GDF3

Summary

GDF3 (growth differentiation factor 3, HGNC:4218) is a protein-coding gene on chromosome 12p13.31, encoding Growth/differentiation factor 3 (Q9NR23). Growth factor involved in early embryonic development and adipose-tissue homeostasis.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein plays a role ocular and skeletal development. Mutations in this gene are associated with microphthalmia, coloboma, and skeletal abnormalities in human patients.

Source: NCBI Gene 9573 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated Klippel-Feil syndrome (Supportive, GenCC) — +5 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 91 total — 2 likely-pathogenic
• Phenotypes (HPO): 49
• MANE Select transcript: NM_020634

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4218
Approved symbol	GDF3
Name	growth differentiation factor 3
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184344
Ensembl biotype	protein_coding
OMIM	606522
Entrez	9573

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329913

RefSeq mRNA: 1 — MANE Select: NM_020634 NM_020634

CCDS: CCDS8581

Canonical transcript exons

ENST00000329913 — 2 exons

Exon	Start	End
ENSE00001307437	7695461	7695775
ENSE00001320592	7689784	7690704

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 83.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.9990 / max 1697.8887, expressed in 127 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129281	2.7491	123
129280	0.1884	43
129282	0.0616	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.48	gold quality
type B pancreatic cell	CL:0000169	73.43	gold quality
olfactory bulb	UBERON:0002264	73.28	gold quality
superficial temporal artery	UBERON:0001614	68.64	gold quality
diaphragm	UBERON:0001103	67.83	gold quality
tibialis anterior	UBERON:0001385	66.18	silver quality
mucosa of paranasal sinus	UBERON:0005030	63.98	gold quality
ileal mucosa	UBERON:0000331	63.52	silver quality
metanephros cortex	UBERON:0010533	63.43	gold quality
triceps brachii	UBERON:0001509	63.38	gold quality
gluteal muscle	UBERON:0002000	63.31	gold quality
tongue squamous epithelium	UBERON:0006919	60.69	gold quality
orbitofrontal cortex	UBERON:0004167	60.22	gold quality
lateral globus pallidus	UBERON:0002476	59.53	gold quality
quadriceps femoris	UBERON:0001377	59.47	gold quality
pancreatic ductal cell	CL:0002079	59.19	silver quality
thymus	UBERON:0002370	58.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.65	gold quality
vastus lateralis	UBERON:0001379	58.58	gold quality
nasal cavity epithelium	UBERON:0005384	58.54	gold quality
deltoid	UBERON:0001476	58.17	gold quality
layer of synovial tissue	UBERON:0007616	57.17	gold quality
heart right ventricle	UBERON:0002080	57.10	gold quality
metanephros	UBERON:0000081	56.25	gold quality
amniotic fluid	UBERON:0000173	55.46	gold quality
substantia nigra pars compacta	UBERON:0001965	54.68	gold quality
biceps brachii	UBERON:0001507	54.65	gold quality
squamous epithelium	UBERON:0006914	54.60	gold quality
gingival epithelium	UBERON:0001949	54.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	771.06
E-ANND-3	no	1.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP1, NANOG, NR5A2

Literature-anchored findings (GeneRIF, showing 16)

