GREM2

Summary

GREM2 (gremlin 2, DAN family BMP antagonist, HGNC:17655) is a protein-coding gene on chromosome 1q43, encoding Gremlin-2 (Q9H772). Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members.

This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation.

Source: NCBI Gene 64388 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tooth agenesis, selective, 9 (Limited, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• Phenotypes (HPO): 25
• MANE Select transcript: NM_022469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17655
Approved symbol	GREM2
Name	gremlin 2, DAN family BMP antagonist
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	Prdc, FLJ21195, CKTSF1B2, DAND3
Ensembl gene	ENSG00000180875
Ensembl biotype	protein_coding
OMIM	608832
Entrez	64388

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000318160, ENST00000859904, ENST00000859905, ENST00000859906, ENST00000942417

RefSeq mRNA: 1 — MANE Select: NM_022469 NM_022469

CCDS: CCDS31070

Canonical transcript exons

ENST00000318160 — 2 exons

Exon	Start	End
ENSE00001238452	240489573	240493476
ENSE00001442038	240611884	240612155

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.77.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0987 / max 278.2436, expressed in 638 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18259	5.4885	547
18258	1.1899	356
18257	0.4202	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	92.77	gold quality
rectum	UBERON:0001052	87.46	gold quality
right lobe of liver	UBERON:0001114	84.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.92	gold quality
saphenous vein	UBERON:0007318	82.70	gold quality
mucosa of stomach	UBERON:0001199	82.43	gold quality
colonic epithelium	UBERON:0000397	82.42	gold quality
liver	UBERON:0002107	80.48	gold quality
stromal cell of endometrium	CL:0002255	80.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.12	gold quality
colon	UBERON:0001155	79.70	gold quality
large intestine	UBERON:0000059	79.38	gold quality
intestine	UBERON:0000160	79.21	gold quality
small intestine	UBERON:0002108	78.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.43	gold quality
transverse colon	UBERON:0001157	78.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.40	gold quality
vermiform appendix	UBERON:0001154	77.73	gold quality
pharyngeal mucosa	UBERON:0000355	77.55	gold quality
body of stomach	UBERON:0001161	76.46	gold quality
caecum	UBERON:0001153	76.40	gold quality
lower esophagus mucosa	UBERON:0035834	76.39	gold quality
stomach	UBERON:0000945	75.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.90	gold quality
colonic mucosa	UBERON:0000317	74.30	gold quality
prefrontal cortex	UBERON:0000451	74.13	gold quality
oral cavity	UBERON:0000167	74.09	gold quality
pylorus	UBERON:0001166	73.56	gold quality
superior surface of tongue	UBERON:0007371	73.45	gold quality
esophagus mucosa	UBERON:0002469	73.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	92.72
E-MTAB-7037	no	387.43
E-ANND-3	no	3.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

139 targeting GREM2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-513A-5P	100.00	69.77	2465
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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 19)

