Hydranencephaly

Summary

Hydranencephaly (MONDO:0016344) is a disease with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000		Worldwide	Validated
Prevalence at birth	1-9 / 100 000	2.1	Japan	Validated
Prevalence at birth	1-9 / 100 000	2.8	United States	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000618	Blindness	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002120	Cerebral cortical atrophy	Very frequent (80-99%)
HP:0008610	Infantile sensorineural hearing impairment	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0010994	Abnormal corpus striatum morphology	Very frequent (80-99%)
HP:0000601	Hypotelorism	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001264	Spastic diplegia	Frequent (30-79%)
HP:0001287	Meningitis	Frequent (30-79%)
HP:0002179	Opisthotonus	Frequent (30-79%)
HP:0006698	Dilatation of the ventricular cavity	Frequent (30-79%)
HP:0007023	Antenatal intracerebral hemorrhage	Frequent (30-79%)
HP:0009145	Abnormal cerebral artery morphology	Frequent (30-79%)
HP:0010652	Abnormal dura mater morphology	Frequent (30-79%)
HP:0011328	Abnormality of fontanelles	Frequent (30-79%)
HP:0025040	Thalamic edema	Frequent (30-79%)
HP:0025099	Dysgenesis of the thalamus	Frequent (30-79%)
HP:0025258	Stiff neck	Frequent (30-79%)
HP:0025517	Hypoplastic hippocampus	Frequent (30-79%)
HP:0410279	Atrophic pituitary gland	Frequent (30-79%)
HP:3000062	Abnormal internal carotid artery morphology	Frequent (30-79%)
HP:0000533	Chorioretinal atrophy	Occasional (5-29%)
HP:0000609	Optic nerve hypoplasia	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0011451	Congenital microcephaly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hydranencephaly
Mondo ID	MONDO:0016344
MeSH	D006832
Orphanet	2177
DOID	DOID:4626
ICD-11	1963574608
NCIT	C98949
SNOMED CT	30023002
UMLS	C0020225
MedGen	6937
GARD	0006681
NORD	1258
Is cancer (heuristic)	no

Also known as: hydranencephaly · hydranencephaly (disease) · Hydroanencephaly

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › anencephaly › hydranencephaly

Related subtypes (3): anencephaly 1, anencephaly 2, isolated anencephaly

Subtypes (1): hemihydranencephaly

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
183290	NM_001163809.2(WDR81):c.845G>A (p.Gly282Glu)	WDR81	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 6 · 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	Strong	Autosomal recessive	microcephaly with lissencephaly and/or hydranencephaly	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
WDR81	Orphanet:1766	Dysequilibrium syndrome
WDR81	Orphanet:269505	Congenital communicating hydrocephalus
WDR81	Orphanet:269510	Congenital non-communicating hydrocephalus

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDE1	HGNC:17619	ENSG00000072864	Q9NXR1	Nuclear distribution protein nudE homolog 1	gencc
WDR81	HGNC:26600	ENSG00000167716	Q562E7	WD repeat-containing protein 81	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.
WDR81	WD repeat-containing protein 81	Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDE1	Other/Unknown	no		NUDE_dom, NUDE
WDR81	Kinase	yes		BEACH_dom, WD40_rpt, Kinase-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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
corpus callosum	1
ventricular zone	1
granulocyte	1
left ovary	1
right ovary	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
WDR81	138	ubiquitous	marker	granulocyte, left ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDE1	1,761
WDR81	1,404

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDE1	Q9NXR1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WDR81	Q562E7	69.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 2 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
Centrosome maturation	1	126.9×	0.037	NDE1
Amplification of signal from the kinetochores	1	98.5×	0.037	NDE1
Loss of Nlp from mitotic centrosomes	1	79.3×	0.037	NDE1
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.037	NDE1
Mitotic Spindle Checkpoint	1	79.3×	0.037	NDE1
AURKA Activation by TPX2	1	76.1×	0.037	NDE1
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.037	NDE1
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.037	NDE1
Mitotic G2-G2/M phases	1	63.4×	0.037	NDE1
G2/M Transition	1	63.4×	0.037	NDE1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	58.3×	0.037	NDE1
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.037	NDE1
Anchoring of the basal body to the plasma membrane	1	56.5×	0.037	NDE1
Cilium Assembly	1	54.4×	0.037	NDE1
Mitotic Metaphase and Anaphase	1	48.4×	0.037	NDE1
Mitotic Anaphase	1	48.4×	0.037	NDE1
EML4 and NUDC in mitotic spindle formation	1	46.4×	0.037	NDE1
Cell Cycle Checkpoints	1	44.3×	0.037	NDE1
Resolution of Sister Chromatid Cohesion	1	43.3×	0.037	NDE1
RHO GTPases Activate Formins	1	38.8×	0.037	NDE1
CDC42 GTPase cycle	1	36.1×	0.037	WDR81
Mitotic Prometaphase	1	34.6×	0.037	NDE1
RHO GTPase Effectors	1	34.0×	0.037	NDE1
Organelle biogenesis and maintenance	1	33.0×	0.037	NDE1
M Phase	1	33.0×	0.037	NDE1
Separation of Sister Chromatids	1	30.4×	0.039	NDE1
Cell Cycle, Mitotic	1	24.1×	0.047	NDE1
Cell Cycle	1	18.0×	0.061	NDE1
Signaling by Rho GTPases	1	17.1×	0.061	NDE1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.061	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 2 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	4213.0×	0.004	NDE1
mitotic centrosome separation	1	1404.3×	0.006	NDE1
aggrephagy	1	842.6×	0.007	WDR81
centrosome duplication	1	468.1×	0.007	NDE1
vesicle transport along microtubule	1	443.5×	0.007	NDE1
centrosome localization	1	443.5×	0.007	NDE1
early endosome to late endosome transport	1	324.1×	0.007	WDR81
microtubule nucleation	1	312.1×	0.007	NDE1
establishment of mitotic spindle orientation	1	240.7×	0.008	NDE1
neuroblast proliferation	1	183.2×	0.010	NDE1
cerebral cortex development	1	102.8×	0.016	NDE1
chromosome segregation	1	86.9×	0.017	NDE1
mitochondrion organization	1	75.9×	0.018	WDR81
neuron migration	1	66.9×	0.019	NDE1
ubiquitin-dependent protein catabolic process	1	37.1×	0.032	WDR81
protein stabilization	1	33.4×	0.033	WDR81
cell migration	1	30.8×	0.034	NDE1
cell division	1	23.1×	0.043	NDE1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
WDR81	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	WDR81
E	Difficult family or no structure, no drug	1	NDE1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NDE1	0	—
WDR81	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.