polymicrogyria, bilateral perisylvian, X-linked

Summary

polymicrogyria, bilateral perisylvian, X-linked (MONDO:0010314) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polymicrogyria, bilateral perisylvian, X-linked
Mondo ID	MONDO:0010314
OMIM	300388
SNOMED CT	438583008
GARD	0015256
Is cancer (heuristic)	no

Also known as: BPP · BPPX · PMGX · polymicrogyria, bilateral perisylvian, X-linked · polymicrogyria, bilateral perisylvian, X-linked dominant

Data availability: 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 perisylvian polymicrogyria › polymicrogyria, bilateral perisylvian, X-linked

Related subtypes (2): polymicrogyria, bilateral perisylvian, autosomal recessive, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
MCF2	Limited	X-linked	polymicrogyria, bilateral perisylvian, X-linked
SRPX2	Limited	X-linked	rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRPX2	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
SRPX2	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
SRPX2	Orphanet:98889	Bilateral perisylvian polymicrogyria

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
SRPX2	HGNC:30668	ENSG00000102359	O60687	Sushi repeat-containing protein SRPX2	gencc
MCF2	HGNC:6940	ENSG00000101977	P10911	Proto-oncogene DBL	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRPX2	Sushi repeat-containing protein SRPX2	Acts as a ligand for the urokinase plasminogen activator surface receptor.
MCF2	Proto-oncogene DBL	Guanine nucleotide exchange factor (GEF) that modulates the Rho family of GTPases.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · 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
Complement	1	134.0×	0.015
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRPX2	Complement	yes		Sushi_SCR_CCP_dom, HYR_dom, DUF4174
MCF2	Scaffold/PPI	no		DH_dom, CRAL-TRIO_dom, GDS_CDC24_CS

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
calcaneal tendon	1
cartilage tissue	1
stromal cell of endometrium	1
adrenal tissue	1
endothelial cell	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRPX2	211	ubiquitous	marker	stromal cell of endometrium, calcaneal tendon, cartilage tissue
MCF2	191	tissue_specific	marker	adrenal tissue, seminal vesicle, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MCF2	1,039
SRPX2	954

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SRPX2	O60687	86.75
MCF2	P10911	74.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 2 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
p75NTR regulates axonogenesis	1	2284.0×	0.008	MCF2
Axonal growth inhibition (RHOA activation)	1	1268.9×	0.008	MCF2
Cell death signalling via NRAGE, NRIF and NADE	1	219.6×	0.015	MCF2
p75 NTR receptor-mediated signalling	1	187.2×	0.015	MCF2
NRAGE signals death through JNK	1	184.2×	0.015	MCF2
RHOB GTPase cycle	1	154.3×	0.015	MCF2
RHOG GTPase cycle	1	148.3×	0.015	MCF2
RHOC GTPase cycle	1	146.4×	0.015	MCF2
Death Receptor Signaling	1	139.3×	0.015	MCF2
G alpha (12/13) signalling events	1	137.6×	0.015	MCF2
RAC2 GTPase cycle	1	126.9×	0.015	MCF2
RAC3 GTPase cycle	1	119.0×	0.015	MCF2
RHOA GTPase cycle	1	74.6×	0.021	MCF2
CDC42 GTPase cycle	1	72.3×	0.021	MCF2
RAC1 GTPase cycle	1	61.1×	0.022	MCF2
RHO GTPase cycle	1	60.1×	0.022	MCF2
GPCR downstream signalling	1	43.4×	0.028	MCF2
Signaling by GPCR	1	40.1×	0.029	MCF2
Signaling by Rho GTPases	1	34.2×	0.031	MCF2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.031	MCF2
Signal Transduction	1	10.2×	0.098	MCF2

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
regulation of phosphorylation	1	1404.3×	0.008	SRPX2
negative regulation of axonogenesis	1	648.1×	0.008	MCF2
vocalization behavior	1	443.5×	0.008	SRPX2
positive regulation of cell migration involved in sprouting angiogenesis	1	366.4×	0.008	SRPX2
cell motility	1	200.6×	0.010	SRPX2
dendrite development	1	195.9×	0.010	MCF2
positive regulation of synapse assembly	1	122.1×	0.014	SRPX2
cellular response to leukemia inhibitory factor	1	79.5×	0.018	MCF2
regulation of small GTPase mediated signal transduction	1	72.0×	0.018	MCF2
cell-cell adhesion	1	50.8×	0.024	SRPX2
angiogenesis	1	31.2×	0.035	SRPX2
intracellular signal transduction	1	19.1×	0.052	MCF2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRPX2	0	0
MCF2	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
MCF2	1	Binding:1

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	SRPX2
E	Difficult family or no structure, no drug	1	MCF2

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)
SRPX2	0	—
MCF2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.