• Through regulation of bone morphogenetic protein signaling, GREM2 is required for cardiac laterality and atrial differentiation during embryonic development. (PMID:23223679)
• and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk. (PMID:23437003)
• The minor allele of rs4454537 is significantly associated with low bone density at the total hip of southern Chinese people. Our study further suggests GREM2 as a novel susceptibility gene for osteoporosis. (PMID:23902946)
• GREM2 variants have been identified in atrial fibrillation cohort studies, demonstrating abnormalities in cardiac excitation - supra ventricular tachycardia and atrial fibrillation. (PMID:25443231)
• Gremlin 2 inhibits adipocyte differentiation through activation of Wnt/beta-catenin signaling (PMID:26239165)
• mutations associated with tooth malformations (PMID:26416033)
• This study showed that si-Grem2 increased the BMP-2-induced osteogenic differentiation of hBMSCs via the BMP-2/Smad/Runx2 pathway. (PMID:27335248)
• The structure of Grem2-GDF5 complex has revealed a number of key findings for DAN-family mediated BMP2 inhibition. (PMID:27524626)
• The present study shows that the Grem2 heparin/HS and BMP2-binding epitopes are unique and independent, where the Grem2-BMP2 complex exhibits a significant increase in binding affinity toward heparin moieties that appear to be partially independent of the Grem2 heparin/HS-binding epitope. (PMID:28104757)
• Data show that the GREMLIN 2 (GREM2) expression during Induced Pluripotent Stem Cell (hiPS) cell cardiac differentiation follows the expression pattern of cardiac-specific genes. (PMID:28125926)
• Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly. (PMID:28992378)
• TT genotype of the rs4454537 polymorphism protective against the development of osteoporosis (PMID:30014930)
• Significant associations were found between individual SNPs and SNP combinations in WNT10A, WNT10B and GREM2 SNPs with isolated tooth agenesis. (PMID:30246922)
• Grem2 increased the phosphorylation of Smad2/3 and decreased the phosphorylation of Smad1/5/8 (PMID:30831151)
• Association of Gremlin-2 gene polymorphisms with osteoporosis risk in Chinese postmenopausal women. (PMID:32297643)
• Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-beta signaling pathway. (PMID:33144675)
• Functional characterization of ATF1, GREM2 AND WNT10B variants associated with tooth agenesis. (PMID:33369218)
• GREM2 is associated with human central obesity and inhibits visceral preadipocyte browning. (PMID:35349825)
• MiR-103a-3p Contributes to the Progression of Colorectal Cancer by Regulating GREM2 Expression. (PMID:35619575)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grem2a	ENSDARG00000056057
danio_rerio	grem2b	ENSDARG00000103092
mus_musculus	Grem2	ENSMUSG00000050069
rattus_norvegicus	Grem2	ENSRNOG00000003616
caenorhabditis_elegans		WBGENE00009389

Paralogs (2): NBL1 (ENSG00000158747), GREM1 (ENSG00000166923)

Protein

Protein identifiers

Gremlin-2 — Q9H772 (reviewed: Q9H772)

Alternative names: Cysteine knot superfamily 1, BMP antagonist 2, DAN domain family member 3, Protein related to DAN and cerberus

All UniProt accessions (1): Q9H772

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.

Subunit / interactions. Homodimer. Interacts with BMP2, BMP4 and BMP7, but has lower affinity for BMP7 than for BMP2 and BMP4. Binds heparin; this impairs the interaction with BMP2.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated.

Disease relevance. Tooth agenesis, selective, 9 (STHAG9) [MIM:617275] A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG9 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DAN family.

RefSeq proteins (1): NP_071914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004133	DAN_dom	Domain
IPR006207	Cys_knot_C	Domain
IPR017159	Gremlin-1/2	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF03045

UniProt features (15 total): sequence variant 4, disulfide bond 4, sequence conflict 2, glycosylation site 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H772-F1	79.38	0.44

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): 73–123, 87–137, 97–155, 101–157

Glycosylation sites (2): 40, 161

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP

MSigDB gene sets: 211 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_BODY_MORPHOGENESIS, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_RESPONSE_TO_PEPTIDE, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, GOBP_REGULATION_OF_RECEPTOR_BINDING, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_SPECIFICATION_OF_SYMMETRY, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, TRAYNOR_RETT_SYNDROM_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GERY_CEBP_TARGETS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_EXTRACELLULAR_REGULATION_OF_SIGNAL_TRANSDUCTION

GO Biological Process (6): embryonic body morphogenesis (GO:0010172), cytokine-mediated signaling pathway (GO:0019221), obsolete sequestering of BMP from receptor via BMP binding (GO:0038098), determination of dorsal identity (GO:0048263), regulation of cytokine activity (GO:0060300), negative regulation of BMP signaling pathway (GO:0030514)

GO Molecular Function (5): cytokine activity (GO:0005125), heparin binding (GO:0008201), BMP binding (GO:0036122), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by TGFB family members	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
body morphogenesis	1
embryonic morphogenesis	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
dorsal/ventral pattern formation	1
determination of dorsal/ventral asymmetry	1
cytokine activity	1
regulation of signaling receptor activity	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
receptor ligand activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
cytokine binding	1
protein binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GREM2	BMP2	P12643	897
GREM2	GDF9	O60383	805
GREM2	BMP4	P12644	789
GREM2	SOST	Q9BQB4	785
GREM2	BMP7	P18075	779
GREM2	CHRD	Q9H2X0	737
GREM2	BMP6	P22004	727
GREM2	NOG	Q13253	675
GREM2	GDF5	P43026	655
GREM2	SHH	Q15465	609
GREM2	BMP5	P22003	605
GREM2	FST	P19883	584
GREM2	DAND5	Q8N907	558
GREM2	CHRDL1	Q9BU40	544
GREM2	SOSTDC1	Q6X4U4	543

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (34): GREM2 (Affinity Capture-RNA), ZMYND19 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), WDHD1 (Affinity Capture-MS), LRP2 (Affinity Capture-MS), WAPAL (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), KBTBD6 (Affinity Capture-MS), MAEA (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), LDLR (Affinity Capture-MS), FBN2 (Affinity Capture-MS), FERMT2 (Affinity Capture-MS)

ESM2 similar proteins: A0MTF4, M3X9S6, O35757, O35793, O54693, O60565, O70326, O73753, O73754, O73755, O88273, P09858, P12034, P15656, P20827, P21214, P27090, P30371, P39905, P41271, P48540, P48807, P49767, P50291, P61811, P61812, P97401, P97553, P97953, Q06880, Q06AS9, Q07257, Q07731, Q20FD0, Q38L25, Q61477, Q6DF53, Q6NW40, Q6NZ13, Q7TQ33

Diamond homologs: O35793, O55233, O60565, O70326, O73753, O73754, O73755, O88273, O95813, P41271, P70041, Q06880, Q28H35, Q61477, Q6DF53, Q6NZ13, Q76LW6, Q800X4, Q8WNY1, Q90YC9, Q9H772, Q8N907, Q07G34, Q9PWB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
374885	NM_022469.4(GREM2):c.408G>T (p.Glu136Asp)	Pathogenic

SpliceAI

1435 predictions. Top by Δscore:

Variant	Effect	Δscore
1:240493473:CATC:C	acceptor_gain	1.0000
1:240493472:ACATC:A	acceptor_gain	0.9900
1:240493473:CATCC:C	acceptor_gain	0.9900
1:240493475:TC:T	acceptor_gain	0.9900
1:240493476:CC:C	acceptor_gain	0.9900
1:240493476:CCTG:C	acceptor_loss	0.9900
1:240493477:C:CC	acceptor_gain	0.9900
1:240493478:T:G	acceptor_loss	0.9900
1:240495166:TAA:T	donor_gain	0.9900
1:240493474:ATC:A	acceptor_gain	0.9800
1:240493484:C:CT	acceptor_gain	0.9800
1:240493485:G:T	acceptor_gain	0.9800
1:240599728:TGAAA:T	donor_gain	0.9800
1:240611878:GCGTA:G	donor_loss	0.9800
1:240611879:CGTAC:C	donor_loss	0.9800
1:240611880:GTAC:G	donor_loss	0.9800
1:240611881:TACCT:T	donor_loss	0.9800
1:240611882:AC:A	donor_loss	0.9800
1:240611883:C:CA	donor_loss	0.9800
1:240611333:C:A	donor_gain	0.9600
1:240544996:AGTTT:A	donor_gain	0.9400
1:240601072:T:TA	donor_gain	0.9400
1:240545704:A:AC	donor_gain	0.9300
1:240545705:C:CC	donor_gain	0.9300
1:240586423:CTGAG:C	donor_gain	0.9300
1:240586424:TGAGT:T	donor_gain	0.9300
1:240586425:GAGTG:G	donor_gain	0.9300
1:240586426:AGTGA:A	donor_gain	0.9300
1:240493480:C:CT	acceptor_gain	0.9200
1:240545880:A:C	acceptor_gain	0.9100

