Microcephaly with lissencephaly and/or hydranencephaly

Summary

Microcephaly with lissencephaly and/or hydranencephaly (MONDO:0700116) is a disease caused by NDE1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NDE1 (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly with lissencephaly and/or hydranencephaly
Mondo ID	MONDO:0700116
GARD	0026362
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › microcephaly › microcephaly with lissencephaly and/or hydranencephaly

Related subtypes (9): microcephalic osteodysplastic primordial dwarfism, microcephaly and chorioretinopathy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Amish lethal microcephaly, microcephaly, seizures, and developmental delay, isolated congenital microcephaly, isolated microcephaly, microcephaly with intellectual disability, microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia

Subtypes (2): NDE1-related microhydranencephaly, lissencephaly 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
NDE1	Definitive	Autosomal recessive	lissencephaly 4	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDE1	Orphanet:2177	Hydranencephaly
NDE1	Orphanet:443162	NDE1-related microhydranencephaly
NDE1	Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type

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
NDE1	HGNC:17619	ENSG00000072864	Q9NXR1	Nuclear distribution protein nudE homolog 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDE1	Nuclear distribution protein nudE homolog 1	Required for centrosome duplication and formation and function of the mitotic spindle.

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)
NDE1	Other/Unknown	no		NUDE_dom, NUDE

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
corpus callosum	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDE1	134	ubiquitous	marker	colonic epithelium, ventricular zone, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDE1	1,761

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDE1	Q9NXR1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 1 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
Centrosome maturation	1	253.8×	0.018	NDE1
Amplification of signal from the kinetochores	1	196.9×	0.018	NDE1
Loss of Nlp from mitotic centrosomes	1	158.6×	0.018	NDE1
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.018	NDE1
Mitotic Spindle Checkpoint	1	158.6×	0.018	NDE1
AURKA Activation by TPX2	1	152.3×	0.018	NDE1
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.018	NDE1
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.018	NDE1
Mitotic G2-G2/M phases	1	126.9×	0.018	NDE1
G2/M Transition	1	126.9×	0.018	NDE1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.018	NDE1
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.018	NDE1
Anchoring of the basal body to the plasma membrane	1	113.1×	0.018	NDE1
Cilium Assembly	1	108.8×	0.018	NDE1
Mitotic Metaphase and Anaphase	1	96.8×	0.018	NDE1
Mitotic Anaphase	1	96.8×	0.018	NDE1
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.018	NDE1
Cell Cycle Checkpoints	1	88.5×	0.018	NDE1
Resolution of Sister Chromatid Cohesion	1	86.5×	0.018	NDE1
RHO GTPases Activate Formins	1	77.7×	0.019	NDE1
Mitotic Prometaphase	1	69.2×	0.019	NDE1
RHO GTPase Effectors	1	68.0×	0.019	NDE1
Organelle biogenesis and maintenance	1	66.0×	0.019	NDE1
M Phase	1	66.0×	0.019	NDE1
Separation of Sister Chromatids	1	60.7×	0.020	NDE1
Cell Cycle, Mitotic	1	48.2×	0.024	NDE1
Cell Cycle	1	36.0×	0.031	NDE1
Signaling by Rho GTPases	1	34.2×	0.031	NDE1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.031	NDE1
Signal Transduction	1	10.2×	0.098	NDE1

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
chromosome localization	1	8426.0×	0.002	NDE1
mitotic centrosome separation	1	2808.7×	0.002	NDE1
centrosome duplication	1	936.2×	0.003	NDE1
vesicle transport along microtubule	1	887.0×	0.003	NDE1
centrosome localization	1	887.0×	0.003	NDE1
microtubule nucleation	1	624.1×	0.003	NDE1
establishment of mitotic spindle orientation	1	481.5×	0.004	NDE1
neuroblast proliferation	1	366.4×	0.004	NDE1
cerebral cortex development	1	205.5×	0.007	NDE1
chromosome segregation	1	173.7×	0.007	NDE1
neuron migration	1	133.8×	0.009	NDE1
cell migration	1	61.5×	0.018	NDE1
cell division	1	46.2×	0.022	NDE1

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
NDE1	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	NDE1

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)
NDE1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.