Polymicrogyria, bilateral perisylvian, autosomal recessive

Summary

Polymicrogyria, bilateral perisylvian, autosomal recessive (MONDO:0014333) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polymicrogyria, bilateral perisylvian, autosomal recessive
Mondo ID	MONDO:0014333
OMIM	615752
UMLS	C3810405
MedGen	816735
GARD	0016009
Is cancer (heuristic)	no

Also known as: BPPR · polymicrogyria, bilateral perisylvian · polymicrogyria, bilateral perisylvian, autosomal recessive

Data availability: 27 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › polymicrogyria › bilateral polymicrogyria › bilateral perisylvian polymicrogyria › polymicrogyria, bilateral perisylvian, autosomal recessive

Related subtypes (2): polymicrogyria, bilateral perisylvian, X-linked, polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

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

27 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
127079	NM_201525.4(ADGRG1):c.-36+10587_-36+10601del	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451570	NM_201525.4(ADGRG1):c.531C>A (p.Cys177Ter)	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158618	NM_201525.4(ADGRG1):c.1408C>T (p.Arg470Ter)	ADGRG1	Pathogenic	criteria provided, multiple submitters, no conflicts
158629	NM_201525.4(ADGRG1):c.286C>T (p.Arg96Ter)	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372729	NM_201525.4(ADGRG1):c.671del (p.Asp224fs)	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430049	NM_201525.4(ADGRG1):c.235C>T (p.Arg79Ter)	ADGRG1	Pathogenic	criteria provided, multiple submitters, no conflicts
5828	NM_201525.4(ADGRG1):c.739_745del (p.Gln247fs)	ADGRG1	Pathogenic	criteria provided, multiple submitters, no conflicts
620113	NM_201525.4(ADGRG1):c.811C>T (p.Arg271Ter)	ADGRG1	Pathogenic	criteria provided, multiple submitters, no conflicts
662811	NM_201525.4(ADGRG1):c.407T>A (p.Leu136Ter)	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
934237	NM_201525.4(ADGRG1):c.215del (p.Pro72fs)	ADGRG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1878521	NM_201525.4(ADGRG1):c.1010dup (p.Gln338fs)	ADGRG1	Likely pathogenic	criteria provided, single submitter
3014721	NM_201525.4(ADGRG1):c.488-2A>G	ADGRG1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3581088	NM_201525.4(ADGRG1):c.264C>A (p.Tyr88Ter)	ADGRG1	Likely pathogenic	criteria provided, single submitter
3581089	NM_201525.4(ADGRG1):c.581_584dup (p.Ala196fs)	ADGRG1	Likely pathogenic	criteria provided, single submitter
3581091	NM_201525.4(ADGRG1):c.1000C>T (p.Gln334Ter)	ADGRG1	Likely pathogenic	criteria provided, single submitter
3581092	NM_201525.4(ADGRG1):c.1063+1G>A	ADGRG1	Likely pathogenic	criteria provided, single submitter
3581093	NM_201525.4(ADGRG1):c.1254C>A (p.Cys418Ter)	ADGRG1	Likely pathogenic	criteria provided, single submitter
1034203	NM_201525.4(ADGRG1):c.620+11C>T	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158620	NM_201525.4(ADGRG1):c.1490T>C (p.Leu497Pro)	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
372698	NM_201525.4(ADGRG1):c.843_844delinsGC (p.Ser281_Gly282delinsArgArg)	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5829	NM_201525.4(ADGRG1):c.112C>T (p.Arg38Trp)	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
585950	NM_201525.4(ADGRG1):c.26C>T (p.Thr9Met)	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632548	NM_201525.4(ADGRG1):c.391C>T (p.Gln131Ter)	ADGRG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3581094	NM_201525.4(ADGRG1):c.1807G>A (p.Val603Met)	ADGRG1	Uncertain significance	criteria provided, single submitter
435357	NM_201525.4(ADGRG1):c.1775G>A (p.Arg592Gln)	ADGRG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
988720	NM_201525.4(ADGRG1):c.1561C>G (p.Pro521Ala)	ADGRG1	Uncertain significance	no assertion criteria provided
158638	NM_201525.4(ADGRG1):c.844G>C (p.Gly282Arg)	ADGRG1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
ADGRG1	Orphanet:101070	Bilateral frontoparietal polymicrogyria
ADGRG1	Orphanet:98889	Bilateral perisylvian polymicrogyria

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
ADGRG1	HGNC:4512	ENSG00000205336	Q9Y653	Adhesion G-protein coupled receptor G1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADGRG1	Adhesion G-protein coupled receptor G1	Adhesion G-protein coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADGRG1	GPCR	yes		GPS, GPCR_2_secretin-like, GPR1/GPR3/GPR5

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
ganglionic eminence	1
granulocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADGRG1	284	ubiquitous	marker	granulocyte, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADGRG1	1,541

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADGRG1	Q9Y653	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
cerebral cortex radial glia-guided migration	1	4213.0×	0.002	ADGRG1
cerebral cortex regionalization	1	2407.4×	0.002	ADGRG1
regulation of platelet aggregation	1	2407.4×	0.002	ADGRG1
Rho-activating G protein-coupled receptor signaling pathway	1	2407.4×	0.002	ADGRG1
negative regulation of neuron migration	1	1404.3×	0.003	ADGRG1
layer formation in cerebral cortex	1	1123.5×	0.003	ADGRG1
positive regulation of vascular endothelial growth factor signaling pathway	1	1123.5×	0.003	ADGRG1
negative regulation of ferroptosis	1	802.5×	0.003	ADGRG1
seminiferous tubule development	1	766.0×	0.003	ADGRG1
positive regulation of neural precursor cell proliferation	1	766.0×	0.003	ADGRG1
neural precursor cell proliferation	1	674.1×	0.003	ADGRG1
positive regulation of Rho protein signal transduction	1	581.1×	0.003	ADGRG1
hematopoietic stem cell homeostasis	1	561.7×	0.003	ADGRG1
positive regulation of cell adhesion	1	271.8×	0.006	ADGRG1
Rho protein signal transduction	1	247.8×	0.006	ADGRG1
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.011	ADGRG1
brain development	1	79.5×	0.018	ADGRG1
cell-cell signaling	1	69.6×	0.019	ADGRG1
cell surface receptor signaling pathway	1	64.1×	0.019	ADGRG1
angiogenesis	1	62.4×	0.019	ADGRG1
cell migration	1	61.5×	0.019	ADGRG1
negative regulation of cell population proliferation	1	42.1×	0.026	ADGRG1
cell adhesion	1	37.5×	0.028	ADGRG1
G protein-coupled receptor signaling pathway	1	36.2×	0.028	ADGRG1

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
ADGRG1	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
ADGRG1	3	Binding:3

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	ADGRG1
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)
ADGRG1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.