Oligohydramnios

Summary

Oligohydramnios (MONDO:0005881) is a disease with 6 cohort genes and 18 clinical trials. Top therapeutic interventions include warfarin.

At a glance

• Cohort genes: 6
• ClinVar variants: 10
• Clinical trials: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oligohydramnios
Mondo ID	MONDO:0005881
EFO	EFO:0007401
MeSH	D016104
DOID	DOID:12215
ICD-10-CM	O41.0
ICD-11	262953341
SNOMED CT	59566000
UMLS	C0079924
MedGen	86974
Is cancer (heuristic)	no

Also known as: oligohydramnios · oligohydramnios (disease)

Data availability: 10 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

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

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

Subtypes (1): Potter sequence

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

10 retrieved; paginated sample, class counts are floors:

3 pathogenic/likely pathogenic, 3 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
268039	46;XY;t(3;18)(q13.31;q22.1)dn		Pathogenic	criteria provided, single submitter
523401	NM_001378615.1(CC2D2A):c.1149+1G>A	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56312	NM_001378615.1(CC2D2A):c.4179+1del	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
4108	NM_138694.4(PKHD1):c.107C>T (p.Thr36Met)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1383	NM_153704.6(TMEM67):c.1843T>C (p.Cys615Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374192	NM_002547.3(OPHN1):c.746T>C (p.Leu249Pro)	OPHN1	Likely pathogenic	criteria provided, single submitter
217725	NM_153704.6(TMEM67):c.1321C>T (p.Arg441Cys)	TMEM67	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523532	NM_022489.4(INF2):c.3247A>G (p.Ser1083Gly)	INF2	Uncertain significance	criteria provided, single submitter
623485	NM_014462.3(LSM1):c.231+4A>C	LSM1	Uncertain significance	criteria provided, multiple submitters, no conflicts
374193	NM_138694.4(PKHD1):c.2716-3C>G	PKHD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
INF2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
INF2	Orphanet:93114	Autosomal dominant intermediate Charcot-Marie-Tooth disease type E
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
CC2D2A	Orphanet:1454	Joubert syndrome with hepatic defect
CC2D2A	Orphanet:2318	Joubert syndrome with oculorenal defect
CC2D2A	Orphanet:564	Meckel syndrome
CC2D2A	Orphanet:791	Retinitis pigmentosa
OPHN1	Orphanet:137831	X-linked intellectual disability-cerebellar hypoplasia syndrome
PKHD1	Orphanet:53035	Caroli disease
PKHD1	Orphanet:731	Autosomal recessive polycystic kidney disease

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LSM1	HGNC:20472	ENSG00000175324	O15116	U6 snRNA-associated Sm-like protein LSm1	clinvar
INF2	HGNC:23791	ENSG00000203485	Q27J81	Inverted formin-2	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar
OPHN1	HGNC:8148	ENSG00000079482	O60890	Oligophrenin-1	clinvar
PKHD1	HGNC:9016	ENSG00000170927	P08F94	Fibrocystin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LSM1	U6 snRNA-associated Sm-like protein LSm1	Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated.
INF2	Inverted formin-2	Severs actin filaments and accelerates their polymerization and depolymerization.
TMEM67	Meckelin	Required for ciliary structure and function.
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
OPHN1	Oligophrenin-1	Stimulates GTP hydrolysis of members of the Rho family.
PKHD1	Fibrocystin	Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/ or ensures the maintenance of the architecture of the lumen of the kidney.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · 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
Protease	1	6.1×	0.377
Antibody/Immunoglobulin	1	4.9×	0.377
Scaffold/PPI	1	2.9×	0.401
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LSM1	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm1
INF2	Other/Unknown	no		WH2_dom, FH3_dom, GTPase-bd
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
OPHN1	Scaffold/PPI	no		RhoGAP_dom, PH_domain, BAR_dom
PKHD1	Antibody/Immunoglobulin	yes		IPT_dom, PbH1, Pectin_lyase_fold/virulence

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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
calcaneal tendon	2
right uterine tube	2
gingival epithelium	1
hair follicle	1
parotid gland	1
nerve	1
tibial nerve	1
buccal mucosa cell	1
bronchial epithelial cell	1
bronchus	1
corpus callosum	1
kidney epithelium	1
metanephros cortex	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LSM1	296	ubiquitous	marker	parotid gland, gingival epithelium, hair follicle
INF2	260	ubiquitous	marker	sural nerve, nerve, tibial nerve
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
OPHN1	138	ubiquitous	marker	corpus callosum, calcaneal tendon, sural nerve
PKHD1	51	tissue_specific	marker	kidney epithelium, renal medulla, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INF2	2,070
LSM1	2,060
OPHN1	1,229
PKHD1	1,211
TMEM67	1,194
CC2D2A	899

Intra-cohort edges

A	B	Sources
CC2D2A	TMEM67	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INF2	Q27J81	10
TMEM67	Q5HYA8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LSM1	O15116	89.59
OPHN1	O60890	74.86
CC2D2A	Q9P2K1	69.46
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 6 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
Anchoring of the basal body to the plasma membrane	2	56.5×	0.004	TMEM67, CC2D2A
Cilium Assembly	2	54.4×	0.004	TMEM67, CC2D2A
Organelle biogenesis and maintenance	2	33.0×	0.007	TMEM67, CC2D2A
Deadenylation-dependent mRNA decay	1	219.6×	0.017	LSM1
mRNA decay by 5’ to 3’ exoribonuclease	1	190.3×	0.017	LSM1
RHOJ GTPase cycle	1	50.1×	0.043	OPHN1
RHOQ GTPase cycle	1	45.3×	0.043	OPHN1
RHOB GTPase cycle	1	38.6×	0.043	OPHN1
RHOG GTPase cycle	1	37.1×	0.043	OPHN1
RHOC GTPase cycle	1	36.6×	0.043	OPHN1
RAC2 GTPase cycle	1	31.7×	0.044	OPHN1
RAC3 GTPase cycle	1	29.7×	0.044	OPHN1
RHOA GTPase cycle	1	18.7×	0.062	OPHN1
CDC42 GTPase cycle	1	18.1×	0.062	OPHN1
RAC1 GTPase cycle	1	15.3×	0.068	OPHN1
Metabolism of RNA	1	10.4×	0.093	LSM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	3	36.8×	0.003	TMEM67, CC2D2A, PKHD1
regulation of cholangiocyte proliferation	1	2808.7×	0.012	PKHD1
maintenance of postsynaptic specialization structure	1	936.2×	0.015	OPHN1
negative regulation of centrosome duplication	1	561.7×	0.015	TMEM67
regulation of establishment of planar polarity	1	468.1×	0.015	PKHD1
protein localization to ciliary transition zone	1	401.2×	0.015	CC2D2A
cerebellar granule cell differentiation	1	351.1×	0.015	OPHN1
regulation of mitochondrial fission	1	351.1×	0.015	INF2
deadenylation-dependent decapping of nuclear-transcribed mRNA	1	280.9×	0.015	LSM1
cell junction assembly	1	280.9×	0.015	OPHN1
homeostatic process	1	280.9×	0.015	PKHD1
establishment of centrosome localization	1	280.9×	0.015	PKHD1
histone mRNA catabolic process	1	280.9×	0.015	LSM1
substrate-dependent cell migration, cell extension	1	255.3×	0.015	OPHN1
cell morphogenesis involved in neuron differentiation	1	255.3×	0.015	OPHN1
negative regulation of proteasomal protein catabolic process	1	234.1×	0.015	OPHN1
regulation of cell-matrix adhesion	1	216.1×	0.015	PKHD1
cerebral cortex neuron differentiation	1	200.6×	0.015	OPHN1
regulation of cell-cell adhesion	1	200.6×	0.015	PKHD1
negative regulation of epithelial cell apoptotic process	1	200.6×	0.015	PKHD1
kidney development	2	46.8×	0.015	CC2D2A, PKHD1
neuron differentiation	2	33.4×	0.015	LSM1, OPHN1
establishment of epithelial cell apical/basal polarity	1	175.5×	0.016	OPHN1
epithelial cell morphogenesis	1	156.0×	0.017	PKHD1
regulation of TOR signaling	1	156.0×	0.017	PKHD1
regulation of synaptic vesicle endocytosis	1	147.8×	0.017	OPHN1
embryonic brain development	1	133.8×	0.018	CC2D2A
regulation of centrosome duplication	1	122.1×	0.019	PKHD1
branching morphogenesis of an epithelial tube	1	122.1×	0.019	PKHD1
RNA splicing, via transesterification reactions	1	104.0×	0.019	LSM1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

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

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 1 of 6 evidence-associated genes (17%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LSM1	0	0
INF2	0	0
TMEM67	0	0
CC2D2A	0	0
OPHN1	0	0
PKHD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
INF2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	CC2D2A, PKHD1
E	Difficult family or no structure, no drug	4	LSM1, INF2, TMEM67, OPHN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LSM1	0	—
INF2	1	—
TMEM67	0	—
CC2D2A	0	—
OPHN1	0	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 18.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE4	1
PHASE3	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01569035	PHASE4	TERMINATED	Warfarine in Unexplained Oligohydramnios
NCT00787163	PHASE3	UNKNOWN	Amnioinfusion Initiative
NCT07135037	PHASE2	RECRUITING	Comparison Between Treatments of Oligohydramnios
NCT01258725	PHASE1	UNKNOWN	Alterations of the Uteroplacental and Fetal Pulmonary Circulation Following Amnioinfusion
NCT02997345	Not specified	RECRUITING	PPROM Registry (Preterm Premature Rupture of Membranes)
NCT04451109	Not specified	ACTIVE_NOT_RECRUITING	Dilapan-S®: A Multicenter US E-registry
NCT05043753	Not specified	RECRUITING	Fetal gRowth AbnorMality dEtection Trial
NCT01140971	Not specified	COMPLETED	Foley Catheter Versus Vaginal Misoprostol for Cervical Ripening and Induction of Labor
NCT01682928	Not specified	TERMINATED	Hydrotherapy for the Reversal of Oligohydramnios
NCT02581774	Not specified	COMPLETED	Active Induction of Labor in Pregnancies Complicated With Oligohydramnios at Term
NCT02901340	Not specified	UNKNOWN	Fetal Renal Artery Doppler Indices in Borderline Isolated Oligohydramnios
NCT03277417	Not specified	UNKNOWN	Does Amniotic Fluid Index Affect the Fetal Cardiac Performance?
NCT03815968	Not specified	UNKNOWN	Low Sodium Diet in Oligohydramnios Assigned for Conservative Management
NCT03935607	Not specified	COMPLETED	The Added Contribution of Transvaginal Sonographic Evaluation of Amniotic Fluid Index
NCT04684680	Not specified	UNKNOWN	The Role of Zamzam Water in Idiopathic Oligohydramnios
NCT05059093	Not specified	COMPLETED	Developing and Testing AI Models for Fetal Biometry and Amniotic Volume Assessment in Fetal Ultrasound Scans.
NCT05332015	Not specified	COMPLETED	The Effect of Oral Hypotonic Hydration in Isolated Oligohydramnios
NCT05474326	Not specified	UNKNOWN	Effect of Intermittent Pneumatic Compression Device of Lower Limbs in Oligohydramnios

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
WARFARIN	4	1