Fetal growth restriction

Summary

Fetal growth restriction (MONDO:0005030) is a disease with 21 cohort genes and 224 clinical trials. Top therapeutic interventions include aspirin, somatropin, and artenimol.

At a glance

• Cohort genes: 21
• ClinVar variants: 24
• Clinical trials: 224

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fetal growth restriction
Mondo ID	MONDO:0005030
EFO	EFO:0000495
MeSH	D005317
NCIT	C114875
SNOMED CT	22033007
UMLS	C0015934
MedGen	4693
Is cancer (heuristic)	no

Also known as: fetal Growth retardation · fetal growth retardation · fetal SGA · fetal small for gestational Age · fetus small for gestational Age · foetal Growth retardation · foetal growth retardation · foetal SGA · foetal small for gestational Age · foetus small for gestational Age · intrauterine Growth restriction · intrauterine Growth retardation · IUGR

Data availability: 24 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › female reproductive system disorder › uterine disorder › placenta disorder › fetal growth restriction

Related subtypes (7): placental abruption, oligohydramnios, placenta accreta, placenta praevia, placental insufficiency, placenta neoplasm, disorder of extraembryonic membrane

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

24 retrieved; paginated sample, class counts are floors:

9 pathogenic, 8 likely pathogenic, 4 uncertain significance, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1047904	GRCh37/hg19 2q11.1-11.2(chr2:96755045-98021592)	ANKRD39	Pathogenic	criteria provided, single submitter
4795219	NM_001098502.2(CHCHD4):c.5C>T (p.Ser2Phe)	CHCHD4	Pathogenic	no assertion criteria provided
374100	NM_001377.3(DYNC2H1):c.10461+1G>A	DYNC2H1	Pathogenic	criteria provided, single submitter
6503	NM_001377.3(DYNC2H1):c.9044A>G (p.Asp3015Gly)	DYNC2H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374024	NM_000153.4(GALC):c.850G>A (p.Gly284Ser)	GALC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280793	NM_018486.3(HDAC8):c.496C>T (p.Arg166Ter)	HDAC8	Pathogenic	criteria provided, multiple submitters, no conflicts
3238952	GRCh38/hg38 3q27.1-27.2(chr3:183020090-185760128)x1	LOC129938037	Pathogenic	criteria provided, single submitter
684729	NM_032793.5(MFSD2A):c.229-25_229-23del	MFSD2A	Pathogenic	no assertion criteria provided
223153	NM_018129.4(PNPO):c.674G>A (p.Arg225His)	PNPO	Pathogenic	criteria provided, multiple submitters, no conflicts
1047903	GRCh37/hg19 4p16.3(chr4:388344-3872380)	TMEM175	Pathogenic	criteria provided, single submitter
4795218	Single allele	WNT7A	Pathogenic	no assertion criteria provided
267881	46;XX;t(1;5)(p23;q15)dn		Likely pathogenic	criteria provided, single submitter
4073651	NM_006182.4(DDR2):c.2105C>T (p.Ser702Phe)	DDR2	Likely pathogenic	criteria provided, single submitter
997045	GRCh37/hg19 1q24.3(chr1:172050936-172181677)	DNM3OS	Likely pathogenic	criteria provided, single submitter
374023	NM_000153.4(GALC):c.196G>A (p.Ala66Thr)	GALC	Likely pathogenic	criteria provided, single submitter
523381	NM_000834.5(GRIN2B):c.2216T>G (p.Met739Arg)	GRIN2B	Likely pathogenic	criteria provided, single submitter
374171	NM_133433.4(NIPBL):c.1811_1812del (p.Lys603_Ser604insTer)	NIPBL	Likely pathogenic	criteria provided, single submitter
3233357	NM_001035006.5(RPL17):c.452del (p.Thr151fs)	RPL17	Likely pathogenic	criteria provided, single submitter
997055	GRCh37/hg19 3p26.3-26.1(chr3:73914-4356052)	TRNT1	Likely pathogenic	criteria provided, single submitter
982316	NM_004818.3(DDX23):c.1886T>G (p.Ile629Ser)	DDX23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
559502	GRCh37/hg19 2p23.3(chr2:24807000-25700000)x3	ADCY3	Uncertain significance	no assertion criteria provided
1706640	NM_032199.3(ARID5B):c.1302del (p.Asn434fs)	ARID5B	Uncertain significance	criteria provided, single submitter
559399	Single allele	C9orf163	Uncertain significance	no assertion criteria provided
812762	NM_018297.4(NGLY1):c.758G>T (p.Cys253Phe)	NGLY1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 20 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT7A	Orphanet:2854	Fuhrmann syndrome
WNT7A	Orphanet:2879	Phocomelia, Schinzel type
HDAC8	Orphanet:199	Cornelia de Lange syndrome
HDAC8	Orphanet:3459	Wilson-Turner syndrome
TRNT1	Orphanet:369861	Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome
NGLY1	Orphanet:404454	Alacrimia-choreoathetosis-liver dysfunction syndrome
MFSD2A	Orphanet:2512	Autosomal recessive primary microcephaly
DDR2	Orphanet:93358	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
PNPO	Orphanet:79096	Pyridoxamine-5-phosphate deficiency-developmental and epileptic encephalopathy
GALC	Orphanet:206436	Infantile Krabbe disease
GALC	Orphanet:206443	Late-infantile/juvenile Krabbe disease
GALC	Orphanet:206448	Adult Krabbe disease
GRIN2B	Orphanet:589547	GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder
GRIN2B	Orphanet:697160	Infantile epileptic spasms syndrome

Cohort genes → proteins

21 cohort genes, 20 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	21

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL17	HGNC:10307	ENSG00000265681	P18621	Large ribosomal subunit protein uL22	clinvar
RPL23	HGNC:10316	ENSG00000125691	P62829	Large ribosomal subunit protein uL14	clinvar
WNT7A	HGNC:12786	ENSG00000154764	O00755	Protein Wnt-7a	clinvar
HDAC8	HGNC:13315	ENSG00000147099	Q9BY41	Histone deacetylase 8	clinvar
TRNT1	HGNC:17341	ENSG00000072756	Q96Q11	CCA tRNA nucleotidyltransferase 1, mitochondrial	clinvar
DDX23	HGNC:17347	ENSG00000174243	Q9BUQ8	Probable ATP-dependent RNA helicase DDX23	clinvar
ARID5B	HGNC:17362	ENSG00000150347	Q14865	AT-rich interactive domain-containing protein 5B	clinvar
NGLY1	HGNC:17646	ENSG00000151092	Q96IV0	Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase	clinvar
ADCY3	HGNC:234	ENSG00000138031	O60266	Adenylate cyclase type 3	clinvar
MFSD2A	HGNC:25897	ENSG00000168389	Q8NA29	Sodium-dependent lysophosphatidylcholine symporter 1	clinvar
CHCHD4	HGNC:26467	ENSG00000163528	Q8N4Q1	Mitochondrial intermembrane space import and assembly protein 40	clinvar
C9orf163	HGNC:26718	ENSG00000196366	Q8N9P6	Uncharacterized protein C9orf163	clinvar
DDR2	HGNC:2731	ENSG00000162733	Q16832	Discoidin domain-containing receptor 2	clinvar
ANKRD39	HGNC:28640	ENSG00000213337	Q53RE8	Ankyrin repeat domain-containing protein 39	clinvar
TMEM175	HGNC:28709	ENSG00000127419	Q9BSA9	Endosomal/lysosomal proton channel TMEM175	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	clinvar
PNPO	HGNC:30260	ENSG00000108439	Q9NVS9	Pyridoxine-5’-phosphate oxidase	clinvar
GALC	HGNC:4115	ENSG00000054983	P54803	Galactocerebrosidase	clinvar
DNM3OS	HGNC:41228	ENSG00000230630		DNM3 opposite strand/antisense RNA	clinvar
GRIN2B	HGNC:4586	ENSG00000273079	Q13224	Glutamate receptor ionotropic, NMDA 2B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL17	Large ribosomal subunit protein uL22	Component of the large ribosomal subunit.
RPL23	Large ribosomal subunit protein uL14	Component of the large ribosomal subunit.
WNT7A	Protein Wnt-7a	Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.
HDAC8	Histone deacetylase 8	Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
TRNT1	CCA tRNA nucleotidyltransferase 1, mitochondrial	Nucleotidyltransferase that catalyzes the addition and repair of the essential 3’-terminal CCA sequence in tRNAs, which is necessary for the attachment of amino acids to the 3’ terminus of tRNA molecules, using CTP and ATP as substrates. t…
DDX23	Probable ATP-dependent RNA helicase DDX23	Involved in pre-mRNA splicing and its phosphorylated form (by SRPK2) is required for spliceosomal B complex formation.
ARID5B	AT-rich interactive domain-containing protein 5B	Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.
NGLY1	Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase	Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation.
ADCY3	Adenylate cyclase type 3	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
MFSD2A	Sodium-dependent lysophosphatidylcholine symporter 1	Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.
CHCHD4	Mitochondrial intermembrane space import and assembly protein 40	Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes.
DDR2	Discoidin domain-containing receptor 2	Tyrosine kinase involved in the regulation of tissues remodeling.
TMEM175	Endosomal/lysosomal proton channel TMEM175	Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
PNPO	Pyridoxine-5’-phosphate oxidase	Catalyzes the oxidation of either pyridoxine 5’-phosphate (PNP) or pyridoxamine 5’-phosphate (PMP) into pyridoxal 5’-phosphate (PLP).
GALC	Galactocerebrosidase	Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine.
GRIN2B	Glutamate receptor ionotropic, NMDA 2B	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).

Protein-family classification

Druggable: 7 · Difficult: 1 · Unknown: 13 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	5	2.9×	0.132
Transporter	1	3.7×	0.595
Other/Unknown	13	1.1×	0.616
Kinase	1	1.3×	0.672
Scaffold/PPI	1	0.8×	0.714

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL17	Other/Unknown	no		Ribosomal_uL22, Ribosomal_uL22_euk_arc, Ribosomal_uL22_CS
RPL23	Other/Unknown	no		Ribosomal_uL14, Ribosomal_uL14_CS, Ribosomal_uL14_sf
WNT7A	Other/Unknown	no		Wnt, Wnt7, Wnt_CS
HDAC8	Enzyme (other)	yes	3.5.1.98	HDACs, HDAC_I/II, Ureohydrolase_dom_sf
TRNT1	Enzyme (other)	yes	2.7.7.72	PolA_pol_head_dom, PolyA_RNA-bd, NT_sf
DDX23	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
ARID5B	Other/Unknown	no		ARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
NGLY1	Enzyme (other)	yes	3.5.1.52	Transglutaminase-like, Peptide_N_glycanase_PAW_dom, Galactose-bd-like_sf
ADCY3	Other/Unknown	no		A/G_cyclase, A/G_cyclase_CS, Nucleotide_cyclase
MFSD2A	Transporter	yes		MFS_trans_sf, MFS_2
CHCHD4	Other/Unknown	no		CHCH, CHCHD4
C9orf163	Other/Unknown	no
DDR2	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ANKRD39	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
TMEM175	Other/Unknown	no		TMEM175-like
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
PNPO	Enzyme (other)	yes	1.4.3.5	Pyridox_Oxase, Pyridox_Oxase_N, Split_barrel_FMN-bd
GALC	Enzyme (other)	yes	3.2.1.46	Glyco_hydro_59, Aldolase_TIM, GH_hydrolase_sf
DNM3OS	Other/Unknown	no
GRIN2B	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt

Expression context

Cohort genes with no expression data: 0.

19 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	21
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	3
right ovary	3
calcaneal tendon	3
cortical plate	2
adrenal tissue	2
colonic epithelium	2
endothelial cell	2
secondary oocyte	2
sural nerve	2
right lobe of liver	2
right uterine tube	2
bronchial epithelial cell	2
ovary	1
ganglionic eminence	1
endometrium epithelium	1
ventricular zone	1
left adrenal gland	1
oocyte	1
granulocyte	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL17	134	ubiquitous	marker	left ovary, ovary, right ovary
RPL23	210	ubiquitous	marker	ganglionic eminence, left ovary, right ovary
WNT7A	96	broad	yes	cortical plate, endometrium epithelium, ventricular zone
HDAC8	244	ubiquitous	marker	colonic epithelium, adrenal tissue, left adrenal gland
TRNT1	254	ubiquitous	marker	endothelial cell, secondary oocyte, oocyte
DDX23	296	ubiquitous	marker	calcaneal tendon, sural nerve, granulocyte
ARID5B	299	ubiquitous	marker	type B pancreatic cell, saphenous vein, pericardium
NGLY1	290	ubiquitous	marker	sperm, male germ cell, right testis
ADCY3	281	broad	marker	tibial nerve, right ovary, sural nerve
MFSD2A	220	ubiquitous	marker	right lobe of liver, skin of abdomen, ileal mucosa
CHCHD4	254	ubiquitous	marker	left ventricle myocardium, endothelial cell, cardiac muscle of right atrium
C9orf163	121	tissue_specific	yes	right uterine tube, myocardium, pituitary gland
DDR2	270	ubiquitous	marker	cauda epididymis, tendon of biceps brachii, vena cava
ANKRD39	209	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
TMEM175	223	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
DYNC2H1	230	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, right uterine tube
PNPO	230	ubiquitous	marker	right lobe of liver, liver, kidney epithelium
GALC	295	ubiquitous	marker	adrenal tissue, bronchial epithelial cell, jejunal mucosa
DNM3OS	190	broad	marker	calcaneal tendon, left ovary, tendon
GRIN2B	138	broad	marker	buccal mucosa cell, cortical plate, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL17	5,372
DDX23	4,764
GRIN2B	3,611
NIPBL	3,278
HDAC8	3,087
TRNT1	2,982
ADCY3	1,965
DYNC2H1	1,885
WNT7A	1,809
ARID5B	1,778

Intra-cohort edges

A	B	Sources
HDAC8	NIPBL	string_interaction

Structural data

PDB: 16 · AlphaFold-only: 4 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL17	P18621	195
RPL23	P62829	190
HDAC8	Q9BY41	53
GRIN2B	Q13224	36
DDX23	Q9BUQ8	24
TMEM175	Q9BSA9	18
PNPO	Q9NVS9	6
DDR2	Q16832	5
CHCHD4	Q8N4Q1	4
DYNC2H1	Q8NCM8	4
WNT7A	O00755	3
TRNT1	Q96Q11	3
NIPBL	Q6KC79	3
ARID5B	Q14865	2
NGLY1	Q96IV0	2
MFSD2A	Q8NA29	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GALC	P54803	94.56
ANKRD39	Q53RE8	84.41
ADCY3	O60266	76.86
C9orf163	Q8N9P6	33.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 102. Enrichment computed across 21 evidence-associated genes (17 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Vitamin B6 activation to pyridoxal phosphate	1	223.9×	0.073	PNPO
tRNA processing in the mitochondrion	1	134.3×	0.073	TRNT1
Activated NTRK2 signals through FYN	1	112.0×	0.073	GRIN2B
Hedgehog ‘off’ state	2	21.0×	0.073	ADCY3, DYNC2H1
Peptide chain elongation	2	14.9×	0.073	RPL17, RPL23
Viral mRNA Translation	2	14.9×	0.073	RPL17, RPL23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	2	14.8×	0.073	RPL17, RPL23
Selenocysteine synthesis	2	14.1×	0.073	RPL17, RPL23
Eukaryotic Translation Termination	2	14.1×	0.073	RPL17, RPL23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2	13.8×	0.073	RPL17, RPL23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	2	13.8×	0.073	RPL17, RPL23
Formation of a pool of free 40S subunits	2	13.2×	0.073	RPL17, RPL23
Response of EIF2AK4 (GCN2) to amino acid deficiency	2	13.0×	0.073	RPL17, RPL23
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	2	12.6×	0.073	RPL17, RPL23
L13a-mediated translational silencing of Ceruloplasmin expression	2	11.9×	0.073	RPL17, RPL23
SRP-dependent cotranslational protein targeting to membrane	2	11.8×	0.073	RPL17, RPL23
GTP hydrolysis and joining of the 60S ribosomal subunit	2	11.8×	0.073	RPL17, RPL23
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2	11.5×	0.073	RPL17, RPL23
Adenylate cyclase activating pathway	1	67.2×	0.075	ADCY3
Cohesin Loading onto Chromatin	1	67.2×	0.075	NIPBL
Adenylate cyclase inhibitory pathway	1	44.8×	0.095	ADCY3
PKA activation in glucagon signalling	1	39.5×	0.095	ADCY3
PKA activation	1	37.3×	0.095	ADCY3
MECP2 regulates neuronal receptors and channels	1	35.4×	0.095	GRIN2B
Activation of GABAB receptors	1	35.4×	0.095	ADCY3
PKA-mediated phosphorylation of CREB	1	33.6×	0.095	ADCY3
Ras activation upon Ca2+ influx through NMDA receptor	1	33.6×	0.095	GRIN2B
Unblocking of NMDA receptors, glutamate binding and activation	1	32.0×	0.095	GRIN2B
Synaptic adhesion-like molecules	1	32.0×	0.095	GRIN2B
Negative regulation of NMDA receptor-mediated neuronal transmission	1	32.0×	0.095	GRIN2B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
uterus morphogenesis	2	312.1×	0.004	WNT7A, NIPBL
establishment of blood-brain barrier	2	156.0×	0.009	WNT7A, MFSD2A
mitotic sister chromatid cohesion	2	124.8×	0.010	HDAC8, NIPBL
tRNA 3’-terminal CCA addition	1	936.2×	0.017	TRNT1
external genitalia morphogenesis	1	936.2×	0.017	NIPBL
pyridoxal 5’-phosphate biosynthetic process	1	936.2×	0.017	PNPO
asymmetric protein localization involved in cell fate determination	1	936.2×	0.017	WNT7A
tRNA surveillance	1	936.2×	0.017	TRNT1
lysophospholipid translocation	1	936.2×	0.017	MFSD2A
regulation of phosphatidylethanolamine metabolic process	1	936.2×	0.017	MFSD2A
obsolete regulation of phosphatidylserine metabolic process	1	936.2×	0.017	MFSD2A
obsolete positive regulation of DNA-binding transcription factor activity	2	66.9×	0.017	ARID5B, DDR2
positive regulation of excitatory postsynaptic potential	2	58.5×	0.017	WNT7A, GRIN2B
embryonic forelimb morphogenesis	2	55.1×	0.017	WNT7A, NIPBL
face morphogenesis	2	55.1×	0.017	ARID5B, NIPBL
dorsal/ventral pattern formation	2	46.8×	0.017	WNT7A, DYNC2H1
cis assembly of pre-catalytic spliceosome	1	468.1×	0.019	DDX23
galactosylceramide catabolic process	1	468.1×	0.019	GALC
olfactory learning	1	468.1×	0.019	ADCY3
pyridoxine biosynthetic process	1	468.1×	0.019	PNPO
pyridoxamine metabolic process	1	468.1×	0.019	PNPO
regulation of developmental growth	1	468.1×	0.019	NIPBL
gallbladder development	1	468.1×	0.019	NIPBL
postsynapse assembly	1	468.1×	0.019	WNT7A
regulation of phosphatidylcholine metabolic process	1	468.1×	0.019	MFSD2A
positive regulation of protein localization to presynapse	1	468.1×	0.019	WNT7A
cognition	2	31.7×	0.019	MFSD2A, NIPBL
cellular response to transforming growth factor beta stimulus	2	30.7×	0.019	WNT7A, DDR2
brain development	3	13.2×	0.019	MFSD2A, NIPBL, GRIN2B
somatic stem cell population maintenance	2	27.5×	0.020	WNT7A, NIPBL

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aspirin	Phase 3 (in late-stage trials)
Dinoprostone	Phase 3 (in late-stage trials)
Enoxaparin Sodium	Phase 3 (in late-stage trials)
Glutamine	Phase 3 (in late-stage trials)
Heparin	Phase 3 (in late-stage trials)
Somatropin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Sildenafil.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 15

Druggability breadth: 9 of 21 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPL17	GENTAMICIN SULFATE
RPL23	GENTAMICIN SULFATE
HDAC8	CELECOXIB
NGLY1	DACTINOMYCIN
DDR2	PONATINIB
GRIN2B	HALOPERIDOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDR2	59	4
HDAC8	37	4
GRIN2B	35	4
RPL17	1	4
RPL23	1	4
NGLY1	1	4
WNT7A	0	0
TRNT1	0	0
DDX23	0	0
ARID5B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL17, RPL23
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8
BELINOSTAT	4	HDAC8
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
DACTINOMYCIN	4	DDR2, NGLY1
PONATINIB	4	DDR2
FEDRATINIB	4	DDR2
TIVOZANIB	4	DDR2
LENVATINIB	4	DDR2
AXITINIB	4	DDR2
SORAFENIB	4	DDR2
DASATINIB ANHYDROUS	4	DDR2
REGORAFENIB	4	DDR2
CABOZANTINIB	4	DDR2
VANDETANIB	4	DDR2
NILOTINIB	4	DDR2
BOSUTINIB	4	DDR2
TOVORAFENIB	4	DDR2
PAZOPANIB	4	DDR2
NINTEDANIB	4	DDR2
SUNITINIB	4	DDR2
DASATINIB	4	DDR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HDAC8	2,631	Binding:2599, ADMET:25, Functional:6, Toxicity:1
GRIN2B	471	Binding:429, Functional:36, ADMET:5, Toxicity:1
DDR2	389	Binding:386, ADMET:3
RPL17	90	Binding:90
RPL23	90	Binding:90
ADCY3	17	Binding:15, Functional:2
NGLY1	9	Binding:9
GALC	3	Binding:2, Functional:1
PNPO	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC8	3.5.1.98	histone deacetylase
TRNT1	2.7.7.72	CCA tRNA nucleotidyltransferase
NGLY1	3.5.1.52	peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase
DDR2	2.7.10.1	receptor protein-tyrosine kinase
PNPO	1.4.3.5	pyridoxal 5’-phosphate synthase
GALC	3.2.1.46	galactosylceramidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HDAC8	2,631
DDR2	389
GRIN2B	471

Pharmacogenomics

Cohort genes with a PharmGKB record: 20; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPL17, RPL23
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8
BELINOSTAT	4	HDAC8
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
DACTINOMYCIN	4	DDR2, NGLY1
PONATINIB	4	DDR2
FEDRATINIB	4	DDR2
TIVOZANIB	4	DDR2
LENVATINIB	4	DDR2
AXITINIB	4	DDR2
SORAFENIB	4	DDR2
DASATINIB ANHYDROUS	4	DDR2
REGORAFENIB	4	DDR2
CABOZANTINIB	4	DDR2
VANDETANIB	4	DDR2
NILOTINIB	4	DDR2
BOSUTINIB	4	DDR2
TOVORAFENIB	4	DDR2
PAZOPANIB	4	DDR2
NINTEDANIB	4	DDR2
SUNITINIB	4	DDR2
DASATINIB	4	DDR2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	RPL17, RPL23, HDAC8, NGLY1, DDR2, GRIN2B
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	TRNT1, MFSD2A, PNPO
D	Druggable family + AlphaFold only, no drug	1	GALC
E	Difficult family or no structure, no drug	11	WNT7A, DDX23, ARID5B, ADCY3, CHCHD4, C9orf163, ANKRD39, TMEM175, NIPBL, DYNC2H1 (+1 more)

Undrugged target profiles

15 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
WNT7A	0	—
TRNT1	0	—
DDX23	0	—
ARID5B	0	—
ADCY3	17	—
MFSD2A	0	—
CHCHD4	0	—
C9orf163	0	—
ANKRD39	0	—
TMEM175	0	—
NIPBL	0	—
DYNC2H1	0	—
PNPO	2	—
GALC	3	—
DNM3OS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 224.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	181
PHASE3	19
PHASE4	10
PHASE2	5
PHASE2/PHASE3	4
PHASE1	3
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07171086	PHASE4	NOT_YET_RECRUITING	AI-POCUS for Maternal and Neonatal Health in Ethiopia
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01390051	PHASE4	COMPLETED	Can Low Molecular Weight Heparin During Pregnancy With Intrauterine Growth Restriction Increase Birth Weight?
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT05029778	PHASE4	UNKNOWN	Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
NCT05800938	PHASE4	COMPLETED	The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT04762992	PHASE3	ENROLLING_BY_INVITATION	LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
NCT05651347	PHASE3	RECRUITING	Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT06497959	PHASE3	RECRUITING	Study of Placental Vascularization Using Contrast Ultrasound
NCT00174252	PHASE3	COMPLETED	Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
NCT00197340	PHASE3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00452491	PHASE3	COMPLETED	MAXOMAT ® in the Treatment of Severe Early Onset Intrauterine Growth Retardation on Pre-pubertal Children
NCT01073605	PHASE3	COMPLETED	Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation
NCT01107782	PHASE2/PHASE3	UNKNOWN	Sildenafil and Uteroplacental Perfusion
NCT02277132	PHASE2/PHASE3	TERMINATED	The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
NCT02336243	PHASE3	UNKNOWN	A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders
NCT02442492	PHASE2/PHASE3	TERMINATED	Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction
NCT02523222	PHASE2/PHASE3	COMPLETED	Dextrose Gel Does Not Prevent Neonatal Hypoglycemia
NCT02590536	PHASE3	COMPLETED	A Trial Evaluating the Role of Sildenafil in the Treatment of Fetal Growth Restriction
NCT02672566	PHASE3	COMPLETED	Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
NCT03177824	PHASE3	UNKNOWN	Sildenafil Citrate for Treatment of Growth-restricted Fetuses
NCT03230162	PHASE3	UNKNOWN	Sildenafil Versus Low Molecular Weight Heparin in Fetal Growth Restriction Treatment
NCT03324139	PHASE3	COMPLETED	Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.
NCT03669185	PHASE3	UNKNOWN	Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
NCT04084990	PHASE3	TERMINATED	Sleep Apnea and Fetal Growth Restriction
NCT04557475	PHASE3	WITHDRAWN	Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction
NCT05253781	PHASE3	COMPLETED	Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
NCT05774236	PHASE3	COMPLETED	Cook´s Balloon Versus Dinoprostone for Labor Induction of Term Pregnancies With Fetal Growth Restriction
NCT07098975	PHASE2	RECRUITING	Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)
NCT02280031	PHASE2	COMPLETED	Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial.
NCT02425436	PHASE2	COMPLETED	Role of Ginkgo Biloba Extract in IUGR
NCT02678221	PHASE2	UNKNOWN	Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction
NCT02696577	PHASE2	COMPLETED	The Effect of Omega 3 on Pregnancy Complicated by Asymmetrical Intrauterine Growth Restriction
NCT07549295	PHASE1	ENROLLING_BY_INVITATION	Melatonin and Perinatal Outcomes in MVM-Related Fetal Growth Restriction (MIMVMFGR)
NCT04508751	PHASE1	COMPLETED	PED NEONAT 20-000599 Fetal Body Composition

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	7
SOMATROPIN	4	3
ARTENIMOL	4	1
DINOPROSTONE	4	1
FERUMOXYTOL	4	1
GINKGO	4	1
MELATONIN	4	1
PRAVASTATIN	4	1
SULFUR HEXAFLUORIDE	4	1
TINZAPARIN SODIUM	4	1
ACESULFAME	3	1
ARGININE	3	1
DOCONEXENT	3	1
L-CITRULLINE	3	1
PENTAERYTHRITOL TETRANITRATE	3	1
TINZAPARIN	3	1
D-MANNOSE	2	1
CHEMBL4792718	0	2
CHEMBL5439651	0	2
CHEMBL365590	0	1