NDE1-related microhydranencephaly

Summary

NDE1-related microhydranencephaly (MONDO:0011504) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	NDE1-related microhydranencephaly
Mondo ID	MONDO:0011504
MeSH	C537555
OMIM	605013
Orphanet	443162
UMLS	C1857977
MedGen	341899
GARD	0010216
Is cancer (heuristic)	no

Also known as: MHAC · microhydranencephaly

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › sporadic fetal brain disruption sequence › NDE1-related microhydranencephaly

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

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1696425	NM_017668.3(NDE1):c.54G>A (p.Trp18Ter)	NDE1	Pathogenic	no assertion criteria provided
224608	NM_017668.3(NDE1):c.-43-3548_83+622del	NDE1	Pathogenic	no assertion criteria provided
30787	NM_017668.3(NDE1):c.684_685del (p.Pro229fs)	NDE1	Pathogenic	criteria provided, multiple submitters, no conflicts
3764542	NM_017668.3(NDE1):c.734del (p.Leu245fs)	NDE1	Likely pathogenic	criteria provided, single submitter
159020	NM_017668.3(NDE1):c.872C>T (p.Ser291Phe)	NDE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030209	NM_017668.3(NDE1):c.568A>G (p.Arg190Gly)	NDE1	Uncertain significance	criteria provided, single submitter
211577	NM_017668.3(NDE1):c.155C>T (p.Thr52Met)	NDE1	Uncertain significance	criteria provided, multiple submitters, no conflicts
287331	NM_017668.3(NDE1):c.302C>T (p.Ala101Val)	NDE1	Uncertain significance	criteria provided, multiple submitters, no conflicts
435935	NM_017668.3(NDE1):c.701G>A (p.Arg234His)	NDE1	Uncertain significance	criteria provided, multiple submitters, no conflicts

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	Supportive	Autosomal recessive	NDE1-related microhydranencephaly	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,clinvar

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.