• Present data suggested that GDF3 might play important roles in the central nervous system (CNS), especially in cerebral cortex, hippocampus and cerebellum, and it shed new light on further research of GDF3 in the central nervous system. (PMID:16126341)
• GDF3 regulates both of the two major characteristics of embryonic stem cells: the ability to maintain the undifferentiated state and the ability to differentiate into the full spectrum of cell types. (PMID:16339188)
• GDF3 regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the ALK7 receptor (PMID:18480259)
• GDF3 is either a bi-functional TGF-beta ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions. (PMID:18823971)
• GDF3 positivity is helpful in the diagnosis of yolk sac tumor (PMID:19396148)
• Mutation of GDF3 causes ocular and skeletal anomalies. (PMID:19864492)
• the conditioned medium from CHO-GDF3 could reduce PC12 cell growth and induce cell differentiation (PMID:21805089)
• Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells. (PMID:22305102)
• GDF3 expression level was significantly down-regulated in breast cancer tissues compared to the surrounding nontumorous tissues. (PMID:22488170)
• first evidence that NANOG is a transcriptional activator of the expression of the oncogenic growth factor GDF3 in embryonic carcinoma cells (PMID:22963770)
• The results expand the spectrum of mutations associated with CHDs and first suggest the potentially disease-related GDF3 gene variant in the pathogenesis of CHDs. (PMID:25372014)
• OCT4 plays a role as a transcriptional activator for GDF3 transcription in pluripotent human embryonic carcinoma NCCIT cells and contributes to the understanding of the molecular networks of stem cell regulators in germ cell-derived pluripotency and tumorigenesis. (PMID:27803451)
• the 4 of the 5 variants in [i]GDF3[/i] gene contribute different pathogenicity in congenital scoliosis, which may provide molecular evidence for clinical genetic testing. (PMID:29735971)
• Increased Serum Levels of Growth-Differentiation Factor 3 (GDF3) and Inflammasome-Related Markers in Pregnant Women during Acute Zika Virus Infection. (PMID:35632746)
• Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction. (PMID:36484260)
• [Expression and significance analysis of GDF3 in testicular cancer based on TCGA and GTEx databases]. (PMID:38639949)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gdf3	ENSMUSG00000030117
rattus_norvegicus	Gdf3	ENSRNOG00000015331

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Growth/differentiation factor 3 — Q9NR23 (reviewed: Q9NR23)

All UniProt accessions (1): Q9NR23

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor involved in early embryonic development and adipose-tissue homeostasis. During embryogenesis controls formation of anterior visceral endoderm and mesoderm and the establishment of anterior-posterior identity through a receptor complex comprising the receptor ACVR1B and the coreceptor CRIPTO. Regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the receptor complex based on ACVR1C and CRIPTO/Cripto.

Subunit / interactions. Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.

Subcellular location. Secreted. Cytoplasm.

Post-translational modifications. Synthesized as large precursor molecule that undergo proteolytic cleavage, releasing the pro-domain from the active, receptor binding, C-terminal region of the molecule.

Disease relevance. Klippel-Feil syndrome 3, autosomal dominant (KFS3) [MIM:613702] A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. The disease is caused by variants affecting the gene represented in this entry. Microphthalmia/Coloboma 6 (MCOPCB6) [MIM:613703] A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The disease is caused by variants affecting the gene represented in this entry. Microphthalmia, isolated, 7 (MCOP7) [MIM:613704] A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. In contrast to other members of this family, cannot be disulfide-linked due to an atypical cysteine knot configuration, where the fourth cysteine is missing. This fourth cysteine is involved in an inter-molecular bridge to stabilize the active form of homodimeric or heterodimeric signaling molecules.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_065685* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019

UniProt features (14 total): sequence variant 6, disulfide bond 3, glycosylation site 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR23-F1	82.72	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 (3): 264–329, 293–361, 297–363

Glycosylation sites (2): 112, 306

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_AXIS_SPECIFICATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_RESPONSE_TO_DIETARY_EXCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_PRIMITIVE_STREAK_FORMATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOMF_GROWTH_FACTOR_ACTIVITY

GO Biological Process (19): skeletal system development (GO:0001501), eye development (GO:0001654), in utero embryonic development (GO:0001701), response to dietary excess (GO:0002021), endoderm development (GO:0007492), mesoderm development (GO:0007498), regulation of cell fate commitment (GO:0010453), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), notochord development (GO:0030903), somite rostral/caudal axis specification (GO:0032525), positive regulation of fat cell differentiation (GO:0045600), negative regulation of epidermal cell differentiation (GO:0045605), negative regulation of myoblast differentiation (GO:0045662), formation of anatomical boundary (GO:0048859), primitive streak formation (GO:0090009), signal transduction (GO:0007165), animal organ development (GO:0048513), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092)

