Hydatidiform mole

Summary

Hydatidiform mole (MONDO:0006248) is a disease (an umbrella term covering 5 Mondo subtypes) with 3 cohort genes and 12 clinical trials. Top therapeutic interventions include methotrexate, dactinomycin, and vitamin b complex.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 13
• Phenotypes (HPO): 7
• Clinical trials: 12

Clinical features

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0001903	Anemia	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0005268	Spontaneous abortion	Very frequent (80-99%)
HP:0100602	Preeclampsia	Very frequent (80-99%)
HP:0100878	Enlarged uterus	Very frequent (80-99%)
HP:0400008	Menometrorrhagia	Very frequent (80-99%)
HP:0000836	Hyperthyroidism	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hydatidiform mole
Mondo ID	MONDO:0006248
EFO	EFO:1000298
MeSH	D006828
OMIM	231090
Orphanet	99927
ICD-11	946166369
NCIT	C3110
SNOMED CT	44782008
UMLS	C0020217
MedGen	9329
GARD	0010263
MedDRA	10020481
Is cancer (heuristic)	no

Also known as: hydatid mole · hydatidiform mole · HYDM · molar pregnancy

Data availability: 13 ClinVar variants · 5 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › trophoblastic neoplasm › hydatidiform mole

Related subtypes (3): testicular trophoblastic tumor, choriocarcinoma, gestational trophoblastic neoplasm

Subtypes (5): complete hydatidiform mole, partial hydatidiform mole, invasive hydatidiform mole, hydatidiform mole, recurrent, 3, hydatidiform mole, recurrent, 4

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

13 retrieved; paginated sample, class counts are floors:

5 benign, 2 likely benign, 2 benign/likely benign, 2 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
97796	NM_001127255.2(NLRP7):c.336dup (p.Glu113Glyfs)	NLRP7	Pathogenic	criteria provided, single submitter
997708	NM_001127255.2(NLRP7):c.1224_1232delGCGGGGCGCinsT (p.Arg409Alafs)	NLRP7	Pathogenic	criteria provided, single submitter
997709	NM_001127255.2(NLRP7):c.2642+17TG[6]	NCR1	Uncertain significance	criteria provided, single submitter
997710	NM_001127255.2(NLRP7):c.2695C>T (p.Leu899Phe)	NCR1	Uncertain significance	criteria provided, single submitter
997714	NM_001017361.3(KHDC3L):c.602C>G (p.Ala201Gly)	KHDC3L	Benign	criteria provided, single submitter
330158	NM_001127255.2(NLRP7):c.2682T>C (p.Tyr894=)	NCR1	Benign	criteria provided, multiple submitters, no conflicts
893861	NM_001127255.2(NLRP7):c.2706C>T (p.Ala902=)	NCR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
97770	NM_001127255.2(NLRP7):c.2811-25G>C	NCR1	Benign	criteria provided, multiple submitters, no conflicts
997711	NM_001127255.2(NLRP7):c.2811-23A>G	NCR1	Benign	criteria provided, multiple submitters, no conflicts
997712	NM_001127255.2(NLRP7):c.2982-28del	NCR1	Likely benign	criteria provided, single submitter
330164	NM_001127255.2(NLRP7):c.1725G>T (p.Leu575=)	NLRP7	Likely benign	criteria provided, multiple submitters, no conflicts
97894	NM_001127255.2(NLRP7):c.-39-16C>T	NLRP7	Benign	criteria provided, multiple submitters, no conflicts
997713	NC_000019.10:g.54947788G>A	NLRP7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NLRP7	Orphanet:254688	Complete hydatidiform mole
NLRP7	Orphanet:254693	Partial hydatidiform mole
KHDC3L	Orphanet:254688	Complete hydatidiform mole
KHDC3L	Orphanet:254693	Partial hydatidiform mole

