Bilateral parasagittal parieto-occipital polymicrogyria

Summary

Bilateral parasagittal parieto-occipital polymicrogyria (MONDO:0012986) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 31
• Phenotypes (HPO): 29

Clinical features

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0002194	Delayed gross motor development	Very frequent (80-99%)
HP:0002539	Cortical dysplasia	Very frequent (80-99%)
HP:0010862	Delayed fine motor development	Very frequent (80-99%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0002069	Bilateral tonic-clonic seizure	Frequent (30-79%)
HP:0000174	Abnormal palate morphology	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000951	Abnormality of the skin	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001345	Psychotic mentation	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002367	Visual hallucinations	Occasional (5-29%)
HP:0002384	Focal impaired awareness seizure	Occasional (5-29%)
HP:0007024	Pseudobulbar paralysis	Occasional (5-29%)
HP:0008765	Auditory hallucinations	Occasional (5-29%)
HP:0011297	Abnormal digit morphology	Occasional (5-29%)
HP:0031258	Delirium	Occasional (5-29%)
HP:0031589	Suicidal ideation	Occasional (5-29%)
HP:0100852	Abnormal fear/anxiety-related behavior	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bilateral parasagittal parieto-occipital polymicrogyria
Mondo ID	MONDO:0012986
MeSH	C567201
OMIM	612691
Orphanet	208441
DOID	DOID:0080923
ICD-11	293410499
UMLS	C4013648
MedGen	862085
GARD	0010785
Is cancer (heuristic)	no

Also known as: BTOP · polymicrogyria, bilateral temporooccipital

Data availability: 31 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › polymicrogyria › bilateral polymicrogyria › bilateral parasagittal parieto-occipital polymicrogyria

Related subtypes (4): bilateral frontoparietal polymicrogyria, bilateral generalized polymicrogyria, bilateral frontal polymicrogyria, bilateral perisylvian 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

31 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 6 benign, 5 pathogenic, 4 benign/likely benign, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1721	NM_014845.6(FIG4):c.122T>C (p.Ile41Thr)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1940123	NM_014845.6(FIG4):c.1808_1811dup (p.Pro605fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
420149	NM_014845.6(FIG4):c.737G>A (p.Trp246Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
50995	NM_014845.6(FIG4):c.831_838del (p.Lys278fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
638361	NM_014845.6(FIG4):c.290-2A>G	FIG4	Pathogenic	criteria provided, single submitter
916868	NM_014845.6(FIG4):c.2247dup (p.Ser750fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
3382272	NM_014845.6(FIG4):c.1389-2A>G	FIG4	Likely pathogenic	criteria provided, single submitter
3892147	NM_014845.6(FIG4):c.1150A>T (p.Arg384Ter)	FIG4	Likely pathogenic	criteria provided, single submitter
977868	NM_014845.6(FIG4):c.691A>G (p.Asn231Asp)	FIG4	Likely pathogenic	no assertion criteria provided
156015	NM_014845.6(FIG4):c.904G>A (p.Glu302Lys)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
156017	NM_014845.6(FIG4):c.2348A>T (p.Asp783Val)	FIG4	Conflicting classifications of pathogenicity	no assertion criteria provided
407082	NM_014845.6(FIG4):c.834A>T (p.Lys278Asn)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029315	NM_014845.6(FIG4):c.2119G>A (p.Gly707Arg)	FIG4	Uncertain significance	criteria provided, single submitter
1377094	NM_014845.6(FIG4):c.2149A>G (p.Lys717Glu)	FIG4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1733654	NM_014845.6(FIG4):c.365A>G (p.His122Arg)	FIG4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2174531	NM_014845.6(FIG4):c.314A>G (p.Tyr105Cys)	FIG4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585617	NM_014845.6(FIG4):c.504C>G (p.Ser168Arg)	FIG4	Uncertain significance	criteria provided, single submitter
3892150	NM_014845.6(FIG4):c.31T>G (p.Ser11Ala)	FIG4	Uncertain significance	criteria provided, single submitter
585870	NM_014845.6(FIG4):c.2360G>A (p.Ser787Asn)	FIG4	Uncertain significance	criteria provided, multiple submitters, no conflicts
804806	NM_014845.6(FIG4):c.2444T>C (p.Phe815Ser)	FIG4	Uncertain significance	criteria provided, multiple submitters, no conflicts
137376	NM_014845.6(FIG4):c.27C>T (p.Ile9=)	FIG4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
137377	NM_014845.6(FIG4):c.1961T>C (p.Val654Ala)	FIG4	Benign	criteria provided, multiple submitters, no conflicts
260447	NM_014845.6(FIG4):c.1948+3A>G	FIG4	Benign	criteria provided, multiple submitters, no conflicts
260449	NM_014845.6(FIG4):c.2559G>A (p.Ser853=)	FIG4	Benign	criteria provided, multiple submitters, no conflicts
260450	NM_014845.6(FIG4):c.447-16G>T	FIG4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
355038	NM_014845.6(FIG4):c.1242T>C (p.Ile414=)	FIG4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
673596	NM_014845.6(FIG4):c.1948+46C>A	FIG4	Benign	criteria provided, multiple submitters, no conflicts
694980	NM_014845.6(FIG4):c.447-3dup	FIG4	Benign	criteria provided, multiple submitters, no conflicts
917077	NM_014845.6(FIG4):c.447-16delinsTT	FIG4	Likely benign	criteria provided, multiple submitters, no conflicts
917083	NM_014845.6(FIG4):c.447-17dup	FIG4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 4 · 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
FIG4	Moderate	Autosomal recessive	bilateral parasagittal parieto-occipital polymicrogyria	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FIG4	Orphanet:139515	Charcot-Marie-Tooth disease type 4J
FIG4	Orphanet:208441	Bilateral parasagittal parieto-occipital polymicrogyria
FIG4	Orphanet:3472	Yunis-Varon syndrome
FIG4	Orphanet:803	Amyotrophic lateral sclerosis

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
FIG4	HGNC:16873	ENSG00000112367	Q92562	Polyphosphoinositide phosphatase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FIG4	Polyphosphoinositide phosphatase	Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).

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)
FIG4	Other/Unknown	no		SAC_dom, Fig4-like

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
endothelial cell	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FIG4	295	ubiquitous	marker	middle temporal gyrus, endothelial cell, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FIG4	1,257

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FIG4	Q92562	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Synthesis of PIPs at the late endosome membrane	1	951.7×	0.002	FIG4
Synthesis of PIPs at the early endosome membrane	1	713.8×	0.002	FIG4
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.002	FIG4

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
negative regulation of myelination	1	1872.4×	0.002	FIG4
myelin assembly	1	1872.4×	0.002	FIG4
vacuole organization	1	1532.0×	0.002	FIG4
pigmentation	1	702.2×	0.003	FIG4
phosphatidylinositol dephosphorylation	1	648.1×	0.003	FIG4
phosphatidylinositol biosynthetic process	1	366.4×	0.004	FIG4
neuron development	1	255.3×	0.005	FIG4
locomotory behavior	1	179.3×	0.006	FIG4
positive regulation of neuron projection development	1	137.0×	0.007	FIG4

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
FIG4	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	FIG4

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)
FIG4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.