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Atlas / Disease / Preterm premature rupture of the membranes

Preterm premature rupture of the membranes

disease
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Also known as PPROMpreterm premature rupture of the membranes, susceptibility to

Summary

Preterm premature rupture of the membranes (MONDO:0012511) is a disease with 22 cohort genes (18 GWAS associations across 7 studies) and 17 clinical trials. The dominant Reactome pathway is Extracellular matrix organization (4 cohort genes). Top therapeutic interventions include cefazolin, clarithromycin, and erythromycin.

At a glance

  • Cohort genes: 22
  • GWAS associations: 18
  • ClinVar variants: 5
  • Clinical trials: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepreterm premature rupture of the membranes
Mondo IDMONDO:0012511
MeSHC563032
OMIM610504
DOIDDOID:0111144
NCITC92862
SNOMED CT312974005
UMLSC0729264
MedGen147582
Is cancer (heuristic)no

Also known as: PPROM · preterm premature rupture of the membranes · preterm premature rupture of the membranes, susceptibility to

Data availability: 5 ClinVar variants · 18 GWAS associations (7 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › female reproductive system disorder › preterm premature rupture of the membranes

Related subtypes (33): ectopic pregnancy, pelvic inflammatory disease, endosalpingiosis, vaginal disorder, prolapse of female genital organ, Allen-Masters syndrome, fallopian tube disorder, vulvar disease, uterine disorder, gynatresia, Bartholin duct cyst, ovarian disorder, hymen, imperforate, mammary-digital-nail syndrome, Asherman syndrome, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, polycystic ovaries-urethral sphincter dysfunction syndrome, granulomatous mastitis, vaginal atresia, mullerian aplasia, vulvovaginal gingival syndrome, isolated partial vaginal agenesis, female infertility, female reproductive system neoplasm, polyp of vulva, vulval varices, vulvodynia, menstrual cycle-dependent periodic fever, Bartholin’s gland disease, delayed puberty, self-limited, menstrual disorder

Genetics & variants

GWAS landscape

18 GWAS associations across 7 studies. Top hits map to 14 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1170236424e-07LINC02153?5.85
rs117883876e-07TLE1-DT - RNA5SP287?2.96
rs6428462e-06KSR2?1.94
rs49191052e-06UBTD1?2.02
rs2016084722e-06SUCLG2?2.15
rs177667563e-06RNF217-AS1, NKAIN2?3.78
rs342888364e-06GALNT3?2.52
rs2020130484e-06FSTL5 - MTHFD2P4?3.78
rs26165544e-06VGLL4?1.95
rs127656645e-06ADAMTS14?2.94
rs75374595e-06LINC01739?2.7
rs65903905e-06RPS27P20 - LINC01395?2.13
rs72314066e-06FHOD3?2.3
rs1181127627e-06FNDC3A?3.25
rs618878357e-06LGR4?4.7
rs28078207e-06MIR3171HG - BNIP3P1?1.96
rs1130189218e-06MSI2?2.82
rs47049168e-06MARK2P11 - LINC02227?2.13

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90727197Kim HI20262,75041,276Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90474237UK Biobank Whole-Genome Sequencing Consortium20251,196457,244Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080718Backman JD20211,136210,861Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084704Backman JD20211,136210,861Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080717Backman JD2021566211,437Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084703Backman JD2021566211,437Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST008180Tiensuu H20191330Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic18

MAF distribution

BucketVariants
common (>=0.05)17
low_freq (0.01-0.05)0
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant13
intergenic_variant5