AlphaMissense

1096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:240493005:G:C	C157W	1.000
1:240493006:C:G	C157S	1.000
1:240493006:C:T	C157Y	1.000
1:240493007:A:G	C157R	1.000
1:240493007:A:T	C157S	1.000
1:240493011:G:C	C155W	1.000
1:240493012:C:A	C155F	1.000
1:240493012:C:G	C155S	1.000
1:240493012:C:T	C155Y	1.000
1:240493013:A:G	C155R	1.000
1:240493013:A:T	C155S	1.000
1:240493067:A:G	C137R	1.000
1:240493107:G:C	C123W	1.000
1:240493108:C:A	C123F	1.000
1:240493108:C:G	C123S	1.000
1:240493108:C:T	C123Y	1.000
1:240493109:A:G	C123R	1.000
1:240493109:A:T	C123S	1.000
1:240493117:C:T	C120Y	1.000
1:240493118:A:G	C120R	1.000
1:240493125:G:C	F117L	1.000
1:240493125:G:T	F117L	1.000
1:240493126:A:C	F117C	1.000
1:240493126:A:G	F117S	1.000
1:240493127:A:G	F117L	1.000
1:240493159:A:G	I106T	1.000
1:240493159:A:T	I106N	1.000
1:240493164:G:C	F104L	1.000
1:240493164:G:T	F104L	1.000
1:240493165:A:C	F104C	1.000

dbSNP variants (sampled 300 via entrez): RS1000002690 (1:240606234 C>T), RS1000005764 (1:240554813 C>G), RS1000035313 (1:240606472 C>G,T), RS1000080553 (1:240559432 C>T), RS1000089538 (1:240517721 A>C), RS1000098960 (1:240519466 C>T), RS1000105418 (1:240510878 T>C), RS1000112483 (1:240596339 A>T), RS1000140980 (1:240504698 C>T), RS1000160948 (1:240533905 C>G,T), RS1000172396 (1:240504380 C>G,T), RS1000182593 (1:240573822 T>C,G), RS1000214536 (1:240585206 A>T), RS1000229081 (1:240580617 C>A), RS1000236829 (1:240560567 G>A)

Disease associations

OMIM: gene MIM:608832 | disease phenotypes: MIM:617275

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
tooth agenesis, selective, 9	Limited	AD

Mondo (1): tooth agenesis, selective, 9 (MONDO:0014999)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000202	Orofacial cleft
HP:0000677	Oligodontia
HP:0000679	Taurodontia
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion
HP:0000690	Agenesis of maxillary lateral incisor
HP:0000691	Microdontia
HP:0000696	Delayed eruption of permanent teeth
HP:0001592	Selective tooth agenesis
HP:0005216	Impaired mastication
HP:0006289	Agenesis of central incisor
HP:0006297	Enamel hypoplasia
HP:0006336	Short dental root
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0006344	Abnormal primary molar morphology
HP:0006482	Abnormal dental morphology
HP:0011051	Agenesis of premolar
HP:0011053	Agenesis of mandibular premolar
HP:0011056	Agenesis of first permanent molar tooth
HP:0011078	Abnormality of canine
HP:0011219	Short face
HP:0012472	Eclabion

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001361_2	Ankle-brachial index	7.000000e-06
GCST001491_28	Immune response to smallpox vaccine (IL-6)	2.000000e-07
GCST007014_3	Lumbar spine bone mineral density (trabecular)	1.000000e-11
GCST007015_12	Lumbar spine bone mineral density (integral)	1.000000e-07
GCST008148_1	Response to allopurinol in gout (change in serum uric acid levels)	3.000000e-06
GCST009115_1	Heel bone mineral density variance	8.000000e-14
GCST009120_1	Heel bone mineral density	1.000000e-94
GCST90002390_343	Mean corpuscular hemoglobin	4.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003912	ankle brachial index
EFO:0004645	response to vaccine
EFO:0007620	volumetric bone mineral density
EFO:0004761	uric acid measurement
EFO:0009270	heel bone mineral density
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10802887	Efficacy	3	allopurinol
rs1934341	Efficacy	3	allopurinol
rs4659982	Efficacy	3	allopurinol
rs77567654	Efficacy	3	allopurinol

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs77567654	GREM2	3	0.00	1	allopurinol
rs1934341	GREM2	3	0.00	1	allopurinol
rs10802887	GREM2	3	0.00	1	allopurinol
rs4659982	GREM2	3	0.00	1	allopurinol

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Dexamethasone	decreases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	affects expression, decreases methylation	2
8-Bromo Cyclic Adenosine Monophosphate	increases expression	2
GSK-J4	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
Dasatinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Air Pollutants	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Niclosamide	decreases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	increases expression	1
Vitallium	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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