Polymicrogyria with optic nerve hypoplasia

disease

On this page

Also known as CDCBM8

Summary

Polymicrogyria with optic nerve hypoplasia (MONDO:0013172) is a disease with 1 cohort gene.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Cohort genes: 1
ClinVar variants: 8
Phenotypes (HPO): 14

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0000609	Optic nerve hypoplasia	Very frequent (80-99%)
HP:0000707	Abnormality of the nervous system	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001265	Hyporeflexia	Very frequent (80-99%)
HP:0001319	Neonatal hypotonia	Very frequent (80-99%)
HP:0001344	Absent speech	Very frequent (80-99%)
HP:0002126	Polymicrogyria	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0030048	Colpocephaly	Very frequent (80-99%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0002069	Bilateral tonic-clonic seizure	Frequent (30-79%)
HP:0002365	Hypoplasia of the brainstem	Occasional (5-29%)
HP:0006989	Dysplastic corpus callosum	Occasional (5-29%)
HP:0012469	Infantile spasms	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	polymicrogyria with optic nerve hypoplasia
Mondo ID	MONDO:0013172
MeSH	C567715
OMIM	613180
Orphanet	250972
UMLS	C2750798
MedGen	442565
GARD	0020687
Is cancer (heuristic)	no

Also known as: CDCBM8 · polymicrogyria with optic nerve hypoplasia

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › complex cortical dysplasia with other brain malformations › polymicrogyria with optic nerve hypoplasia

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

8 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
160175	NM_018943.3(TUBA8):c.958C>T (p.Arg320Trp)	TUBA8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425280	NM_018943.3(TUBA8):c.967G>A (p.Val323Met)	TUBA8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033914	NM_018943.3(TUBA8):c.5G>A (p.Arg2Gln)	TUBA8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033915	NM_018943.3(TUBA8):c.727C>T (p.Arg243Cys)	TUBA8	Uncertain significance	criteria provided, multiple submitters, no conflicts
448843	NM_018943.3(TUBA8):c.1117C>T (p.Arg373Trp)	TUBA8	Uncertain significance	criteria provided, multiple submitters, no conflicts
4782	NM_018943.3(TUBA8):c.4-21_4-8del	TUBA8	Uncertain significance	no assertion criteria provided
562019	NM_018943.3(TUBA8):c.661C>T (p.Arg221Cys)	TUBA8	Uncertain significance	criteria provided, single submitter
592146	NM_018943.3(TUBA8):c.728G>A (p.Arg243His)	TUBA8	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
TUBA8	Supportive	Autosomal recessive	polymicrogyria with optic nerve hypoplasia	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBA8	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TUBA8	Orphanet:250972	Polymicrogyria with optic nerve hypoplasia

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
TUBA8	HGNC:12410	ENSG00000183785	Q9NY65	Tubulin alpha-8 chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBA8	Tubulin alpha-8 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

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)
TUBA8	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase

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
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBA8	135	broad	marker	hindlimb stylopod muscle, gastrocnemius, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBA8	4,465

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBA8	Q9NY65	91.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.017	TUBA8
Transport of connexons to the plasma membrane	1	543.8×	0.017	TUBA8
Gap junction trafficking and regulation	1	475.8×	0.017	TUBA8
Gap junction trafficking	1	475.8×	0.017	TUBA8
Post-chaperonin tubulin folding pathway	1	475.8×	0.017	TUBA8
Formation of tubulin folding intermediates by CCT/TriC	1	423.0×	0.017	TUBA8
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.017	TUBA8
Activation of AMPK downstream of NMDARs	1	380.7×	0.017	TUBA8
RHO GTPases activate IQGAPs	1	346.1×	0.017	TUBA8
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.017	TUBA8
HCMV Infection	1	326.3×	0.017	TUBA8
Chaperonin-mediated protein folding	1	300.5×	0.017	TUBA8
Gap junction assembly	1	292.8×	0.017	TUBA8
Nuclear Envelope (NE) Reassembly	1	292.8×	0.017	TUBA8
Selective autophagy	1	278.5×	0.017	TUBA8
Protein folding	1	259.6×	0.017	TUBA8
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.017	TUBA8
Cargo trafficking to the periciliary membrane	1	248.3×	0.017	TUBA8
Aggrephagy	1	248.3×	0.017	TUBA8
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.017	TUBA8
Recycling pathway of L1	1	223.9×	0.017	TUBA8
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.017	TUBA8
Post NMDA receptor activation events	1	203.9×	0.017	TUBA8
Antimicrobial mechanism of IFN-stimulated genes	1	196.9×	0.017	TUBA8
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.017	TUBA8
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.017	TUBA8
Kinesins	1	178.4×	0.017	TUBA8
The role of GTSE1 in G2/M progression after G2 checkpoint	1	160.8×	0.018	TUBA8
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	154.3×	0.018	TUBA8
Autophagy	1	148.3×	0.018	TUBA8

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
spermatid development	1	145.3×	0.008	TUBA8
mitotic cell cycle	1	133.8×	0.008	TUBA8
microtubule cytoskeleton organization	1	121.2×	0.008	TUBA8

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBA8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TUBA8	73	Binding:72, Functional:1

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	TUBA8

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)
TUBA8	73	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TUBA8