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs117023642820981609C>G0.05intron_variantLINC021534e-07Tier 4: intronic/intergenic
rs11788387981855961G>T0.05intergenic_variantTLE1-DT - RNA5SP2876e-07Tier 4: intronic/intergenic
rs64284612117674581G>A,C0.05intron_variantKSR22e-06Tier 4: intronic/intergenic
rs49191051097520476A>G,T0.05intron_variantUBTD12e-06Tier 4: intronic/intergenic
rs201608472367394450intron_variantSUCLG22e-06Tier 4: intronic/intergenic
rs177667566124704154A>G0.05intron_variantRNF217-AS1, NKAIN23e-06Tier 4: intronic/intergenic
rs342888362165809595G>A0.05intron_variantGALNT34e-06Tier 4: intronic/intergenic
rs2020130484162241645GA>G0.05intergenic_variantFSTL5 - MTHFD2P44e-06Tier 4: intronic/intergenic
rs2616554311623075C>A,G,T0.05intron_variantVGLL44e-06Tier 4: intronic/intergenic
rs127656641070735022G>A0.05intron_variantADAMTS145e-06Tier 4: intronic/intergenic
rs7537459163068264T>A,C0.05intron_variantLINC017395e-06Tier 4: intronic/intergenic
rs659039011129540086G>A0.05intergenic_variantRPS27P20 - LINC013955e-06Tier 4: intronic/intergenic
rs72314061836644496G>A0.05intron_variantFHOD36e-06Tier 4: intronic/intergenic
rs1181127621349071567A>G0.05intron_variantFNDC3A7e-06Tier 4: intronic/intergenic
rs618878351127409619T>C0.05intron_variantLGR47e-06Tier 4: intronic/intergenic
rs28078201428028365G>A0.05intergenic_variantMIR3171HG - BNIP3P17e-06Tier 4: intronic/intergenic
rs1130189211757647536C>G0.05intron_variantMSI28e-06Tier 4: intronic/intergenic
rs47049165158104961G>A0.05intergenic_variantMARK2P11 - LINC022278e-06Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 benign

ClinVarVariant (HGVS)GeneClassificationReview
17113MMP8, HAPLOTYPE, TGGMMP8Pathogenicno assertion criteria provided
8664NC_000011.10:g.75561608C>TSERPINH1Pathogenicno assertion criteria provided
195143NM_001235.5(SERPINH1):c.580C>A (p.Arg194Ser)SERPINH1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
3574000NM_001235.5(SERPINH1):c.715C>T (p.Arg239Trp)SERPINH1Uncertain significancecriteria provided, multiple submitters, no conflicts
802715NM_002421.4(MMP1):c.105+115delMMP1Benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SERPINH1Orphanet:216812Osteogenesis imperfecta type 3
GALNT3Orphanet:306661Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome
MMP1Orphanet:79408Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form

Cohort genes → proteins

22 cohort genes, 20 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only19
multi_evidence3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SUCLG2HGNC:11450ENSG00000172340Q96I99Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrialgwas
LGR4HGNC:13299ENSG00000205213Q9BXB1Leucine-rich repeat-containing G-protein coupled receptor 4gwas
MMS19HGNC:13824ENSG00000155229Q96T76MMS19 nucleotide excision repair protein homologgwas
ADAMTS14HGNC:14899ENSG00000138316Q8WXS8A disintegrin and metalloproteinase with thrombospondin motifs 14gwas
SERPINH1HGNC:1546ENSG00000149257P50454Serpin H1clinvar
NKAIN2HGNC:16443ENSG00000188580Q5VXU1Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2gwas
EXOSC1HGNC:17286ENSG00000171311Q9Y3B2Exosome complex component CSL4gwas
KSR2HGNC:18610ENSG00000171435Q6VAB6Kinase suppressor of Ras 2gwas
FNDC3AHGNC:20296ENSG00000102531Q9Y2H6Fibronectin type-III domain-containing protein 3Agwas
ZDHHC16HGNC:20714ENSG00000171307Q969W1Palmitoyltransferase ZDHHC16gwas
FSTL5HGNC:21386ENSG00000168843Q8N475Follistatin-related protein 5gwas
TMEM45BHGNC:25194ENSG00000151715Q96B21Transmembrane protein 45Bgwas
FHOD3HGNC:26178ENSG00000134775Q2V2M9FH1/FH2 domain-containing protein 3gwas
LINC00466HGNC:27294ENSG00000224209long intergenic non-protein coding RNA 466gwas
VGLL4HGNC:28966ENSG00000144560Q14135Transcription cofactor vestigial-like protein 4gwas
SPATA31D4HGNC:38601ENSG00000189357Q6ZUB0Spermatogenesis-associated protein 31D4gwas
GALNT3HGNC:4125ENSG00000115339Q14435Polypeptide N-acetylgalactosaminyltransferase 3gwas
LINC00645HGNC:44299ENSG00000258548long intergenic non-protein coding RNA 645gwas
MMP1HGNC:7155ENSG00000196611P03956Interstitial collagenaseclinvar
MMP8HGNC:7175ENSG00000118113P22894Neutrophil collagenaseclinvar
MSI1HGNC:7330ENSG00000135097O43347RNA-binding protein Musashi homolog 1gwas
BARX2HGNC:956ENSG00000043039Q9UMQ3Homeobox protein BarH-like 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SUCLG2Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrialGTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA.
LGR4Leucine-rich repeat-containing G-protein coupled receptor 4Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs.
MMS19MMS19 nucleotide excision repair protein homologKey component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity.
ADAMTS14A disintegrin and metalloproteinase with thrombospondin motifs 14Has aminoprocollagen type I processing activity in the absence of ADAMTS2.
SERPINH1Serpin H1Binds specifically to collagen.
EXOSC1Exosome complex component CSL4Non-catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.
KSR2Kinase suppressor of Ras 2Location-regulated scaffold connecting MEK to RAF.
FNDC3AFibronectin type-III domain-containing protein 3AMediates spermatid-Sertoli adhesion during spermatogenesis.
ZDHHC16Palmitoyltransferase ZDHHC16Palmitoyl acyltransferase that mediates palmitoylation of proteins such as PLN and ZDHHC6.
TMEM45BTransmembrane protein 45BPlays a role in innate immunity.
FHOD3FH1/FH2 domain-containing protein 3Actin-organizing protein that may cause stress fiber formation together with cell elongation.
VGLL4Transcription cofactor vestigial-like protein 4May act as a specific coactivator for the mammalian TEFs.
SPATA31D4Spermatogenesis-associated protein 31D4May play a role in spermatogenesis.
GALNT3Polypeptide N-acetylgalactosaminyltransferase 3Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
MMP1Interstitial collagenaseCleaves collagens of types I, II, and III at one site in the helical domain.
MMP8Neutrophil collagenaseCan degrade fibrillar type I, II, and III collagens.
MSI1RNA-binding protein Musashi homolog 1RNA binding protein that regulates the expression of target mRNAs at the translation level.
BARX2Homeobox protein BarH-like 2Transcription factor.

Protein-family classification

Druggable: 10 · Difficult: 1 · Unknown: 11 · Druggable fraction: 0.45

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.

FamilyGenesFoldFDR
Protease35.0×0.148
Antibody/Immunoglobulin22.6×0.606
Enzyme (other)31.6×0.645
Kinase11.3×0.853
GPCR11.1×0.853
Other/Unknown110.9×0.908
Transcription factor10.4×0.942

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SUCLG2Enzyme (other)yes6.2.1.4Succ_CoA_ligase-like_bsu, SUCC_ACL_C, ATP-grasp_succ-CoA_synth-type
LGR4GPCRyesGPCR_Rhodpsn, LRRNT, Leu-rich_rpt
MMS19Other/UnknownnoARM-like, ARM-type_fold, MMS19_C
ADAMTS14Proteaseyes3.4.24.14TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
SERPINH1Other/UnknownnoSerpin_fam, Serpin_CS, Serpin_dom
NKAIN2Other/UnknownnoNa/K-Atpase_Interacting
EXOSC1Other/UnknownnoS1_domain, NA-bd_OB-fold, EXOSC1_C
KSR2Kinaseyes2.7.11.25Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
FNDC3AAntibody/ImmunoglobulinyesFN3_dom, Ig-like_fold, FN3_sf
ZDHHC16Enzyme (other)yes2.3.1.225Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
FSTL5Antibody/ImmunoglobulinyesEF_hand_dom, Kazal_dom, Ig_sub2
TMEM45BOther/UnknownnoDUF716, TMEM45
FHOD3Other/UnknownnoARM-like, DAD_dom, GBD/FH3_dom
LINC00466Other/Unknownno
VGLL4Other/UnknownnoTDU_repeat, VGLL4
SPATA31D4Other/UnknownnoSPATA31-like, SPATA31
GALNT3Enzyme (other)yes2.4.1.41Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
LINC00645Other/Unknownno
MMP1Proteaseyes3.4.24.7Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like
MMP8Proteaseyes3.4.24.34Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like
MSI1Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, MSI_RRM2
BARX2Transcription factornoHTH_motif, HD, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)1
broad (>20)21
unknown0

Top tissues across cohort

TissueCohort genes
stromal cell of endometrium3
male germ line stem cell (sensu Vertebrata) in testis3
mucosa of sigmoid colon2
adrenal tissue2
body of pancreas2
mucosa of transverse colon2
pancreatic ductal cell2
parotid gland2
ventricular zone2
left testis2
right testis2
bone marrow cell2
colonic mucosa1
rectum1
hair follicle1
cerebellar cortex1
cerebellar hemisphere1
right hemisphere of cerebellum1
gall bladder1
vena cava1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SUCLG2286ubiquitousmarkercolonic mucosa, mucosa of sigmoid colon, rectum
LGR4280ubiquitousmarkeradrenal tissue, body of pancreas, hair follicle
MMS19286ubiquitousmarkerright hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ADAMTS14156broadyesgall bladder, vena cava, mucosa of transverse colon
SERPINH1265ubiquitousmarkerstromal cell of endometrium, endometrium epithelium, smooth muscle tissue
NKAIN2178broadmarkerC1 segment of cervical spinal cord, spinal cord, corpus callosum
EXOSC1254ubiquitousmarkergranulocyte, stromal cell of endometrium, body of pancreas
KSR2114broadmarkerBrodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
FNDC3A291ubiquitousmarkercorpus epididymis, caput epididymis, adrenal tissue
ZDHHC16255ubiquitousmarkerpancreatic ductal cell, parotid gland, stromal cell of endometrium
FSTL5126broadmarkercerebellar vermis, endothelial cell, pons
TMEM45B196broadmarkerileal mucosa, jejunal mucosa, mucosa of transverse colon
FHOD3244ubiquitousmarkerapex of heart, left ventricle myocardium, ventricular zone
LINC00466133tissue_specificmarkerright testis, left testis, male germ line stem cell (sensu Vertebrata) in testis
VGLL4299ubiquitousmarkertibia, nipple, trigeminal ganglion
SPATA31D46yesmale germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
GALNT3234ubiquitousmarkermucosa of sigmoid colon, bronchial epithelial cell, parotid gland
LINC00645102tissue_specificmarkerpigmented layer of retina, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis
MMP1172broadmarkerepithelial cell of pancreas, pancreatic ductal cell, islet of Langerhans
MMP8138tissue_specificmarkertrabecular bone tissue, bone marrow, bone marrow cell
MSI1164broadmarkerventricular zone, ganglionic eminence, Brodmann (1909) area 10
BARX2154broadmarkerlower esophagus mucosa, esophagus mucosa, minor salivary gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SUCLG26,231
MMP12,933
LGR42,525
EXOSC12,506
MMS192,359
MSI11,813
FNDC3A1,792
MMP81,684
FSTL51,547
NKAIN21,271

Intra-cohort edges

ABSources
MMP1MMP8biogrid_interaction

Structural data

PDB: 8 · AlphaFold-only: 12 · No structure: 2

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
MMP8P2289425
LGR4Q9BXB123
MMP1P0395615
KSR2Q6VAB69
EXOSC1Q9Y3B28
SUCLG2Q96I996
FNDC3AQ9Y2H66
VGLL4Q141351

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SERPINH1P5045491.71
MMS19Q96T7691.00
TMEM45BQ96B2190.90
GALNT3Q1443589.88
ZDHHC16Q969W187.96
FSTL5Q8N47583.57
NKAIN2Q5VXU176.15
ADAMTS14Q8WXS870.22
BARX2Q9UMQ365.88
MSI1O4334765.76
FHOD3Q2V2M964.62
SPATA31D4Q6ZUB045.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 66. Enrichment computed across 22 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Extracellular matrix organization422.9×0.001ADAMTS14, SERPINH1, MMP1, MMP8
Collagen formation283.0×0.008ADAMTS14, SERPINH1
Activation of Matrix Metalloproteinases256.1×0.012MMP1, MMP8
Collagen degradation231.9×0.024MMP1, MMP8
Collagen biosynthesis and modifying enzymes231.0×0.024ADAMTS14, SERPINH1
Degradation of the extracellular matrix221.4×0.041MMP1, MMP8
FGFR3c ligand binding and activation179.9×0.087GALNT3
Cytosolic iron-sulfur cluster assembly169.2×0.087MMS19
mRNA decay by 3’ to 5’ exoribonuclease164.9×0.087EXOSC1
Defective GALNT3 causes HFTC164.9×0.087GALNT3
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA157.7×0.087EXOSC1
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA157.7×0.087EXOSC1
KSRP (KHSRP) binds and destabilizes mRNA157.7×0.087EXOSC1
Regulation of FZD by ubiquitination147.2×0.092LGR4
Basigin interactions139.9×0.092MMP1
Signaling by RAS mutants138.5×0.092KSR2
Citric acid cycle (TCA cycle)138.5×0.092SUCLG2
Attenuation phase137.1×0.092SERPINH1
ATF4 activates genes in response to endoplasmic reticulum stress137.1×0.092EXOSC1
HSF1 activation134.6×0.092SERPINH1
HSF1-dependent transactivation128.8×0.092SERPINH1
Signaling by high-kinase activity BRAF mutants128.8×0.092KSR2
Defective B3GALTL causes PpS128.1×0.092ADAMTS14
Nuclear RNA decay128.1×0.092EXOSC1
O-glycosylation of TSR domain-containing proteins127.3×0.092ADAMTS14
MAP2K and MAPK activation125.9×0.092KSR2
Signaling by RAF1 mutants125.3×0.092KSR2
Signaling by moderate kinase activity BRAF mutants123.1×0.092KSR2
Paradoxical activation of RAF signaling by kinase inactive BRAF123.1×0.092KSR2
Signaling downstream of RAS mutants123.1×0.092KSR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
collagen catabolic process358.8×0.002ADAMTS14, MMP1, MMP8
extracellular matrix organization318.3×0.027ADAMTS14, MMP1, MMP8
fibroblast growth factor receptor signaling pathway involved in forebrain neuron fate commitment1842.6×0.032ZDHHC16
extracellular matrix disassembly236.6×0.032MMP1, MMP8
chondrocyte development involved in endochondral bone morphogenesis1421.3×0.038SERPINH1
metanephric glomerulus development1421.3×0.038LGR4
polysaccharide metabolic process1280.9×0.038GALNT3
metanephric nephron tubule morphogenesis1280.9×0.038LGR4
collagen fibril organization222.5×0.038ADAMTS14, SERPINH1
succinyl-CoA metabolic process1168.5×0.047SUCLG2
succinate metabolic process1168.5×0.047SUCLG2
epithelial cell proliferation involved in renal tubule morphogenesis1168.5×0.047LGR4
protein maturation216.4×0.048MMS19, SERPINH1
intestinal stem cell homeostasis1120.4×0.053LGR4
succinyl-CoA catabolic process1120.4×0.053SUCLG2
myotube differentiation1105.3×0.053BARX2
positive regulation of microglial cell activation1105.3×0.053MMP8
negative regulation of cardiac muscle cell proliferation193.6×0.057VGLL4
cellular response to UV-A170.2×0.065MMP1
cardiac myofibril assembly164.8×0.065FHOD3
regulation of BMP signaling pathway160.2×0.065FSTL5
positive regulation of neuroinflammatory response160.2×0.065MMP8
Sertoli cell development156.2×0.065FNDC3A
collagen biosynthetic process152.7×0.065SERPINH1
positive regulation of tumor necrosis factor-mediated signaling pathway152.7×0.065MMP8
telencephalon development149.6×0.065ZDHHC16
regulation of sodium ion transport146.8×0.065NKAIN2
chondrocyte development146.8×0.065GALNT3
bone remodeling146.8×0.065LGR4
male genitalia development144.4×0.065LGR4

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 20

Druggability breadth: 8 of 22 evidence-associated genes (36%) 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.

SymbolExample approved molecule
MMP1TILUDRONATE DISODIUM
MMP8DOXYCYCLINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
MMP1214
MMP8104
SUCLG200
LGR400
MMS1900
ADAMTS1400
SERPINH100
NKAIN200
EXOSC100
KSR200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
TILUDRONATE DISODIUM4MMP1
PRAZOSIN4MMP1
SULFASALAZINE4MMP1
IRINOTECAN4MMP1
NIMESULIDE4MMP1
DOXAZOSIN4MMP1
DOXYCYCLINE4MMP8
TILUDRONIC ACID4MMP8
ZOLEDRONIC ACID4MMP8
CAFFEIC ACID3MMP1
MARIMASTAT3MMP1, MMP8
EPIGALOCATECHIN GALLATE3MMP1
QUERCETIN3MMP1
PRINOMASTAT3MMP1, MMP8
CIPEMASTAT2MMP1, MMP8
ILOMASTAT2MMP1, MMP8
APRATASTAT2MMP1
SOLIMASTAT2MMP1
TANOMASTAT2MMP1
BATIMASTAT2MMP1, MMP8
(+)-SECOISOLARICIRESINOL2MMP1
CTS-10272MMP1, MMP8
REBIMASTAT2MMP1
AMINOQUINURIDE2MMP1
AGG-5231MMP8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
MMP1588Binding:574, ADMET:10, Functional:3, Toxicity:1
MMP8238Binding:225, ADMET:9, Functional:3, Unclassified:1
KSR228Binding:28
LGR42Binding:2
SUCLG21Binding:1
MMS191Binding:1
SERPINH11Binding:1
GALNT31Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
SUCLG26.2.1.4succinate-CoA ligase (GDP-forming)
ADAMTS143.4.24.14procollagen N-endopeptidase
KSR22.7.11.25mitogen-activated protein kinase kinase kinase
ZDHHC162.3.1.225protein S-acyltransferase
GALNT32.4.1.41polypeptide N-acetylgalactosaminyltransferase
MMP13.4.24.7interstitial collagenase
MMP83.4.24.34neutrophil collagenase

Cohort genes with high screening signal

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

SymbolChEMBL assays
MMP1588
MMP8238

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

25 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.

CompoundMax phaseCohort target (bioactivity)
TILUDRONATE DISODIUM4MMP1
PRAZOSIN4MMP1
SULFASALAZINE4MMP1
IRINOTECAN4MMP1
NIMESULIDE4MMP1
DOXAZOSIN4MMP1
DOXYCYCLINE4MMP8
TILUDRONIC ACID4MMP8
ZOLEDRONIC ACID4MMP8
CAFFEIC ACID3MMP1
MARIMASTAT3MMP1, MMP8
EPIGALOCATECHIN GALLATE3MMP1
QUERCETIN3MMP1
PRINOMASTAT3MMP1, MMP8
CIPEMASTAT2MMP1, MMP8
ILOMASTAT2MMP1, MMP8
APRATASTAT2MMP1
SOLIMASTAT2MMP1
TANOMASTAT2MMP1
BATIMASTAT2MMP1, MMP8
(+)-SECOISOLARICIRESINOL2MMP1
CTS-10272MMP1, MMP8
REBIMASTAT2MMP1
AMINOQUINURIDE2MMP1
AGG-5231MMP8

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2MMP1, MMP8
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug4SUCLG2, LGR4, KSR2, FNDC3A
DDruggable family + AlphaFold only, no drug4ADAMTS14, ZDHHC16, FSTL5, GALNT3
EDifficult family or no structure, no drug12MMS19, SERPINH1, NKAIN2, EXOSC1, TMEM45B, FHOD3, LINC00466, VGLL4, SPATA31D4, LINC00645 (+2 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SUCLG21—
LGR42—
MMS191—
ADAMTS140—
SERPINH11—
NKAIN20—
EXOSC10—
KSR228—
FNDC3A0—
ZDHHC160—
FSTL50—
TMEM45B0—
FHOD30—
LINC004660—
VGLL40—
SPATA31D40—
GALNT31—
LINC006450—
MSI10—
BARX20—

Clinical trials & evidence

Clinical trials

Clinical trials: 17.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified13
PHASE41
PHASE31
PHASE2/PHASE31
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05322252PHASE4COMPLETEDSimultaneous Mifepristone and Misoprostol Versus Misoprostol Alone for Induction of Labor of Nonviable Second Trimester Pregnancy: a Pilot Randomized Controlled Trial
NCT01401179PHASE3COMPLETEDAntibiotics Study in Preterm Premature Rupture of the Membranes
NCT02939742PHASE2/PHASE3TERMINATEDDoes a Rescue Course of Betamethasone in Pregnant Women With PPROM Decrease Neonatal Morbidity?
NCT00397735PHASE1/PHASE2COMPLETEDN-acetylcysteine in Intra-amniotic Infection/Inflammation
NCT02997345Not specifiedRECRUITINGPPROM Registry (Preterm Premature Rupture of Membranes)
NCT05773014Not specifiedRECRUITINGDigital vs. Speculum Exams for PPROM
NCT06906757Not specifiedNOT_YET_RECRUITINGPreterm Rupture of Membranes Optimising Antibiotics Trial
NCT06965049Not specifiedNOT_YET_RECRUITINGVaginal Probiotics During Pregnancy After Premature (24-32 Weeks of Gestation) Preterm Rupture of Membranes
NCT07191366Not specifiedNOT_YET_RECRUITINGAntenatal Breastmilk Expression in Pregnant Women at High Risk of Preterm Birth
NCT02069587Not specifiedUNKNOWNPomegranate to Reduce Maternal and Fetal Oxidative Stress and to Improve Outcome in Pregnancies Complicated With Preterm Premature Rupture of Membranes
NCT02327637Not specifiedTERMINATEDA Comparison of Bed Rest Versus Moderate Activity in Preterm Premature Rupture of Membranes (PPROM)
NCT02386644Not specifiedCOMPLETEDTransperineal Ultrasonography and Premature Rupture of Membranes
NCT03739463Not specifiedUNKNOWNPro-omega-3, Reduction of Inflammation and Modulation of Prematurity
NCT03819192Not specifiedUNKNOWNPredicting EONS in PPROM Patients
NCT04230967Not specifiedCOMPLETEDAmbulation for Latency During Expectant Management of PPROM
NCT06443788Not specifiedCOMPLETEDTrans-perineal Ultrasound in Assessment of PPROMs
NCT06878443Not specifiedWITHDRAWNVaginal Probiotics During Pregnancy After Premature Rupture of Membranes

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CEFAZOLIN41
CLARITHROMYCIN41
ERYTHROMYCIN41
MIFEPRISTONE41
MISOPROSTOL41
OLEIC ACID21
CHEMBL406415701
MISOPROSTOL ACID-11

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot