RGMA

Summary

RGMA (repulsive guidance molecule BMP co-receptor a, HGNC:30308) is a protein-coding gene on chromosome 15q26.1, encoding Repulsive guidance molecule A (Q96B86). Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system.

This gene encodes a member of the repulsive guidance molecule family. The encoded protein is a glycosylphosphatidylinositol-anchored glycoprotein that functions as an axon guidance protein in the developing and adult central nervous system. This protein may also function as a tumor suppressor in some cancers. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 56963 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 90 total
• Druggable target: yes
• MANE Select transcript: NM_020211

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30308
Approved symbol	RGMA
Name	repulsive guidance molecule BMP co-receptor a
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	RGM
Ensembl gene	ENSG00000182175
Ensembl biotype	protein_coding
OMIM	607362
Entrez	56963

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000329082, ENST00000425933, ENST00000542321, ENST00000543599, ENST00000554387, ENST00000555584, ENST00000555598, ENST00000556658, ENST00000556950, ENST00000557301, ENST00000557420, ENST00000557608, ENST00000650169

RefSeq mRNA: 6 — MANE Select: NM_020211 NM_001166283, NM_001166286, NM_001166287, NM_001166288, NM_001166289, NM_020211

CCDS: CCDS45357, CCDS53973, CCDS53974

Canonical transcript exons

ENST00000329082 — 4 exons

Exon	Start	End
ENSE00001532613	93088919	93089211
ENSE00002519404	93035271	93045705
ENSE00003669262	93051993	93052507
ENSE00003672915	93072916	93073031

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.79.

FANTOM5 (CAGE): breadth broad, TPM avg 14.9795 / max 440.1206, expressed in 772 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151661	9.4454	403
151655	4.2076	723
151662	0.4909	208
151660	0.4121	144
151659	0.3170	134
151656	0.0870	46
151657	0.0193	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus	UBERON:0013473	97.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.79	gold quality
gastrocnemius	UBERON:0001388	97.40	gold quality
ventricular zone	UBERON:0003053	96.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.53	gold quality
tibialis anterior	UBERON:0001385	96.40	gold quality
muscle of leg	UBERON:0001383	96.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.09	gold quality
lower esophagus mucosa	UBERON:0035834	95.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.96	gold quality
esophagus	UBERON:0001043	94.84	gold quality
endocervix	UBERON:0000458	93.45	gold quality
mucosa of stomach	UBERON:0001199	93.25	gold quality
left uterine tube	UBERON:0001303	93.19	gold quality
hypothalamus	UBERON:0001898	93.06	gold quality
apex of heart	UBERON:0002098	92.78	gold quality
esophagus mucosa	UBERON:0002469	92.66	gold quality
body of uterus	UBERON:0009853	92.61	gold quality
right frontal lobe	UBERON:0002810	92.32	gold quality
substantia nigra	UBERON:0002038	92.30	gold quality
anterior cingulate cortex	UBERON:0009835	92.23	gold quality
ectocervix	UBERON:0012249	92.14	gold quality
nucleus accumbens	UBERON:0001882	92.01	gold quality
midbrain	UBERON:0001891	91.75	gold quality
caudate nucleus	UBERON:0001873	91.68	gold quality
skeletal muscle tissue	UBERON:0001134	91.57	gold quality
lateral globus pallidus	UBERON:0002476	91.44	gold quality
tibial nerve	UBERON:0001323	91.42	gold quality
ganglionic eminence	UBERON:0004023	91.36	gold quality
uterine cervix	UBERON:0000002	91.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.83
E-MTAB-6911	no	211.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HAMP	Activation

miRNA regulators (miRDB)

108 targeting RGMA, 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-5692A	100.00	74.40	6850
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 19)

• Following central nervous system injury, RGM, a novel, potent axonal growth inhibitor, is present in axonal growth impediments: the mature myelin, choroid plexus, and components of the developing scar. (PMID:16216939)
• RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and increased utilization of ActRIIA leads to generation of an enhanced BMP signal (PMID:17472960)
• detected a homozygous deletion of chromosomal region 15q26.2 in the cell line HDLM2 encompasing RGMA and CHD2 (PMID:17606441)
• this study, we show that Unc5B, a member of the netrin receptor family, interacts with neogenin as a coreceptor for RGMa. (PMID:19273616)
• Frequent inactivation of axon guidance molecule RGMA in human colon cancer through genetic and epigenetic mechanisms. (PMID:19303019)
• The full-length signal peptides of RGMa is functional and furthermore that the C-domains are sufficient and essential for ER targeting, whereas the N-domains are dispensable. Thus, the N-domains are available for additional functions. (PMID:21183991)
• RGM-A is a unique endogenous inhibitor of leukocyte chemotaxis that limits inflammatory leukocyte traffic (PMID:21467223)
• Reduced expression of RGMA in breast cancer was associated with breast cancer. (PMID:21617229)
• The expression of RGMA, RGMB and RGMC was evident in most examined prostate cancer cell lines, and also in the prostate cancer tissues (PMID:22076499)
• RGMa expression and promoter methylation status are closely related to colorectal cancer genesis and progression. (PMID:22367090)
• identification of neogenin-binding site on the repulsive guidance molecule A (PMID:22396795)
• Thus, we conclude that RGMa inhibits angiogenesis in vitro and in vivo suggesting that its manipulation would be an efficient therapeutic strategy for pro-angiogenic conditions. (PMID:26721439)
• Dysregulation of RGMa plays an important role in the pathology of Parkinson’s disease. (PMID:28842419)
• a regulatory variant of RGMA is associated with opioid dependence in European Americans (PMID:29478698)
• RGMA is regulated by the HIF1A/miR-210 axis and inhibits oral squamous cell carcinoma. (PMID:30798120)
• MicroRNA-4472 Promotes Tumor Proliferation and Aggressiveness in Breast Cancer by Targeting RGMA and Inducing EMT. (PMID:31899158)
• Repulsive Guidance Molecule-a and Central Nervous System Diseases. (PMID:33997000)
• Decreased DNA Methylation of RGMA is Associated with Intracranial Hypertension After Severe Traumatic Brain Injury: An Exploratory Epigenome-Wide Association Study. (PMID:35028889)
• Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis. (PMID:38762192)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgma	ENSDARG00000012248
mus_musculus	Rgma	ENSMUSG00000070509
rattus_norvegicus	Rgma	ENSRNOG00000012874
caenorhabditis_elegans	drag-1	WBGENE00022154

Paralogs (2): HJV (ENSG00000168509), RGMB (ENSG00000174136)

Protein

Protein identifiers

Repulsive guidance molecule A — Q96B86 (reviewed: Q96B86)

Alternative names: RGM domain family member A

All UniProt accessions (7): Q96B86, A0A0A0MTQ4, A0A0G2JL92, F5H7G2, G3V3Z3, G3V4C2, G3V545

UniProt curated annotations — full annotation on UniProt →

Function. Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.

Subunit / interactions. Interacts with NEO1, BMP2 and BMP4.

Subcellular location. Cell membrane.

Post-translational modifications. Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.

Similarity. Belongs to the repulsive guidance molecule (RGM) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96B86-1	1	yes
Q96B86-3	2
Q96B86-4	3

RefSeq proteins (6): NP_001159755, NP_001159758, NP_001159759, NP_001159760, NP_001159761, NP_064596* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009496	RGM_C	Domain
IPR010536	RGM_N	Domain
IPR040287	RGM	Family

Pfam: PF06534, PF06535

UniProt features (24 total): glycosylation site 3, turn 3, propeptide 2, disulfide bond 2, splice variant 2, sequence variant 2, sequence conflict 2, helix 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6Z3G	X-RAY DIFFRACTION	2.78
4UHY	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B86-F1	79.42	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 168–169 (cleavage; by autolysis)

Post-translational modifications (1): 424

Disulfide bonds (2): 145–226, 163–315

Glycosylation sites (3): 389, 114, 159

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-373752	Netrin-1 signaling

MSigDB gene sets: 179 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, HNF3ALPHA_Q6, AREB6_03, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, GOBP_NEURAL_TUBE_DEVELOPMENT, AP2_Q3, GGGTGGRR_PAX4_03, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM

GO Biological Process (13): neural tube closure (GO:0001843), membrane protein ectodomain proteolysis (GO:0006509), positive regulation of neuron projection development (GO:0010976), BMP signaling pathway (GO:0030509), regulation of BMP signaling pathway (GO:0030510), neuron projection development (GO:0031175), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of collateral sprouting (GO:0048671), negative regulation of axon regeneration (GO:0048681), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), positive regulation of macromolecule metabolic process (GO:0010604), negative regulation of neuron projection development (GO:0010977), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (4): coreceptor activity (GO:0015026), transferrin receptor binding (GO:1990459), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), cell surface (GO:0009986), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of neuron projection development	2
neuron projection development	2
membrane	2
primary neural tube formation	1
tube closure	1
membrane protein proteolysis	1
positive regulation of cell projection organization	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
BMP signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to growth factor stimulus	1
neuron development	1
plasma membrane bounded cell projection organization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
negative regulation of cell growth	1
negative regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
negative regulation of axonogenesis	1
axon regeneration	1
negative regulation of response to external stimulus	1
regulation of axon regeneration	1
negative regulation of neuron projection regeneration	1
negative regulation of response to wounding	1
membrane protein ectodomain proteolysis	1
positive regulation of protein catabolic process	1
positive regulation of proteolysis	1
regulation of membrane protein ectodomain proteolysis	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1
negative regulation of cell projection organization	1
regulation of metabolic process	1
primary metabolic process	1
signaling receptor activity	1
signaling receptor binding	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGMA	NEO1	Q92859	999
RGMA	DRGX	A6NNA5	861
RGMA	UNC5B	Q8IZJ1	649
RGMA	CSF2	P04141	644
RGMA	BMP4	P12644	635
RGMA	NTN1	O95631	612
RGMA	MCTP2	Q6DN12	580
RGMA	EPHA4	P54764	496
RGMA	ACVR2A	P27037	494
RGMA	CNIH3	Q8TBE1	480
RGMA	PDLIM4	P50479	477
RGMA	LRIG2	O94898	441
RGMA	KCNG2	Q9UJ96	439
RGMA	OMG	P23515	433
RGMA	ITGAX	P20702	433

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RGMA	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
RGMA	BDP1	psi-mi:“MI:0914”(association)	0.350
RGMA	TERF2IP	psi-mi:“MI:0915”(physical association)	0.000
PPP1R16A	RGMA	psi-mi:“MI:0915”(physical association)	0.000
SGSM2	RGMA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): TCEB2 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), TXNIP (Affinity Capture-MS), HIPK2 (Affinity Capture-MS), PPHLN1 (Affinity Capture-MS), SAMD4B (Affinity Capture-MS), BDP1 (Affinity Capture-MS), CLK4 (Affinity Capture-MS), ANO3 (Affinity Capture-MS), NBEAL1 (Affinity Capture-MS), SPICE1 (Affinity Capture-MS), RGMA (Affinity Capture-MS), RGMA (Two-hybrid), RGMA (Two-hybrid), RGMA (Two-hybrid)

ESM2 similar proteins: A1XQX1, A1XQX3, A1XQY0, A8WGA3, C6K2K4, D0PRN2, D0PRN4, D4A1J9, E9PUN2, O13097, O42596, O73612, O73874, P0DI97, P52795, P52796, P58400, P58401, P98172, Q01974, Q0PMD2, Q17QD6, Q28142, Q28143, Q460M5, Q63373, Q63376, Q6NW40, Q6PCX7, Q6PFE7, Q7TQ33, Q80TG9, Q8BNJ6, Q8BXA0, Q8C985, Q8IYR6, Q8NC67, Q91590, Q96B86, Q96NI6

Diamond homologs: G5EDE5, Q6NW40, Q6PCX7, Q6ZVN8, Q7TQ32, Q7TQ33, Q8JG54, Q8N7M5, Q96B86, Q9N0A6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RGMA	“down-regulates activity”	NEO1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1219 predictions. Top by Δscore:

Variant	Effect	Δscore
15:93045701:GTGAG:G	acceptor_gain	0.9900
15:93045702:TGAG:T	acceptor_gain	0.9900
15:93045703:GAG:G	acceptor_gain	0.9900
15:93045704:AG:A	acceptor_gain	0.9900
15:93045705:GC:G	acceptor_loss	0.9900
15:93045706:C:CA	acceptor_loss	0.9900
15:93045706:C:CC	acceptor_gain	0.9900
15:93045707:T:G	acceptor_loss	0.9900
15:93045710:C:CT	acceptor_gain	0.9900
15:93045711:G:T	acceptor_gain	0.9900
15:93051987:CCTTA:C	donor_loss	0.9900
15:93051988:CTTA:C	donor_loss	0.9900
15:93051989:TTACC:T	donor_loss	0.9900
15:93051990:TACCT:T	donor_loss	0.9900
15:93051991:A:C	donor_loss	0.9900
15:93051992:CCTT:C	donor_loss	0.9900
15:93051992:CCTTG:C	donor_gain	0.9900
15:93052505:TGG:T	acceptor_gain	0.9900
15:93052508:C:CC	acceptor_gain	0.9900
15:93045152:T:TA	donor_gain	0.9800
15:93052503:GGTGG:G	acceptor_gain	0.9800
15:93052504:GTGG:G	acceptor_gain	0.9800
15:93052508:CT:C	acceptor_loss	0.9800
15:93088913:GCTTA:G	donor_loss	0.9800
15:93088914:CTTAC:C	donor_loss	0.9800
15:93088915:TTACC:T	donor_loss	0.9800
15:93088916:TA:T	donor_loss	0.9800
15:93088917:A:AG	donor_loss	0.9800
15:93088918:C:A	donor_loss	0.9800
15:93052506:GG:G	acceptor_gain	0.9700

AlphaMissense

2929 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:93045657:A:C	Y232D	1.000
15:93052480:C:G	C53S	1.000
15:93052481:A:T	C53S	1.000
15:93045206:A:G	L382P	0.999
15:93045217:G:C	C378W	0.999
15:93045218:C:A	C378F	0.999
15:93045218:C:G	C378S	0.999
15:93045218:C:T	C378Y	0.999
15:93045219:A:G	C378R	0.999
15:93045219:A:T	C378S	0.999
15:93045259:G:C	C364W	0.999
15:93045260:C:G	C364S	0.999
15:93045260:C:T	C364Y	0.999
15:93045261:A:G	C364R	0.999
15:93045261:A:T	C364S	0.999
15:93045406:G:C	C315W	0.999
15:93045407:C:G	C315S	0.999
15:93045407:C:T	C315Y	0.999
15:93045408:A:G	C315R	0.999
15:93045408:A:T	C315S	0.999
15:93045500:C:G	R284P	0.999
15:93045622:G:C	F243L	0.999
15:93045622:G:T	F243L	0.999
15:93045623:A:C	F243C	0.999
15:93045623:A:G	F243S	0.999
15:93045624:A:G	F243L	0.999
15:93052054:A:G	L195P	0.999
15:93052077:C:A	W187C	0.999
15:93052077:C:G	W187C	0.999
15:93052095:G:C	C181W	0.999

dbSNP variants (sampled 300 via entrez): RS1000019197 (15:93042902 T>C), RS1000034720 (15:93038220 G>A), RS1000040970 (15:93080877 C>T), RS1000079982 (15:93054629 G>A), RS1000107740 (15:93079681 A>T), RS1000149604 (15:93047664 T>C,G), RS1000195396 (15:93089273 G>T), RS1000213947 (15:93081839 A>T), RS1000242971 (15:93059023 G>C,T), RS1000338565 (15:93043806 G>A), RS1000370126 (15:93078695 C>A,T), RS1000394767 (15:93065319 T>C,G), RS1000400049 (15:93035743 C>G,T), RS1000412532 (15:93039683 A>G,T), RS1000487578 (15:93065064 G>A)

Disease associations

OMIM: gene MIM:607362 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001518_3	Response to angiotensin II receptor blocker therapy (opposite direction w/ diuretic therapy)	1.000000e-06
GCST001688_2	Type 1 diabetes nephropathy	2.000000e-09
GCST002126_2	Periodontitis (CDC/AAP)	5.000000e-06
GCST002570_2	Overweight status	2.000000e-07
GCST002938_32	Copper levels	6.000000e-06
GCST005368_1	Opioid dependence	1.000000e-08
GCST005368_11	Opioid dependence	3.000000e-08
GCST006585_1708	Blood protein levels	2.000000e-10
GCST006979_941	Heel bone mineral density	6.000000e-10
GCST009367_4	HDL cholesterol levels x short total sleep time interaction (2df test)	2.000000e-09
GCST009391_2146	Metabolite levels	7.000000e-06
GCST010002_104	Refractive error	6.000000e-12
GCST010118_53	Type 2 diabetes	1.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005935	overweight body mass index status
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010551	xanthurenate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630886 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Repulsive guidance molecules

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	7
trichostatin A	affects cotreatment, decreases expression	4
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
Aflatoxin B1	increases expression, increases methylation	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenate	increases abundance, decreases expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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