Pelizaeus-Merzbacher disease in female carriers

Summary

Pelizaeus-Merzbacher disease in female carriers (MONDO:0017224) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• Phenotypes (HPO): 28

Clinical features

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000011	Neurogenic bladder	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000666	Horizontal nystagmus	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001268	Mental deterioration	Occasional (5-29%)
HP:0001273	Abnormal corpus callosum morphology	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0002061	Lower limb spasticity	Occasional (5-29%)
HP:0002167	Abnormality of speech or vocalization	Occasional (5-29%)
HP:0002197	Generalized-onset seizure	Occasional (5-29%)
HP:0002313	Spastic paraparesis	Occasional (5-29%)
HP:0002376	Developmental regression	Occasional (5-29%)
HP:0002540	Inability to walk	Occasional (5-29%)
HP:0003429	CNS hypomyelination	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0007413	Nevus flammeus of the forehead	Occasional (5-29%)
HP:0010936	Abnormality of the lower urinary tract	Occasional (5-29%)
HP:0011342	Mild global developmental delay	Occasional (5-29%)
HP:0011343	Moderate global developmental delay	Occasional (5-29%)
HP:0011800	Midface retrusion	Occasional (5-29%)
HP:0030784	Anomia	Occasional (5-29%)
HP:0030890	Hyperintensity of cerebral white matter on MRI	Occasional (5-29%)
HP:0032044	Decreased vigilance	Occasional (5-29%)
HP:0032588	Hand apraxia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Pelizaeus-Merzbacher disease in female carriers
Mondo ID	MONDO:0017224
Orphanet	280229
ICD-11	1751389523
UMLS	C5438815
MedGen	1753109
GARD	0021075
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › Pelizaeus-Merzbacher spectrum disorder › Pelizaeus-Merzbacher disease in female carriers

Related subtypes (4): Pelizaeus-Merzbacher disease, connatal form, Pelizaeus-Merzbacher disease, classic form, Pelizaeus-Merzbacher disease, transitional form, null syndrome

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: 13 · Orphanet: 7 · 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
PLP1	Definitive	X-linked	Pelizaeus-Merzbacher spectrum disorder	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLP1	Orphanet:280210	Pelizaeus-Merzbacher disease, connatal form
PLP1	Orphanet:280219	Pelizaeus-Merzbacher disease, classic form
PLP1	Orphanet:280224	Pelizaeus-Merzbacher disease, transitional form
PLP1	Orphanet:280229	Pelizaeus-Merzbacher disease in female carriers
PLP1	Orphanet:280234	Null syndrome
PLP1	Orphanet:599376	Hypomyelination of early myelinating structures
PLP1	Orphanet:99015	Spastic paraplegia type 2

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
PLP1	HGNC:9086	ENSG00000123560	P60201	Myelin proteolipid protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLP1	Myelin proteolipid protein	This is the major myelin protein from the central nervous system.

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)
PLP1	Other/Unknown	no		Myelin_PLP, Myelin_PLP_CS

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
corpus callosum	1
inferior vagus X ganglion	1
middle frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLP1	250	broad	marker	corpus callosum, middle frontal gyrus, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLP1	157

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLP1	P60201	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
axon ensheathment	1	2808.7×	0.003	PLP1
astrocyte development	1	1123.5×	0.003	PLP1
central nervous system myelination	1	991.3×	0.003	PLP1
axon development	1	455.5×	0.004	PLP1
long-chain fatty acid biosynthetic process	1	443.5×	0.004	PLP1
substantia nigra development	1	366.4×	0.004	PLP1
chemical synaptic transmission	1	77.3×	0.017	PLP1
positive regulation of gene expression	1	38.7×	0.027	PLP1
inflammatory response	1	37.7×	0.027	PLP1

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
PLP1	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	PLP1

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)
PLP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.