GO Molecular Function (3): cytokine activity (GO:0005125), growth factor activity (GO:0008083), protein kinase binding (GO:0019901)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	2
regulation of cellular process	2
anterior/posterior axis specification	2
anatomical structure formation involved in morphogenesis	2
receptor ligand activity	2
cellular anatomical structure	2
system development	1
sensory organ development	1
visual system development	1
chordate embryonic development	1
response to nutrient levels	1
energy homeostasis	1
cell fate commitment	1
regulation of developmental process	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	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
embryonic organ development	1
embryonic axis specification	1
somitogenesis	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
epidermal cell differentiation	1
negative regulation of epithelial cell differentiation	1
regulation of epidermal cell differentiation	1
negative regulation of epidermis development	1
myoblast differentiation	1
negative regulation of cell differentiation	1
regulation of myoblast differentiation	1
gastrulation with mouth forming second	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
anatomical structure development	1
cell surface receptor protein serine/threonine kinase signaling pathway	1

Protein interactions and networks

STRING

1090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDF3	ACVR1C	Q8NER5	979
GDF3	CRIPTO	P13385	964
GDF3	DDX1	Q92499	769
GDF3	VSX2	P58304	748
GDF3	NANOG	Q9H9S0	737
GDF3	DPPA3	Q6W0C5	694
GDF3	DPPA4	Q7L190	672
GDF3	POU5F1	P31359	667
GDF3	ACVR1B	P36896	648
GDF3	DPPA2	Q7Z7J5	644
GDF3	SOX2	P48431	641
GDF3	CD9	P21926	637
GDF3	UTF1	Q5T230	630
GDF3	LEFTY1	O75610	628
GDF3	LEFTY2	O00292	610

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GDF3	IDH3B	psi-mi:“MI:0914”(association)	0.350
PQBP1	ANK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): IDH3B (Affinity Capture-MS), PPM1A (Affinity Capture-MS), IDH3B (Affinity Capture-MS), PPM1A (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), GDF3 (Reconstituted Complex), IDH3B (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), CALR (Affinity Capture-MS), SELO (Affinity Capture-MS), VPS39 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), GDF3 (Affinity Capture-MS), NUP54 (Affinity Capture-MS), NUPL1 (Affinity Capture-MS)

ESM2 similar proteins: B3EWX6, B4ESA2, F5HBX1, F5HC71, F5HCJ2, O00175, O55038, O88324, P09534, P0C6B7, P17150, P22362, P27784, P51670, P70107, P82140, P82172, Q07104, Q16661, Q30KJ2, Q30KJ3, Q30KJ8, Q30KM9, Q30KP8, Q32ZF3, Q32ZH9, Q32ZI1, Q68FP3, Q68Y86, Q6TU36, Q77MQ6, Q7TPG6, Q7TPG8, Q7Z5A8, Q7Z5A9, Q8BLC3, Q8BVB5, Q8K4N3, Q8N2G4, Q8TAA1

Diamond homologs: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, A8E7N9, G5EEL5, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O46576, O61643, O95390, O95393, P09534, P12644, P12645, P17491, P18075, P20722, P20863, P22003, P22004, P22444, P23359, P27091, P27539, P35621, P43026, P43027, P43028, P43029, P48970

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SOX2/POU5F1	“up-regulates quantity by expression”	GDF3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	60
Likely benign	12
Benign	14

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
191030	NM_020634.3(GDF3):c.232G>C (p.Val78Leu)	Likely pathogenic
423808	NM_020634.3(GDF3):c.914T>G (p.Leu305Arg)	Likely pathogenic

SpliceAI

152 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7690705:C:CG	acceptor_loss	1.0000
12:7695455:CCTTA:C	donor_loss	1.0000
12:7695456:CTTA:C	donor_loss	1.0000
12:7695457:TTACC:T	donor_loss	1.0000
12:7695458:TAC:T	donor_loss	1.0000
12:7695459:ACC:A	donor_loss	1.0000
12:7690700:GAAAC:G	acceptor_gain	0.9900
12:7690701:AAAC:A	acceptor_gain	0.9900
12:7690702:AAC:A	acceptor_gain	0.9900
12:7690705:C:CC	acceptor_gain	0.9900
12:7690701:AAACC:A	acceptor_gain	0.9800
12:7690702:AACC:A	acceptor_gain	0.9800
12:7690703:AC:A	acceptor_gain	0.9800
12:7690703:ACCTA:A	acceptor_gain	0.9800
12:7690704:CC:C	acceptor_gain	0.9800
12:7690704:CCTAG:C	acceptor_gain	0.9800
12:7690705:C:A	acceptor_gain	0.9800
12:7690709:A:C	acceptor_gain	0.9800
12:7695459:A:AC	donor_gain	0.9800
12:7695459:AC:A	donor_gain	0.9800
12:7695460:C:CC	donor_gain	0.9800
12:7695460:CC:C	donor_gain	0.9800
12:7690706:T:G	acceptor_gain	0.9700
12:7690709:A:AC	acceptor_gain	0.9700
12:7695460:CCTTG:C	donor_gain	0.9300
12:7695488:T:A	donor_gain	0.8800
12:7690272:A:T	acceptor_gain	0.8600
12:7695460:CCTT:C	donor_gain	0.8600
12:7695460:CCT:C	donor_gain	0.8500
12:7692303:G:A	donor_gain	0.8000

AlphaMissense

2382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7689988:A:G	C329R	0.993
12:7690094:G:C	C293W	0.993
12:7689986:A:C	C329W	0.992
12:7690095:C:G	C293S	0.992
12:7690096:A:T	C293S	0.992
12:7689987:C:G	C329S	0.991
12:7689988:A:T	C329S	0.991
12:7689987:C:T	C329Y	0.990
12:7690110:A:C	F288C	0.990
12:7690095:C:T	C293Y	0.989
12:7690083:C:G	C297S	0.988
12:7690084:A:T	C297S	0.988
12:7690109:G:C	F288L	0.988
12:7690109:G:T	F288L	0.988
12:7690111:A:G	F288L	0.988
12:7690110:A:G	F288S	0.987
12:7689900:A:T	V358D	0.986
12:7690084:A:G	C297R	0.986
12:7690096:A:G	C293R	0.985
12:7690182:C:G	C264S	0.985
12:7690183:A:T	C264S	0.985
12:7690155:A:C	F273C	0.984
12:7690130:C:A	W281C	0.983
12:7690130:C:G	W281C	0.983
12:7690139:C:A	W278C	0.983
12:7690139:C:G	W278C	0.983
12:7689987:C:A	C329F	0.982
12:7690095:C:A	C293F	0.982
12:7689892:A:G	C361R	0.981
12:7689885:C:G	C363S	0.980

dbSNP variants (sampled 300 via entrez): RS1000268324 (12:7697467 T>C), RS1000299474 (12:7697681 A>C), RS1000996246 (12:7696822 T>A), RS1001006373 (12:7691365 A>G), RS1001548319 (12:7691585 A>C), RS1002280898 (12:7691867 C>T), RS1002333162 (12:7692000 C>T), RS1002631298 (12:7697366 C>T), RS1002953664 (12:7694319 T>C), RS1003285658 (12:7692947 T>C), RS1003341056 (12:7693277 A>T), RS1004246967 (12:7689333 C>T), RS1004297893 (12:7693843 C>T), RS1004623848 (12:7694735 G>C), RS1005222867 (12:7696190 C>A,G,T)

Disease associations

OMIM: gene MIM:606522 | disease phenotypes: MIM:613702, MIM:613703, MIM:613704, MIM:218340

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated Klippel-Feil syndrome	Supportive	Autosomal dominant
isolated anophthalmia-microphthalmia syndrome	Supportive	Autosomal dominant
microphthalmia, isolated, with coloboma	Supportive	Autosomal dominant
Klippel-Feil syndrome 3, autosomal dominant	Limited	Autosomal dominant
microphthalmia, isolated, with coloboma 6	Limited	Autosomal dominant
isolated microphthalmia 7	Limited	Autosomal dominant

Mondo (8): Klippel-Feil syndrome 3, autosomal dominant (MONDO:0013375), scoliosis (MONDO:0005392), microphthalmia, isolated, with coloboma 6 (MONDO:0013376), isolated microphthalmia 7 (MONDO:0013377), temtamy syndrome (MONDO:0009033), (MONDO:0016520), isolated anophthalmia-microphthalmia syndrome (MONDO:0016764), microphthalmia, isolated, with coloboma (MONDO:0000170)

Orphanet (4): Isolated Klippel-Feil syndrome (Orphanet:2345), Colobomatous microphthalmia (Orphanet:98938), Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542), Temtamy syndrome (Orphanet:1777)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000086	Ectopic kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000175	Cleft palate
HP:0000324	Facial asymmetry
HP:0000365	Hearing impairment
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000772	Abnormal rib morphology
HP:0000912	Sprengel anomaly
HP:0000925	Abnormality of the vertebral column
HP:0001291	Abnormal cranial nerve morphology
HP:0001629	Ventricular septal defect
HP:0002023	Anal atresia
HP:0002162	Low posterior hairline
HP:0002315	Headache
HP:0002414	Spina bifida
HP:0002650	Scoliosis
HP:0002943	Thoracic scoliosis
HP:0003043	Abnormal shoulder morphology
HP:0003298	Spina bifida occulta
HP:0003416	Spinal canal stenosis
HP:0003577	Congenital onset
HP:0004374	Hemiplegia/hemiparesis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001859_30	Thiazide-induced adverse metabolic effects in hypertensive patients	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D012600	Scoliosis	C05.116.900.800.875
C537463	Microphthalmia associated with colobomatous cyst (supp.)
C536959	Temtamy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Paraquat	affects expression, affects reaction, increases expression	2
bisphenol A	affects expression, affects reaction	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects expression	1
Bucladesine	affects expression, affects reaction	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methapyrilene	increases methylation	1
Methylmercury Compounds	affects expression, affects reaction	1
Tretinoin	decreases expression	1
Triclosan	decreases reaction, increases expression	1
Valproic Acid	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00508066	PHASE4	COMPLETED	Continuous Local Infusion of Anesthetic at the Incisional Site for Scoliosis Surgery
NCT00510575	PHASE4	COMPLETED	Surgical Outcomes Using Variable Rod Diameters in the Treatment of Idiopathic Scoliosis
NCT00768313	PHASE4	WITHDRAWN	Phase IV Comparing Rods of Yield Strengths to Correct Adolescent Idiopathic Scoliosis.
NCT00880607	PHASE4	COMPLETED	Intrathecal Morphine Versus Epidural Extended Release Morphine for Pediatric Patients Undergoing Spinal Fusion
NCT00958581	PHASE4	COMPLETED	Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
NCT01852747	PHASE4	TERMINATED	Comparison of Actifuse ABX and Local Bone in Spinal Surgery
NCT02464813	PHASE4	COMPLETED	Effect of Pregabalin on Immediate Post-operative and Longterm Pain
NCT02465099	PHASE4	TERMINATED	Posterior Spinal Fusion With Two Energy Dissection Techniques
NCT06540885	PHASE4	RECRUITING	A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
NCT06616220	PHASE4	COMPLETED	Dexamethasone for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06789016	PHASE4	COMPLETED	Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT00323752	PHASE3	COMPLETED	Recombinant Human Erythropoietin Compared to Autologous Pre-Donation Prior to Scoliosis Surgery in Children.
NCT00684112	PHASE3	COMPLETED	Analgesic Effects of Gabapentin After Scoliosis Surgery in Children
NCT00737997	PHASE3	COMPLETED	Effect of Early Morphine Administration on the Development of Acute Opioid Tolerance During Pediatric Scoliosis Surgery
NCT01103115	PHASE3	COMPLETED	Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS)
NCT01108211	PHASE3	COMPLETED	Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS)
NCT01205256	PHASE3	COMPLETED	IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction
NCT02558010	PHASE3	COMPLETED	Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients
NCT03537612	PHASE3	TERMINATED	Sensorial and Physiological Mechanism-based Assessments of Perioperative Pain
NCT00273598	PHASE2	COMPLETED	Comparing Two Instrumentation Systems for the Treatment of Adolescent Scoliosis
NCT01148888	PHASE2	COMPLETED	The Effect of Magnesium Sulfate on Motor and Somatosensory Evoked Potentials in Children Undergoing Scoliosis Surgery
NCT00154505	PHASE1	COMPLETED	Effects of Lateral Trunk Support on Spinal Alignment in Spinal Cord Injured Persons
NCT00155545	PHASE1	COMPLETED	Influence of Leg Length Discrepancy on the Spinal Shape and Biomechanics in Functional and Idiopathic Scoliosis Patients
NCT00671931	PHASE1	COMPLETED	Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine
NCT01677650	PHASE1	WITHDRAWN	Pharmacogenomics of Methadone in Spine Fusion Surgery
NCT00207857	Not specified	WITHDRAWN	Test-Retest Reliability of Pulmonary Function Tests in Patients With Duchenne’s Muscular Dystrophy
NCT00256672	Not specified	UNKNOWN	Effectiveness of Bracing in Preventing Scoliosis in Children With Spinal Cord Injury
NCT00320619	Not specified	COMPLETED	Epsilon-Aminocaproaic Acid to Reduce the Need for Blood Transfusions During and Following Spine Surgery
NCT00411060	Not specified	RECRUITING	Clinical Orthopaedic Data Bank (Acute and Chronic)
NCT00445393	Not specified	COMPLETED	Adolescent Idiopathic Scoliosis and Mental Health
NCT00577226	Not specified	TERMINATED	Shilla Growth Permitting Spinal Instrumentation System for Treatment of Scoliosis in the Immature Spine
NCT00680264	Not specified	UNKNOWN	Prospective Database Registry Study of Scoliosis in Children With Cerebral Palsy
NCT00726128	Not specified	COMPLETED	Patient Outcomes Evaluation of the EBI Vuelock™ Anterior Cervical Plate System
NCT00842218	Not specified	UNKNOWN	The Idiopathic Scoliosis and Its Treatment (Orthopaedic and Surgery): Effect of the Severity, the Orthosis and the Arthrodesis on the Gait
NCT00854828	Not specified	COMPLETED	A Multicenter Prospective Study of Quality of Life in Adult Scoliosis
NCT00890227	Not specified	COMPLETED	Incidence of Proximal Junctional Kyphosis (PJK) in Long Posterior Spinal Fusion: A Study Comparing Traditional Open Surgery to Minimally Invasive Percutaneous Technique at the Proximal Fusion Levels
NCT00958542	Not specified	SUSPENDED	Prospective Study of Cerebral Palsy Scoliosis
NCT00994656	Not specified	COMPLETED	Is Pleth Variability Index (PVI) a Surrogate for Pulse Pressure Variations (PPV) in Pediatric Spine Fusion (SF) Surgery?
NCT01087034	Not specified	COMPLETED	Bracing During Infantile Scoliosis: Airways Study
NCT01109082	Not specified	COMPLETED	Gait and Postural Stability Assessment in Children With Idiopathic Scoliosis Undergoing Posterior Spine Instrumentation