Hydatidiform mole, recurrent, 2

Summary

Hydatidiform mole, recurrent, 2 (MONDO:0013671) is a disease caused by KHDC3L (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KHDC3L (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hydatidiform mole, recurrent, 2
Mondo ID	MONDO:0013671
OMIM	614293
UMLS	C3280352
MedGen	481982
GARD	0018366
Is cancer (heuristic)	no

Also known as: complete hydatidiform mole caused by mutation in KHDC3L · hydatidiform mole, recurrent, 2 · hydatidiform Mole, recurrent, type 2 · HYDM2 · KHDC3L complete hydatidiform mole

Data availability: 5 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, 2

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

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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
157611	NM_001017361.3(KHDC3L):c.299_302del (p.Ile100fs)	KHDC3L	Pathogenic	no assertion criteria provided
30926	NM_001017361.3(KHDC3L):c.3G>T (p.Met1Ile)	KHDC3L	Pathogenic	no assertion criteria provided
30927	NM_001017361.3(KHDC3L):c.322_325del (p.Asp108fs)	KHDC3L	Pathogenic	no assertion criteria provided
208592	NM_001017361.3(KHDC3L):c.334C>T (p.Gln112Ter)	KHDC3L	Likely pathogenic	criteria provided, single submitter
30928	NM_001017361.3(KHDC3L):c.1A>G (p.Met1Val)	KHDC3L	Uncertain significance	criteria provided, single submitter

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
KHDC3L	Strong	Autosomal recessive	hydatidiform mole, recurrent, 2	3

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KHDC3L	HGNC:33699	ENSG00000203908	Q587J8	KH domain-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KHDC3L	Other/Unknown	no		MOEP19_KH-like, KH_dom_type_1_sf, KHDC1

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KHDC3L	57	tissue_specific	yes	oocyte, secondary oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KHDC3L	1,195

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KHDC3L	Q587J8	67.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of organelle localization	1	5617.3×	0.002	KHDC3L
protein storage	1	3370.4×	0.002	KHDC3L
positive regulation of embryonic development	1	1123.5×	0.003	KHDC3L
positive regulation of dendrite development	1	991.3×	0.003	KHDC3L
positive regulation of neurogenesis	1	581.1×	0.004	KHDC3L
replication fork processing	1	421.3×	0.004	KHDC3L
positive regulation of double-strand break repair via homologous recombination	1	383.0×	0.004	KHDC3L
positive regulation of double-strand break repair	1	343.9×	0.004	KHDC3L
regulation of protein localization	1	205.5×	0.006	KHDC3L
actin filament organization	1	118.7×	0.009	KHDC3L
negative regulation of apoptotic process	1	34.8×	0.029	KHDC3L

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KHDC3L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
E	Difficult family or no structure, no drug	1	KHDC3L

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.