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NLRP7	HGNC:22947	ENSG00000167634	Q8WX94	NACHT, LRR and PYD domains-containing protein 7	clinvar
KHDC3L	HGNC:33699	ENSG00000203908	Q587J8	KH domain-containing protein 3	clinvar
NCR1	HGNC:6731	ENSG00000189430	O76036	Natural cytotoxicity triggering receptor 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLRP7	NACHT, LRR and PYD domains-containing protein 7	Inhibits CASP1/caspase-1-dependent IL1B secretion.
KHDC3L	KH domain-containing protein 3	Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development.
NCR1	Natural cytotoxicity triggering receptor 1	Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · 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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLRP7	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
KHDC3L	Other/Unknown	no		MOEP19_KH-like, KH_dom_type_1_sf, KHDC1
NCR1	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_fold, Ig-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
primordial germ cell in gonad	2
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1
blood	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NLRP7	49	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, granulocyte
KHDC3L	57	tissue_specific	yes	oocyte, secondary oocyte, primordial germ cell in gonad
NCR1	100	tissue_specific	marker	granulocyte, blood, spleen

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCR1	1,569
NLRP7	1,294
KHDC3L	1,195

Intra-cohort edges

A	B	Sources
KHDC3L	NLRP7	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NCR1	O76036	4
NLRP7	Q8WX94	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KHDC3L	Q587J8	67.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.034	NCR1
Adaptive Immune System	1	29.8×	0.050	NCR1
Immune System	1	13.0×	0.077	NCR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of organelle localization	1	1872.4×	0.007	KHDC3L
regulation of natural killer cell mediated cytotoxicity	1	1404.3×	0.007	NCR1
protein storage	1	1123.5×	0.007	KHDC3L
negative regulation of protein processing	1	374.5×	0.011	NLRP7
positive regulation of embryonic development	1	374.5×	0.011	KHDC3L
positive regulation of dendrite development	1	330.4×	0.011	KHDC3L
natural killer cell activation	1	193.7×	0.013	NCR1
positive regulation of neurogenesis	1	193.7×	0.013	KHDC3L
negative regulation of interleukin-1 beta production	1	170.2×	0.013	NLRP7
immune response-regulating signaling pathway	1	151.8×	0.013	NCR1
replication fork processing	1	140.4×	0.013	KHDC3L
negative regulation of cytokine production involved in inflammatory response	1	140.4×	0.013	NLRP7
positive regulation of double-strand break repair via homologous recombination	1	127.7×	0.013	KHDC3L
positive regulation of double-strand break repair	1	114.6×	0.014	KHDC3L
cellular defense response	1	106.0×	0.014	NCR1
cellular response to interleukin-1	1	93.6×	0.015	NLRP7
regulation of protein localization	1	68.5×	0.019	KHDC3L
regulation of inflammatory response	1	56.2×	0.022	NLRP7
actin filament organization	1	39.6×	0.029	KHDC3L
cellular response to lipopolysaccharide	1	32.7×	0.033	NLRP7
negative regulation of apoptotic process	1	11.6×	0.088	KHDC3L
signal transduction	1	5.3×	0.176	NCR1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Dactinomycin	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Vitamin B Complex	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NLRP7	0	0
KHDC3L	0	0
NCR1	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
NCR1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	NCR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	NLRP7, KHDC3L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NLRP7	0	—
KHDC3L	0	—
NCR1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE3	4
PHASE4	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01630954	PHASE4	UNKNOWN	A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole
NCT00003702	PHASE3	COMPLETED	Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia
NCT01535053	PHASE3	COMPLETED	Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia
NCT01984099	PHASE3	COMPLETED	RCT on the Efficacy of Methotrexate for the Prevention of GTD
NCT04756713	PHASE3	UNKNOWN	Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia
NCT00190918	PHASE2	COMPLETED	A Trial for Patients With Gestational Trophoblastic Disease
NCT01008501	Not specified	ACTIVE_NOT_RECRUITING	Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles
NCT02892877	Not specified	RECRUITING	The French National Reference Centre of GTD
NCT03785574	Not specified	RECRUITING	Study of Different Therapeutic Strategies in Hydatidiform Mole With Lung Nodule
NCT05516810	Not specified	ACTIVE_NOT_RECRUITING	The Accuracy of Ultrasound Diagnosis of Hydatidiform Moles
NCT05637892	Not specified	NOT_YET_RECRUITING	A Cohort Study of Hydatidiform Mole
NCT07202728	Not specified	RECRUITING	A Multi-center Cohort Study of Hydatidiform Mole in China (CN-HM-01)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
METHOTREXATE	4	3
DACTINOMYCIN	4	2
VITAMIN B COMPLEX	3	1
CHEMBL4748391	0	2