Placental abruption

Summary

Placental abruption (MONDO:0004846) is a disease with 7 cohort genes (10 GWAS associations across 3 studies) and 13 clinical trials. Top therapeutic interventions include magnesium sulfate.

At a glance

• Cohort genes: 7
• GWAS associations: 10
• Clinical trials: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	placental abruption
Mondo ID	MONDO:0004846
EFO	EFO:1001754
MeSH	D000037
DOID	DOID:9667
ICD-10-CM	O45
NCIT	C26685
SNOMED CT	415105001
UMLS	C0000832
MedGen	49
Is cancer (heuristic)	no

Also known as: abruptio placentae · Abruptio placentae, premature separation of placenta · placental abruption · placental abruption (disease) · premature separation of placenta

Data availability: 10 GWAS associations (3 studies) · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › female reproductive system disorder › uterine disorder › placenta disorder › placental abruption

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

Genetics & variants

GWAS landscape

10 GWAS associations across 3 studies. Top hits map to 8 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs145505746	9e-09	PATJ	?
rs76258369	3e-06	LINC01019 - IRX1	T	1.56
rs7094759	4e-06	ADAM12	?	1.35
rs30080	5e-06	DOCK2	?	1.37
rs4867606	5e-06	KCNIP1	A	1.82
rs11995662	5e-06	PDGFRL	?	1.64
rs219551	6e-06	TDRD15 - NUTF2P8	T	1.64
rs799758	8e-06	GALNT13	T	1.47
rs2291228	8e-06	DOCK2, INSYN2B	A	1.37
rs17837210	9e-06	FAM124A	A	1.8

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90454240	Pujol Gualdo N	2025	1,065	268,941	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST005844	Workalemahu T	2018	959	0	Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies.
GCST90651453	Liu TY	2025	367	123,916	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	8

MAF distribution

Bucket	Variants
common (>=0.05)	9
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	7
3_prime_UTR_variant	2
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs145505746	1	61911307	G>A		intron_variant	PATJ	9e-09	Tier 4: intronic/intergenic
rs76258369	5	3545433	T>C	0.05	intergenic_variant	LINC01019 - IRX1	3e-06	Tier 4: intronic/intergenic
rs7094759	10	126163537	A>T	0.05	intron_variant	ADAM12	4e-06	Tier 4: intronic/intergenic
rs30080	5	169846553	G>A,C,T	0.05	intron_variant	DOCK2	5e-06	Tier 4: intronic/intergenic
rs4867606	5	170497691	G>A	0.05	intron_variant	KCNIP1	5e-06	Tier 4: intronic/intergenic
rs11995662	8	17641221	T>C,G	0.05	intron_variant	PDGFRL	5e-06	Tier 4: intronic/intergenic
rs219551	2	21317839	C>A,T	0.05	intron_variant	TDRD15 - NUTF2P8	6e-06	Tier 4: intronic/intergenic
rs799758	2	154405632	T>C	0.05	intron_variant	GALNT13	8e-06	Tier 4: intronic/intergenic
rs2291228	5	169861728	A>G	0.05	3_prime_UTR_variant	DOCK2, INSYN2B	8e-06	Tier 2: splice/UTR
rs17837210	13	51281874	A>C	0.05	3_prime_UTR_variant	FAM124A	9e-06	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DOCK2	Orphanet:447737	Combined immunodeficiency due to DOCK2 deficiency
PDGFRL	Orphanet:210159	Adult hepatocellular carcinoma

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNIP1	HGNC:15521	ENSG00000182132	Q9NZI2	A-type potassium channel modulatory protein KCNIP1	gwas
ADAM12	HGNC:190	ENSG00000148848	O43184	Disintegrin and metalloproteinase domain-containing protein 12	gwas
GALNT13	HGNC:23242	ENSG00000144278	Q8IUC8	Polypeptide N-acetylgalactosaminyltransferase 13	gwas
FAM124A	HGNC:26413	ENSG00000150510	Q86V42	Protein FAM124A	gwas
DOCK2	HGNC:2988	ENSG00000134516	Q92608	Dedicator of cytokinesis protein 2	gwas
INSYN2B	HGNC:37271	ENSG00000204767	A6NMK8	Protein INSYN2B	gwas
PDGFRL	HGNC:8805	ENSG00000104213	Q15198	Platelet-derived growth factor receptor-like protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNIP1	A-type potassium channel modulatory protein KCNIP1	Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels.
ADAM12	Disintegrin and metalloproteinase domain-containing protein 12	Involved in skeletal muscle regeneration, specifically at the onset of cell fusion.
GALNT13	Polypeptide N-acetylgalactosaminyltransferase 13	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.
DOCK2	Dedicator of cytokinesis protein 2	Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.43

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
Protease	1	5.2×	0.541
Antibody/Immunoglobulin	1	4.2×	0.541
Scaffold/PPI	1	2.5×	0.568
Enzyme (other)	1	1.7×	0.571
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNIP1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
ADAM12	Protease	yes	3.4.24.B10	EGF, Peptidase_M12B, Disintegrin_dom
GALNT13	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
FAM124A	Other/Unknown	no		FAM124, FAM124_dom
DOCK2	Scaffold/PPI	no		SH3_domain, ARM-type_fold, DOCK
INSYN2B	Other/Unknown	no		INSYN2
PDGFRL	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
bone marrow cell	2
anterior cingulate cortex	1
cingulate cortex	1
nucleus accumbens	1
buccal mucosa cell	1
placenta	1
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1
C1 segment of cervical spinal cord	1
corpus callosum	1
inferior vagus X ganglion	1
monocyte	1
mononuclear cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
pericardium	1
synovial joint	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNIP1	162	broad	marker	nucleus accumbens, anterior cingulate cortex, cingulate cortex
ADAM12	187	ubiquitous	marker	placenta, stromal cell of endometrium, buccal mucosa cell
GALNT13	184	broad	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
FAM124A	205	broad	marker	inferior vagus X ganglion, corpus callosum, C1 segment of cervical spinal cord
DOCK2	216	broad	marker	bone marrow cell, monocyte, mononuclear cell
INSYN2B	149	broad	yes	stromal cell of endometrium, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis
PDGFRL	236	ubiquitous	marker	pericardium, tendon of biceps brachii, synovial joint

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNIP1	2,676
DOCK2	2,278
ADAM12	1,420
PDGFRL	1,129
GALNT13	977
FAM124A	596
INSYN2B	521

Intra-cohort edges

A	B	Sources
FAM124A	INSYN2B	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNIP1	Q9NZI2	10
DOCK2	Q92608	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GALNT13	Q8IUC8	93.06
PDGFRL	Q15198	83.54
ADAM12	O43184	72.11
FAM124A	Q86V42	63.48
INSYN2B	A6NMK8	53.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 7 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Invadopodia formation	1	713.8×	0.017	ADAM12
Phase 1 - inactivation of fast Na+ channels	1	407.9×	0.017	KCNIP1
Nef and signal transduction	1	317.2×	0.017	DOCK2
Signaling by EGFR	1	81.6×	0.049	ADAM12
O-linked glycosylation of mucins	1	46.0×	0.069	GALNT13
RHOG GTPase cycle	1	37.1×	0.071	DOCK2
RAC2 GTPase cycle	1	31.7×	0.071	DOCK2
Cardiac conduction	1	27.2×	0.073	KCNIP1
Muscle contraction	1	19.3×	0.079	KCNIP1
RHOA GTPase cycle	1	18.7×	0.079	DOCK2
Factors involved in megakaryocyte development and platelet production	1	16.6×	0.079	DOCK2
Extracellular matrix organization	1	15.8×	0.079	ADAM12
RAC1 GTPase cycle	1	15.3×	0.079	DOCK2
Signaling by Receptor Tyrosine Kinases	1	12.9×	0.086	ADAM12
Neutrophil degranulation	1	5.8×	0.173	DOCK2
Signal Transduction	1	2.5×	0.339	ADAM12

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
myoblast fusion	2	300.9×	4e-04	ADAM12, DOCK2
membrane raft polarization	1	1404.3×	0.005	DOCK2
myeloid dendritic cell activation involved in immune response	1	1404.3×	0.005	DOCK2
alpha-beta T cell proliferation	1	1404.3×	0.005	DOCK2
establishment of T cell polarity	1	468.1×	0.008	DOCK2
macropinocytosis	1	468.1×	0.008	DOCK2
positive thymic T cell selection	1	351.1×	0.008	DOCK2
negative thymic T cell selection	1	351.1×	0.008	DOCK2
immunological synapse formation	1	324.1×	0.008	DOCK2
membrane repolarization	1	324.1×	0.008	KCNIP1
potassium ion export across plasma membrane	1	263.3×	0.009	KCNIP1
regulation of potassium ion transmembrane transport	1	156.0×	0.014	KCNIP1
regulation of heart contraction	1	123.9×	0.017	KCNIP1
protein O-linked glycosylation via N-acetylgalactosamine	1	108.0×	0.018	GALNT13
positive regulation of phagocytosis	1	79.5×	0.023	DOCK2
regulation of signal transduction	1	66.9×	0.025	KCNIP1
protein O-linked glycosylation	1	56.2×	0.028	GALNT13
muscle contraction	1	52.0×	0.029	KCNIP1
small GTPase-mediated signal transduction	1	45.8×	0.031	DOCK2
regulation of small GTPase mediated signal transduction	1	36.0×	0.037	DOCK2
chemotaxis	1	34.0×	0.037	DOCK2
positive regulation of angiogenesis	1	28.9×	0.042	ADAM12
actin cytoskeleton organization	1	19.8×	0.057	DOCK2
chemical synaptic transmission	1	19.3×	0.057	KCNIP1
cell migration	1	15.4×	0.069	DOCK2
cell adhesion	1	9.4×	0.107	ADAM12
proteolysis	1	8.6×	0.112	ADAM12

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Magnesium Sulfate Anhydrous	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAM12	1	2
DOCK2	1	2
KCNIP1	0	0
GALNT13	0	0
FAM124A	0	0
INSYN2B	0	0
PDGFRL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ILOMASTAT	2	ADAM12
MOLIBRESIB	2	DOCK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
DOCK2	11	Binding:11
ADAM12	2	Binding:2
GALNT13	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAM12	3.4.24.B10
GALNT13	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
ILOMASTAT	2	ADAM12
MOLIBRESIB	2	DOCK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	2	ADAM12, DOCK2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	GALNT13, PDGFRL
E	Difficult family or no structure, no drug	3	KCNIP1, FAM124A, INSYN2B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KCNIP1	0	—
GALNT13	1	—
FAM124A	0	—
INSYN2B	0	—
PDGFRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT07263490	Not specified	RECRUITING	PRIOR Study (Pre-eclampsia Risk In Oocyte Recipients)
NCT00186069	Not specified	COMPLETED	Magnesium Sulfate vs Placebo for Placental Abruption
NCT00573118	Not specified	UNKNOWN	Severe Pregnancy Complications Are Associated With Elevated Factor VIII Plasma Activity
NCT01068795	Not specified	COMPLETED	Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome
NCT01279369	Not specified	TERMINATED	The Use of Fetal Fibronectin to Predict Delivery Due to Abruptio Placenta
NCT01501890	Not specified	WITHDRAWN	Progesterone for First Trimester Vaginal Bleeding
NCT03455387	Not specified	COMPLETED	Evaluation of the Serum Markers sFLt1 and PlGF for the Prediction of the Complications of the Placental Vascular Pathologies in the 3rd Quarter of the Pregnancy.
NCT03782168	Not specified	TERMINATED	Plasma Concentration of Biological Markers in Placental Abruption
NCT04168606	Not specified	COMPLETED	Study on Retroplacental Hematomas in Finistère
NCT04558996	Not specified	UNKNOWN	Spanish Registry of Pregnant Women With COVID-19
NCT06653374	Not specified	COMPLETED	Perinatal Conditions Influencing Morbidity, Mortality, and Medical Care in Newborns

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MAGNESIUM SULFATE	4	2