MEPE

Summary

MEPE (matrix extracellular phosphoglycoprotein, HGNC:13361) is a protein-coding gene on chromosome 4q22.1, encoding Matrix extracellular phosphoglycoprotein (Q9NQ76). Promotes renal phosphate excretion and inhibits intestinal phosphate absorption.

This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 56955 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Moderate, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 109 total
• MANE Select transcript: NM_020203

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13361
Approved symbol	MEPE
Name	matrix extracellular phosphoglycoprotein
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152595
Ensembl biotype	protein_coding
OMIM	605912
Entrez	56955

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000361056, ENST00000395102, ENST00000424957, ENST00000497649, ENST00000511670, ENST00000515821, ENST00000560249

RefSeq mRNA: 6 — MANE Select: NM_020203 NM_001184694, NM_001184695, NM_001184696, NM_001184697, NM_001291183, NM_020203

CCDS: CCDS3625, CCDS77940

Canonical transcript exons

ENST00000361056 — 4 exons

Exon	Start	End
ENSE00002078603	87832969	87833014
ENSE00003631277	87838632	87838685
ENSE00003670571	87834703	87834768
ENSE00003924838	87844977	87846792

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 93.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7200 / max 403.4715, expressed in 100 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48752	1.5723	94
48751	0.1477	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	93.81	gold quality
periodontal ligament	UBERON:0008266	91.26	gold quality
trabecular bone tissue	UBERON:0002483	87.55	gold quality
type B pancreatic cell	CL:0000169	75.11	gold quality
olfactory bulb	UBERON:0002264	75.04	gold quality
pancreatic ductal cell	CL:0002079	74.67	silver quality
cingulate cortex	UBERON:0003027	71.83	gold quality
anterior cingulate cortex	UBERON:0009835	71.82	gold quality
gingival epithelium	UBERON:0001949	71.79	gold quality
cervix squamous epithelium	UBERON:0006922	71.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	71.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.95	gold quality
prefrontal cortex	UBERON:0000451	69.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.18	gold quality
male germ cell	CL:0000015	68.64	gold quality
CA1 field of hippocampus	UBERON:0003881	68.63	gold quality
epithelial cell of pancreas	CL:0000083	68.55	gold quality
middle temporal gyrus	UBERON:0002771	68.51	silver quality
buccal mucosa cell	CL:0002336	68.24	gold quality
sperm	CL:0000019	67.76	gold quality
tongue squamous epithelium	UBERON:0006919	67.34	gold quality
frontal cortex	UBERON:0001870	67.01	gold quality
mucosa of urinary bladder	UBERON:0001259	66.94	gold quality
neocortex	UBERON:0001950	66.82	gold quality
superior frontal gyrus	UBERON:0002661	66.81	gold quality
diaphragm	UBERON:0001103	66.74	gold quality
nasal cavity epithelium	UBERON:0005384	66.56	gold quality
upper arm skin	UBERON:0004263	65.86	gold quality
gingiva	UBERON:0001828	65.82	gold quality
thymus	UBERON:0002370	65.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94
E-HCAD-30	no	35.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

25 targeting MEPE, 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-548P	99.98	72.25	3784
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-10397-3P	97.78	65.70	601
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-136-3P	93.27	66.31	131

Literature-anchored findings (GeneRIF, showing 21)

• Mice deficient in an ortholog of MEPE show increased bone mass and are resistant to aging-related bone loss. (PMID:12421822)
• MEPE/OF45, a new dentin/bone matrix protein and candidate gene for dentin diseases mapping to chromosome 4q21. Expressed during odontogenesis. (PMID:12489176)
• There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving fibroblastic growth factor 23 (FGF23), a phosphate-regulating gene with homologies to (PHEX) and (MEPE)–REVIEW (PMID:12791601)
• MEPE is predominantly expressed by osteocytes in human bone, with significant expression by osteocytes within mineralized bone (PMID:15108058)
• The results are consistent with MEPE being involved in phosphate and bone metabolism in a normal population. (PMID:15292364)
• MEPE is expressed in salivary gland ducts. (PMID:15329369)
• MEPE is expressed on the luminal surface of kidney proximal tubules. (PMID:15954904)
• MEPE expression is higher when cells proliferate, whereas it is downregulated as cells differentiated (PMID:18547474)
• MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract (PMID:19005008)
• MEPE may play a regulatory role in periodontal ligament cell osteogenic differentiation. (PMID:19031789)
• The patterns of expression of FGF-23, MEPE, and DMP1 differ markedly in trabecular bone, suggesting that individual osteocytes may have specialized functions. (PMID:19679205)
• This study demonstrates the importance of posttranslational modification for the site-specific activity of MEPE and its ASARM peptide. (PMID:19998030)
• These results suggest that abnormal MEPE cleavage occurs when PHEX activity is deficient in humans. (PMID:20581062)
• Sclerostin acts through regulation of the PHEX/MEPE axis at the preosteocyte stage and serves as a master regulator of physiologic bone mineralization. (PMID:21312267)
• MEPE or the MEPE-derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute to decreased bone mineralization in Oncogenic osteomalacia patients. (PMID:21739089)
• Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7x10(-7)) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7x10(-7)) appeared to be associated with ischemic stroke. (PMID:21779381)
• results indicated that MEPE appeared to play an important positive role in proliferation and osteogenesis differentiation of DPCs through interaction with downstream signals. (PMID:22341070)
• Results indicate an association of MEPE gene inactivation with decreased survival after DNA damage. (PMID:23570370)
• sequencing identified a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. We performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060). (PMID:30287925)
• Active sites of human MEPE-ASARM regulating bone matrix mineralization. (PMID:32712387)
• MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk. (PMID:33097703)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mepe	ENSMUSG00000053863
rattus_norvegicus	Mepe	ENSRNOG00000002154

Protein

Protein identifiers

Matrix extracellular phosphoglycoprotein — Q9NQ76 (reviewed: Q9NQ76)

Alternative names: Osteoblast/osteocyte factor 45, Osteoregulin

All UniProt accessions (5): Q9NQ76, A0A8I5QJK1, A0A8J9B5S1, D6RAC8, D6RFW6

UniProt curated annotations — full annotation on UniProt →

Function. Promotes renal phosphate excretion and inhibits intestinal phosphate absorption. Promotes bone mineralization by osteoblasts and cartilage mineralization by chondrocytes. Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage. Promotes dental pulp stem cell proliferation and differentiation.

Subunit / interactions. Interacts (via the ASARM motif) with PHEX; the interaction is zinc-dependent.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in urine (at protein level). Expressed by osteoblasts. Expressed by stem cells in dental pulp. Expressed by mesenchymal cells in dental papilla and dental pulp. Expressed in teeth, specifically in decidious dentin. Expressed in ondotoblasts. Expressed in salivary glands. Secreted from oncogenic hypophosphatemic tumors.

Post-translational modifications. Phosphorylated on serine residues in the ASARM motif (in vitro) by FAM20C; the phosphorylation is important for the inhibition of bone mineralization. Cleaved by CTSB/cathepsin B; the cleavage is blocked by metalloprotease PHEX.

Domain organisation. The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage. It can also inhibit dentin mineralization. The dentonin region is sufficient to promote dental pulp stem cell proliferation. It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways.

Similarity. Belongs to the PF07175/osteoregulin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQ76-1	1	yes
Q9NQ76-2	2
Q9NQ76-3	3

RefSeq proteins (6): NP_001171623, NP_001171624, NP_001171625, NP_001171626, NP_001278112, NP_064588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009837	MEPE	Family

Pfam: PF07175

UniProt features (21 total): compositionally biased region 7, region of interest 5, glycosylation site 3, splice variant 2, signal peptide 1, chain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ76-F1	43.45	0.00

Functional residue map

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

Glycosylation sites (3): 256, 477, 478

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 53 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, TGCTGAY_UNKNOWN, chr4q22, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, SHEN_SMARCA2_TARGETS_DN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KANG_AR_TARGETS_DN, AKT_UP_MTOR_DN.V1_DN, AKT_UP.V1_DN, GOMF_EXTRACELLULAR_MATRIX_PROTEIN_BINDING, REACTOME_REGULATION_OF_INSULIN_LIKE_GROWTH_FACTOR_IGF_TRANSPORT_AND_UPTAKE_BY_INSULIN_LIKE_GROWTH_FACTOR_BINDING_PROTEINS_IGFBPS

GO Biological Process (2): skeletal system development (GO:0001501), biomineral tissue development (GO:0031214)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), extracellular matrix protein binding (GO:1990430), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of proteins	2
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
tissue development	1
animal organ development	1
structural molecule activity	1
extracellular matrix	1
protein binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEPE	DMP1	Q13316	981
MEPE	DSPP	Q9NZW4	954
MEPE	PHEX	P78562	924
MEPE	SPP1	P10451	920
MEPE	FGF23	Q9GZV9	863
MEPE	SOST	Q9BQB4	810
MEPE	IBSP	P21815	781
MEPE	SFRP4	Q6FHJ7	770
MEPE	PTH	P01270	685
MEPE	ALPL	P05186	675
MEPE	ENAM	Q9NRM1	674
MEPE	BGLAP	P02818	654
MEPE	AMBN	Q9NP70	592
MEPE	RUNX2	Q13950	590
MEPE	AMTN	Q6UX39	589

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ZXDC	MEPE	psi-mi:“MI:0915”(physical association)	0.560
PHEX	MEPE	psi-mi:“MI:0407”(direct interaction)	0.540
MEPE	PHEX	psi-mi:“MI:0915”(physical association)	0.540
MEPE	ABL1	psi-mi:“MI:0915”(physical association)	0.400
CRK	MEPE	psi-mi:“MI:0915”(physical association)	0.400
MEPE	SRC	psi-mi:“MI:0915”(physical association)	0.400
MEPE	FYN	psi-mi:“MI:0915”(physical association)	0.400
MEPE	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NCK1	MEPE	psi-mi:“MI:0915”(physical association)	0.400
MEPE	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
PLCG1	MEPE	psi-mi:“MI:0915”(physical association)	0.400
MEPE	H1-5	psi-mi:“MI:0915”(physical association)	0.400
MEPE	FN1	psi-mi:“MI:0914”(association)	0.350
MEPE	ZXDC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): FN1 (Affinity Capture-MS), TOMM34 (Affinity Capture-MS), LRP2 (Affinity Capture-MS), MEPE (Two-hybrid), MEPE (Proximity Label-MS), MEPE (Proximity Label-MS), LRP2 (Affinity Capture-MS), FN1 (Affinity Capture-MS), TOMM34 (Affinity Capture-MS), MEPE (Affinity Capture-MS), CHEK1 (Two-hybrid), CHEK1 (Affinity Capture-Western), CHEK1 (Co-localization), MEPE (Affinity Capture-Western)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: Q8K4L6, Q9ES02, Q9NQ76

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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
Downstream signal transduction	6	228.4×	1e-11
FCGR3A-mediated phagocytosis	6	112.3×	6e-10
VEGFA-VEGFR2 Pathway	5	69.6×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	143.3×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	16
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

900 predictions. Top by Δscore:

Variant	Effect	Δscore
4:87834701:A:AG	acceptor_gain	1.0000
4:87834702:G:GG	acceptor_gain	1.0000
4:87834702:GA:G	acceptor_gain	1.0000
4:87834769:G:GG	donor_gain	1.0000
4:87834697:TTACA:T	acceptor_loss	0.9900
4:87834700:C:CG	acceptor_loss	0.9900
4:87834701:AGAGA:A	acceptor_loss	0.9900
4:87834702:G:A	acceptor_loss	0.9900
4:87834702:GAGA:G	acceptor_gain	0.9900
4:87834764:CACCA:C	donor_gain	0.9900
4:87834765:ACCA:A	donor_gain	0.9900
4:87834766:CCA:C	donor_gain	0.9900
4:87834766:CCAG:C	donor_loss	0.9900
4:87834767:CA:C	donor_gain	0.9900
4:87834767:CAGTA:C	donor_loss	0.9900
4:87834768:AGTAA:A	donor_loss	0.9900
4:87834769:GT:G	donor_loss	0.9900
4:87834770:TAAGT:T	donor_loss	0.9900
4:87834771:AAGTA:A	donor_loss	0.9900
4:87834772:A:AC	donor_loss	0.9900
4:87834773:G:A	donor_loss	0.9900
4:87833323:A:T	donor_gain	0.9800
4:87834695:TTTTA:T	acceptor_loss	0.9800
4:87834700:CAG:C	acceptor_gain	0.9700
4:87834701:AGA:A	acceptor_gain	0.9700
4:87834702:GAG:G	acceptor_gain	0.9700
4:87833322:G:GT	donor_gain	0.9600
4:87834696:TTTAC:T	acceptor_loss	0.9600
4:87834702:GAGAT:G	acceptor_gain	0.9600
4:87832948:GCAAA:G	acceptor_gain	0.9500

AlphaMissense

3570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:87845631:T:C	F255L	0.922
4:87845633:C:A	F255L	0.922
4:87845633:C:G	F255L	0.922
4:87845583:A:C	S239R	0.918
4:87845585:C:A	S239R	0.918
4:87845585:C:G	S239R	0.918
4:87846432:A:C	S522R	0.882
4:87846434:C:A	S522R	0.882
4:87846434:C:G	S522R	0.882
4:87845634:A:C	S256R	0.879
4:87845636:T:A	S256R	0.879
4:87845636:T:G	S256R	0.879
4:87846414:A:C	S516R	0.869
4:87846416:T:A	S516R	0.869
4:87846416:T:G	S516R	0.869
4:87846420:A:C	S518R	0.860
4:87846422:T:A	S518R	0.860
4:87846422:T:G	S518R	0.860
4:87845907:T:C	F347L	0.846
4:87845909:T:A	F347L	0.846
4:87845909:T:G	F347L	0.846
4:87845574:T:C	F236L	0.844
4:87845576:T:A	F236L	0.844
4:87845576:T:G	F236L	0.844
4:87845580:G:C	G238R	0.843
4:87845917:T:C	L350P	0.841
4:87834748:A:C	S12R	0.807
4:87834750:T:A	S12R	0.807
4:87834750:T:G	S12R	0.807
4:87845895:G:C	G343R	0.806

dbSNP variants (sampled 300 via entrez): RS1000009864 (4:87830809 G>A), RS1000046417 (4:87819830 C>T), RS1000074794 (4:87829410 T>G), RS1000289485 (4:87820071 T>G), RS1000326586 (4:87825694 CT>C,CTT), RS1000366041 (4:87840315 C>A,T), RS1000381868 (4:87831891 G>C,T), RS1000578073 (4:87823992 TTC>T), RS1000655887 (4:87825460 T>C), RS10007111 (4:87828549 A>G,T), RS1000827025 (4:87836548 CT>C), RS1000833093 (4:87836959 T>G), RS1000964286 (4:87842753 G>A), RS1001127603 (4:87834929 C>A,T), RS1001160339 (4:87835109 T>C)

Disease associations

OMIM: gene MIM:605912 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Moderate	Autosomal dominant

Mondo (1): nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000494_14	Bone mineral density (spine)	2.000000e-08
GCST000495_2	Bone mineral density (hip)	8.000000e-07
GCST001157_1	Cardiovascular disease risk factors	3.000000e-07
GCST001482_24	Lumbar spine bone mineral density	1.000000e-27
GCST001713_23	Dental caries	7.000000e-08
GCST002276_1	Bone mineral density	2.000000e-09
GCST002494_8	Bone mineral density (paediatric, total body less head)	3.000000e-06
GCST006288_208	Heel bone mineral density	3.000000e-11
GCST006288_315	Heel bone mineral density	4.000000e-06
GCST006288_526	Heel bone mineral density	3.000000e-17
GCST006979_441	Heel bone mineral density	4.000000e-21
GCST006979_442	Heel bone mineral density	1.000000e-18
GCST006979_443	Heel bone mineral density	1.000000e-38
GCST006979_444	Heel bone mineral density	2.000000e-60
GCST007935_4	Medication use (drugs affecting bone structure and mineralization)	1.000000e-08
GCST011496_2	Abdominal aortic aneurysm	2.000000e-08
GCST012338_13	Gout	1.000000e-21
GCST012339_7	Gout vs asymptomatic hyperuricemia	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0009936	Drugs affecting bone structure and mineralization use measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
pirinixic acid	affects binding, decreases expression, increases activity	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
Phosphates	affects metabolic processing	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations