Hydatidiform mole, recurrent, 1

Summary

Hydatidiform mole, recurrent, 1 (MONDO:0009273) is a disease caused by NLRP7 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: NLRP7 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 217

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hydatidiform mole, recurrent, 1
Mondo ID	MONDO:0009273
OMIM	231090
UMLS	C3463897
MedGen	483038
GARD	0018365
Is cancer (heuristic)	no

Also known as: complete hydatidiform mole caused by mutation in NLRP7 · hydatidiform mole, recurrent, 1 · hydatidiform Mole, recurrent, type 1 · HYDM1 · NLRP7 complete hydatidiform mole

Data availability: 217 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › trophoblastic neoplasm › hydatidiform mole › complete hydatidiform mole › hydatidiform mole, recurrent, 1

Related subtypes (1): hydatidiform mole, recurrent, 2

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

217 retrieved; paginated sample, class counts are floors:

85 not provided, 72 uncertain significance, 16 pathogenic, 15 conflicting classifications of pathogenicity, 13 benign, 9 likely benign, 5 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1585	NM_001127255.2(NLRP7):c.2471+1G>A	NCR1	Pathogenic	criteria provided, single submitter
1591	NM_001127255.2(NLRP7):c.2078G>A (p.Arg693Gln)	NCR1	Pathogenic	criteria provided, single submitter
3235890	NM_001127255.2(NLRP7):c.2585G>A (p.Gly862Glu)	NCR1	Pathogenic	no assertion criteria provided
41407	NM_001127255.2(NLRP7):c.2030delT (p.Leu677Profs)	NCR1	Pathogenic	no assertion criteria provided
97748	NM_001127255.2(NLRP7):c.2161C>T (p.Arg721Trp)	NCR1	Pathogenic	criteria provided, single submitter
97750	NM_001127255.2(NLRP7):c.2248C>G (p.Leu750Val)	NCR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1584	NM_001127255.2(NLRP7):c.352+1G>A	NLRP7	Pathogenic	no assertion criteria provided
1586	NM_001127255.2(NLRP7):c.2077C>T (p.Arg693Trp)	NLRP7	Pathogenic	criteria provided, single submitter
1587	NM_001127255.2(NLRP7):c.2078G>C (p.Arg693Pro)	NLRP7	Pathogenic	criteria provided, single submitter
1589	NM_001127255.2(NLRP7):c.1294C>T (p.Arg432Ter)	NLRP7	Pathogenic	no assertion criteria provided
1592	NM_001127255.2(NLRP7):c.1193T>G (p.Leu398Arg)	NLRP7	Pathogenic	no assertion criteria provided
1593	NM_001127255.2(NLRP7):c.1951C>T (p.Pro651Ser)	NLRP7	Pathogenic	no assertion criteria provided
4293511	NM_001127255.2(NLRP7):c.818G>A (p.Trp273Ter)	NLRP7	Pathogenic	criteria provided, single submitter
812700	NM_001127255.2(NLRP7):c.1857_1858delAC (p.Lys619Asnfs)	NLRP7	Pathogenic	no assertion criteria provided
97796	NM_001127255.2(NLRP7):c.336dup (p.Glu113Glyfs)	NLRP7	Pathogenic	criteria provided, single submitter
97807	NM_001127255.2(NLRP7):c.939_952dup (p.Tyr318Cysfs)	NLRP7	Pathogenic	no assertion criteria provided
1588	NM_001127255.2(NLRP7):c.2738A>G (p.Asn913Ser)	NCR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376766	NM_001127255.2(NLRP7):c.2177C>T (p.Ala726Val)	NCR1	Likely pathogenic	criteria provided, single submitter
3382290	NM_001127255.2(NLRP7):c.2218_2224del (p.Gly740fs)	NCR1	Likely pathogenic	criteria provided, single submitter
830330	NM_001127255.2(NLRP7):c.2320_2321insT (p.Thr774Ilefs)	NCR1	Likely pathogenic	criteria provided, single submitter
2571601	NM_001127255.2(NLRP7):c.277+1G>A	NLRP7	Likely pathogenic	criteria provided, single submitter
97715	NM_001127255.2(NLRP7):c.1137G>C (p.Lys379Asn)	KIR3DL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330160	NM_001127255.2(NLRP7):c.2384G>A (p.Arg795His)	NCR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
97734	NM_001127255.2(NLRP7):c.2094C>T (p.His698=)	NCR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
97735	NM_001127255.2(NLRP7):c.2095G>A (p.Val699Ile)	NCR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
97747	NM_001127255.2(NLRP7):c.2156C>T (p.Ala719Val)	NCR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031155	NM_001127255.2(NLRP7):c.298A>G (p.Ile100Val)	NLRP7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288252	NM_001127255.2(NLRP7):c.1082C>T (p.Ser361Leu)	NLRP7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330181	NM_001127255.2(NLRP7):c.531C>T (p.His177=)	NLRP7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892830	NM_001127255.2(NLRP7):c.1149G>A (p.Pro383=)	NLRP7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NLRP7	Strong	Autosomal recessive	hydatidiform mole, recurrent, 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NLRP7	Orphanet:254688	Complete hydatidiform mole
NLRP7	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	gencc,clinvar
KIR3DL1	HGNC:6338	ENSG00000167633	P43629	Killer cell immunoglobulin-like receptor 3DL1	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.
KIR3DL1	Killer cell immunoglobulin-like receptor 3DL1	Receptor on natural killer (NK) cells for HLA Bw4 allele.
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: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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	2	19.5×	0.007
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLRP7	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
KIR3DL1	Antibody/Immunoglobulin	yes		Ig_sub, Immunoglobulin_dom, Ig-like_fold
NCR1	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_fold, Ig-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
blood	2
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
buccal mucosa cell	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
KIR3DL1	44		marker	granulocyte, buccal mucosa cell, blood
NCR1	100	tissue_specific	marker	granulocyte, blood, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCR1	1,569
NLRP7	1,294
KIR3DL1	877

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIR3DL1	P43629	18
NCR1	O76036	4
NLRP7	Q8WX94	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 evidence-associated genes (2 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 2 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	2	87.2×	4e-04	KIR3DL1, NCR1
Adaptive Immune System	2	29.8×	0.002	KIR3DL1, NCR1
Immune System	2	13.0×	0.006	KIR3DL1, 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
immune response-regulating signaling pathway	2	303.6×	2e-04	KIR3DL1, NCR1
regulation of natural killer cell mediated cytotoxicity	1	1404.3×	0.005	NCR1
negative regulation of protein processing	1	374.5×	0.012	NLRP7
natural killer cell activation	1	193.7×	0.013	NCR1
negative regulation of interleukin-1 beta production	1	170.2×	0.013	NLRP7
natural killer cell mediated cytotoxicity	1	144.0×	0.013	KIR3DL1
negative regulation of cytokine production involved in inflammatory response	1	140.4×	0.013	NLRP7
cellular defense response	1	106.0×	0.015	NCR1
cellular response to interleukin-1	1	93.6×	0.015	NLRP7
regulation of inflammatory response	1	56.2×	0.023	NLRP7
cellular response to lipopolysaccharide	1	32.7×	0.036	NLRP7
immune response	1	15.7×	0.068	KIR3DL1
signal transduction	1	5.3×	0.176	NCR1

Therapeutics

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
KIR3DL1	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	2	KIR3DL1, NCR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NLRP7

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	—
KIR3DL1	0	—
NCR1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.