus	Flrt2	ENSRNOG00000003732

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), LRRC19 (ENSG00000184434), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Leucine-rich repeat transmembrane protein FLRT2 — O43155 (reviewed: O43155)

Alternative names: Fibronectin-like domain-containing leucine-rich transmembrane protein 2

All UniProt accessions (2): O43155, A0A804HKH2

UniProt curated annotations — full annotation on UniProt →

Function. Functions in cell-cell adhesion, cell migration and axon guidance. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells. May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D. Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members. Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis.

Subunit / interactions. Self-associates (via leucine-rich repeats), giving rise to homooligomers. Interacts with FGFR1. Interacts with FGFR2. Interacts (via extracellular domain) with ADGRL1/LPHN1. Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity. Interacts (via extracellular domain) with FN1.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Cell junction. Focal adhesion. Secreted. Extracellular space. Extracellular matrix. Microsome membrane. Synapse. Synaptosome.

Tissue specificity. Expressed in pancreas, skeletal muscle, brain, and heart.

Post-translational modifications. N-glycosylated. Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.

RefSeq proteins (5): NP_001333072, NP_001333073, NP_001333074, NP_001333075, NP_037363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050333	SLRP	Family

Pfam: PF01463, PF13855

UniProt features (29 total): repeat 10, glycosylation site 4, disulfide bond 4, domain 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43155-F1	75.10	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.

Disulfide bonds (4): 36–42, 40–49, 314–339, 316–360

Glycosylation sites (4): 202, 298, 433, 521

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5654687	Downstream signaling of activated FGFR1

MSigDB gene sets: 252 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, AAGCAAT_MIR137, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, GOBP_SYNAPSE_ASSEMBLY, NKX25_02, REACTOME_SIGNALING_BY_FGFR, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CTATGCA_MIR153, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (9): heart morphogenesis (GO:0003007), axon guidance (GO:0007411), fibroblast growth factor receptor signaling pathway (GO:0008543), positive regulation of synapse assembly (GO:0051965), cell adhesion involved in heart morphogenesis (GO:0061343), basement membrane organization (GO:0071711), regulation of neuron migration (GO:2001222), cell adhesion (GO:0007155), negative chemotaxis (GO:0050919)

GO Molecular Function (4): fibroblast growth factor receptor binding (GO:0005104), protein-macromolecule adaptor activity (GO:0030674), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (17): obsolete extracellular space (GO:0005615), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), extracellular matrix (GO:0031012), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), postsynaptic membrane (GO:0045211), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cell junction (GO:0030054), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by FGFR1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synaptic membrane	2
cell junction	2
heart development	1
animal organ morphogenesis	1
axonogenesis	1
neuron projection guidance	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
heart morphogenesis	1
cell adhesion	1
extracellular matrix organization	1
neuron migration	1
regulation of cell migration	1
cellular process	1
chemotaxis	1
growth factor receptor binding	1
protein binding	1
molecular adaptor activity	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
anchoring junction	1
cell-substrate junction	1
external encapsulating structure	1
presynapse	1
plasma membrane bounded cell projection	1
postsynapse	1
extracellular vesicle	1
synapse	1
cytoplasm	1

Protein interactions and networks

STRING

1346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLRT2	UNC5D	Q6UXZ4	827
FLRT2	FN1	P02751	804
FLRT2	UNC5B	Q8IZJ1	685
FLRT2	FGFR2	P18443	647
FLRT2	NID1	P14543	595
FLRT2	NTN1	O95631	548
FLRT2	ADGRL1	O94910	548
FLRT2	MACROD2	A1Z1Q3	547
FLRT2	UNC5A	Q6ZN44	493
FLRT2	ERV3-1	Q14264	492
FLRT2	ERVFRD-1	P60508	491
FLRT2	ADGRL3	Q9HAR2	470
FLRT2	ROBO4	Q8WZ75	466
FLRT2	ADGRL2	O95490	455
FLRT2	PROX2	Q3B8N5	430

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FLRT2	VDAC1	psi-mi:“MI:0915”(physical association)	0.400
flrt3	FLRT2	psi-mi:“MI:0915”(physical association)	0.400
FLRT2		psi-mi:“MI:0915”(physical association)	0.400
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
FLRT2	FLRT2	psi-mi:“MI:2364”(proximity)	0.270
FLRT1	FLRT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (24): FLRT2 (Synthetic Lethality), VDAC1 (Proximity Label-MS), FLRT2 (Reconstituted Complex), UNC5D (Reconstituted Complex), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS), FLRT2 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, A4IIW9, B0BLW3, B1H134, B1H234, B4F7C5, D3ZAL8, D3ZTV3, D4A7P2, E5DHB5, F1NUK7, F7D3V9, O43155, O43300, O94898, P58681, Q32Q07, Q3SXY7, Q3URE9, Q504C1, Q50L44, Q52KR2, Q5R482, Q5R6T0, Q5RDJ4, Q61809, Q66HV9, Q6RKD8, Q6UXK5, Q70AK3, Q7L985, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q86VH4, Q86VH5, Q8BGA3, Q8BGT1, Q8BLU0

Diamond homologs: B1H134, B1H234, D3ZTV3, F1NUK7, G5EFX6, G5EG78, O43155, O88280, P19879, P20774, P24014, P58874, P79119, P83286, Q5R6T0, Q5RAC4, Q5RBL2, Q62000, Q6PEZ8, Q6RKD8, Q70AK3, Q810C1, Q8BGT1, Q8BLU0, Q8MJF1, Q96PX8, Q9DE65, Q9NR97, Q9NZU0, Q9NZU1, Q9UBM4, Q9W6H0, A8WGA3, D4ABX8, O42235, O55226, O60938, O75093, O88279, O94769

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997827	Single allele	Pathogenic

SpliceAI

2520 predictions. Top by Δscore:

Variant	Effect	Δscore
14:85540534:T:G	acceptor_gain	1.0000
14:85612737:G:GG	donor_gain	0.9900
14:85621137:A:AG	acceptor_gain	0.9900
14:85621138:G:GG	acceptor_gain	0.9900
14:85530542:GGGC:G	donor_gain	0.9800
14:85540535:A:AG	acceptor_gain	0.9800
14:85540536:G:GG	acceptor_gain	0.9800
14:85556585:TTCA:T	donor_gain	0.9800
14:85612736:A:AG	donor_gain	0.9800
14:85621131:T:A	acceptor_gain	0.9800
14:85621133:CAACA:C	acceptor_gain	0.9800
14:85621134:A:AG	acceptor_gain	0.9800
14:85621134:AACAG:A	acceptor_gain	0.9800
14:85621135:ACAGA:A	acceptor_gain	0.9800
14:85621136:CA:C	acceptor_loss	0.9800
14:85621137:AG:A	acceptor_loss	0.9800
14:85530530:GTCAG:G	donor_loss	0.9700
14:85530533:AGGTA:A	donor_loss	0.9700
14:85530534:G:GC	donor_loss	0.9700
14:85530535:G:GA	donor_loss	0.9700
14:85530536:T:G	donor_loss	0.9700
14:85531223:G:GG	donor_gain	0.9700
14:85578011:A:T	donor_gain	0.9700
14:85584709:GGTTC:G	donor_gain	0.9700
14:85604212:T:G	acceptor_gain	0.9700
14:85612792:GCT:G	donor_gain	0.9700
14:85613926:A:T	donor_gain	0.9700
14:85619932:A:T	donor_gain	0.9700
14:85621136:CAGA:C	acceptor_gain	0.9700
14:85621138:GA:G	acceptor_gain	0.9700

AlphaMissense

4344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:85621659:T:A	C49S	1.000
14:85621659:T:C	C49R	1.000
14:85621660:G:A	C49Y	1.000
14:85621660:G:C	C49S	1.000
14:85621661:T:G	C49W	1.000
14:85621717:T:C	L68P	1.000
14:85621723:T:C	L70P	1.000
14:85621733:C:A	N73K	1.000
14:85621733:C:G	N73K	1.000
14:85621792:T:A	V93D	1.000
14:85621798:T:C	L95P	1.000
14:85621808:C:A	N98K	1.000
14:85621808:C:G	N98K	1.000
14:85621855:T:C	L114P	1.000
14:85621869:A:C	N119H	1.000
14:85621869:A:T	N119Y	1.000
14:85621870:A:T	N119I	1.000
14:85621871:C:A	N119K	1.000
14:85621871:C:G	N119K	1.000
14:85621927:T:C	L138P	1.000
14:85621933:T:C	L140P	1.000
14:85621941:A:T	N143Y	1.000
14:85621942:A:T	N143I	1.000
14:85621943:C:A	N143K	1.000
14:85621943:C:G	N143K	1.000
14:85621948:T:A	I145K	1.000
14:85621978:T:C	F155S	1.000
14:85622019:A:G	N169D	1.000
14:85622021:T:A	N169K	1.000
14:85622021:T:G	N169K	1.000

dbSNP variants (sampled 300 via entrez): RS1000050082 (14:85651077 T>A,C), RS1000065146 (14:85548327 C>G), RS1000070991 (14:85635204 A>G), RS1000109268 (14:85562875 G>GA), RS1000130595 (14:85626967 T>A), RS1000164845 (14:85593463 G>T), RS1000169563 (14:85651259 G>A,T), RS1000221529 (14:85638865 A>C,G), RS1000231068 (14:85610339 T>C), RS1000240436 (14:85531701 C>A), RS1000262416 (14:85610192 T>A), RS1000272575 (14:85571103 T>C), RS1000285826 (14:85583707 T>C), RS1000314587 (14:85531379 G>A), RS1000330858 (14:85577711 C>T)

Disease associations

OMIM: gene MIM:604807 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST001444_12	Pulmonary function decline	7.000000e-06
GCST001969_3	Heart rate	3.000000e-13
GCST001973_9	Menarche (age at onset)	3.000000e-07
GCST002040_10	Blood trace element (Zn levels)	3.000000e-06
GCST002988_4	Ischemic stroke	9.000000e-07
GCST003818_32	Resting heart rate	7.000000e-29
GCST003831_33	Asthma	4.000000e-06
GCST004946_164	Schizophrenia	5.000000e-08
GCST005789_26	Resting heart rate	3.000000e-14
GCST006436_10	Triglyceride levels	5.000000e-08
GCST006585_1381	Blood protein levels	5.000000e-16
GCST007576_170	Chronotype	2.000000e-09
GCST008478_41	Neurological blood protein biomarker levels	3.000000e-17
GCST009723_76	Vertical cup-disc ratio (adjusted for vertical disc diameter)	1.000000e-08
GCST009724_59	Vertical cup-disc ratio (multi-trait analysis)	3.000000e-12
GCST010320_22	PR interval	3.000000e-10
GCST010321_41	PR interval	2.000000e-10
GCST010796_5207	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_5208	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_5209	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_5210	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5211	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5212	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5213	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5214	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_5215	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5216	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_5217	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST012047_8	Fasting glucose	6.000000e-07
GCST012047_9	Fasting glucose	6.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004703	age at menarche
EFO:0004530	triglyceride measurement
EFO:0008328	chronotype measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression, affects cotreatment	7
bisphenol A	affects methylation, affects cotreatment, increases methylation, increases expression	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	3
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	3
Aflatoxin B1	decreases methylation, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Cadmium Chloride	decreases expression	2
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	increases expression	1
lead acetate	increases expression	1
titanium dioxide	increases expression	1
terbufos	increases methylation	1
arsenite	decreases expression	1
nickel chloride	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
caffeic acid	decreases expression, increases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	increases reaction, affects expression	1
torcetrapib	increases expression	1

Clinical trials (associated diseases)

197 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
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
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
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)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders