Unilateral polymicrogyria

Summary

Unilateral polymicrogyria (MONDO:0017092) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 37

Clinical features

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001269	Hemiparesis	Frequent (30-79%)
HP:0002510	Spastic tetraplegia	Frequent (30-79%)
HP:0002539	Cortical dysplasia	Frequent (30-79%)
HP:0007010	Poor fine motor coordination	Frequent (30-79%)
HP:0007024	Pseudobulbar paralysis	Frequent (30-79%)
HP:0010818	Generalized tonic seizure	Frequent (30-79%)
HP:0000421	Epistaxis	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000565	Esotropia	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0000961	Cyanosis	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001312	Giant somatosensory evoked potentials	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002133	Status epilepticus	Occasional (5-29%)
HP:0002384	Focal impaired awareness seizure	Occasional (5-29%)
HP:0002421	Poor head control	Occasional (5-29%)
HP:0002533	Abnormal posturing	Occasional (5-29%)
HP:0004305	Involuntary movements	Occasional (5-29%)
HP:0006548	Pulmonary arteriovenous malformation	Occasional (5-29%)
HP:0007359	Focal-onset seizure	Occasional (5-29%)
HP:0008610	Infantile sensorineural hearing impairment	Occasional (5-29%)
HP:0008936	Axial hypotonia	Occasional (5-29%)
HP:0011344	Severe global developmental delay	Occasional (5-29%)
HP:0012389	Appendicular hypotonia	Occasional (5-29%)
HP:0012469	Infantile spasms	Occasional (5-29%)
HP:0012650	Perisylvian polymicrogyria	Occasional (5-29%)
HP:0000252	Microcephaly	Very rare (<1-4%)
HP:0001335	Bimanual synkinesia	Very rare (<1-4%)
HP:0001627	Abnormal heart morphology	Very rare (<1-4%)
HP:0040288	Nasogastric tube feeding	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	unilateral polymicrogyria
Mondo ID	MONDO:0017092
Orphanet	268943
ICD-11	782302128
SNOMED CT	715905006
UMLS	C4024960
MedGen	870513
GARD	0020980
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › polymicrogyria › unilateral polymicrogyria

Related subtypes (1): bilateral polymicrogyria

Subtypes (2): unilateral hemispheric polymicrogyria, unilateral focal polymicrogyria

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
523516	NM_015922.3(NSDHL):c.790-5G>T	NSDHL	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NSDHL	Orphanet:139	CHILD syndrome
NSDHL	Orphanet:251383	CK syndrome

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
NSDHL	HGNC:13398	ENSG00000147383	Q15738	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSDHL	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NSDHL	Enzyme (other)	yes	1.1.1.170	3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, Lipid_A_modif_metabolic_enz

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
adrenal tissue	1
cervix squamous epithelium	1
esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSDHL	271	ubiquitous	marker	cervix squamous epithelium, adrenal tissue, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSDHL	3,566

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NSDHL	Q15738	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	1268.9×	9e-04	NSDHL
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	1142.0×	9e-04	NSDHL

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
obsolete cholesterol biosynthetic process via lathosterol	1	2106.5×	0.003	NSDHL
labyrinthine layer blood vessel development	1	802.5×	0.004	NSDHL
cholesterol biosynthetic process	1	421.3×	0.004	NSDHL
hair follicle development	1	383.0×	0.004	NSDHL
cholesterol metabolic process	1	195.9×	0.006	NSDHL
smoothened signaling pathway	1	181.2×	0.006	NSDHL

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
NSDHL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSDHL	1.1.1.170	3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating)

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	1	NSDHL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
NSDHL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.