intellectual developmental disorder, X-linked, syndromic, Pilorge type

Summary

intellectual developmental disorder, X-linked, syndromic, Pilorge type (MONDO:0024772) is a disease caused by GLRA2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: GLRA2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, X-linked, syndromic, Pilorge type
Mondo ID	MONDO:0024772
OMIM	301076
DOID	DOID:0070422
UMLS	C5676881
MedGen	1803486
GARD	0025464
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked, syndromic, Pilorge type · MRXSP

Data availability: 20 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › X-linked syndromic intellectual disability › intellectual developmental disorder, X-linked, syndromic, Pilorge type

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Renpenning syndrome, Partington syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Wilson-Turner syndrome, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, intellectual developmental disorder, X-linked, syndromic 37, CASK-related intellectual disability

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

20 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 5 pathogenic, 3 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686860	NM_002063.4(GLRA2):c.1049G>T (p.Arg350Leu)	FANCB	Pathogenic	no assertion criteria provided
1686857	NM_002063.4(GLRA2):c.407A>G (p.Asn136Ser)	GLRA2	Pathogenic	no assertion criteria provided
1686858	NC_000023.10:g.14693216_14836199del	GLRA2	Pathogenic	no assertion criteria provided
1686859	NM_002063.4(GLRA2):c.458G>A (p.Arg153Gln)	GLRA2	Pathogenic	no assertion criteria provided
810510	NM_002063.4(GLRA2):c.887C>T (p.Thr296Met)	GLRA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1334408	NM_002063.4(GLRA2):c.777C>G (p.Ile259Met)	GLRA2	Likely pathogenic	criteria provided, single submitter
4536752	NM_002063.4(GLRA2):c.494G>C (p.Arg165Thr)	GLRA2	Likely pathogenic	criteria provided, single submitter
4755488	NM_002063.4(GLRA2):c.392A>G (p.Asp131Gly)	GLRA2	Likely pathogenic	criteria provided, single submitter
1334406	NM_002063.4(GLRA2):c.1186C>A (p.Pro396Thr)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705404	NM_002063.4(GLRA2):c.1048C>T (p.Arg350Cys)	FANCB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242020	NM_002063.4(GLRA2):c.1108T>C (p.Phe370Leu)	FANCB	Uncertain significance	criteria provided, single submitter
3383176	NM_002063.4(GLRA2):c.1025C>G (p.Ser342Cys)	FANCB	Uncertain significance	criteria provided, single submitter
4056498	NM_002063.4(GLRA2):c.1237G>C (p.Asp413His)	FANCB	Uncertain significance	criteria provided, single submitter
4078788	NM_002063.4(GLRA2):c.950T>C (p.Ile317Thr)	FANCB	Uncertain significance	criteria provided, single submitter
4532161	NM_002063.4(GLRA2):c.1054C>T (p.Arg352Ter)	FANCB	Uncertain significance	criteria provided, single submitter
1334405	NM_002063.4(GLRA2):c.754C>T (p.Arg252Cys)	GLRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2674608	NM_002063.4(GLRA2):c.659A>C (p.Gln220Pro)	GLRA2	Uncertain significance	criteria provided, single submitter
3366873	NM_002063.4(GLRA2):c.640G>C (p.Glu214Gln)	GLRA2	Uncertain significance	criteria provided, single submitter
4072301	NM_002063.4(GLRA2):c.270+143T>G	GLRA2	Uncertain significance	criteria provided, single submitter
4292643	NM_002063.4(GLRA2):c.774G>C (p.Leu258Phe)	GLRA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
GLRA2	Strong	X-linked	intellectual developmental disorder, X-linked, syndromic, Pilorge type	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FANCB	Orphanet:3412	VACTERL with hydrocephalus
FANCB	Orphanet:84	Fanconi anemia

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
GLRA2	HGNC:4327	ENSG00000101958	P23416	Glycine receptor subunit alpha-2	gencc,clinvar
FANCB	HGNC:3583	ENSG00000181544	Q8NB91	Fanconi anemia group B protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLRA2	Glycine receptor subunit alpha-2	Subunit of heteromeric glycine-gated chloride channels.
FANCB	Fanconi anemia group B protein	DNA repair protein required for FANCD2 ubiquitination.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GLRA2	Other/Unknown	no		GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
FANCB	Other/Unknown	no		FANCB

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
cortical plate	1
olfactory bulb	1
type B pancreatic cell	1
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLRA2	75	tissue_specific	marker	cortical plate, type B pancreatic cell, olfactory bulb
FANCB	160	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLRA2	1,193
FANCB	1,097

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GLRA2	P23416	13
FANCB	Q8NB91	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fanconi Anemia Pathway	1	139.3×	0.020	FANCB
PKR-mediated signaling	1	70.5×	0.020	FANCB
Neurotransmitter receptors and postsynaptic signal transmission	1	50.1×	0.020	GLRA2

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
replication-born double-strand break repair via sister chromatid exchange	1	1404.3×	0.008	FANCB
cellular response to ethanol	1	526.6×	0.009	GLRA2
cellular response to zinc ion	1	337.0×	0.009	GLRA2
negative regulation of double-strand break repair via homologous recombination	1	312.1×	0.009	FANCB
interstrand cross-link repair	1	216.1×	0.010	FANCB
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.010	FANCB
cellular response to amino acid stimulus	1	153.2×	0.010	GLRA2
chloride transmembrane transport	1	118.7×	0.012	GLRA2
monoatomic ion transmembrane transport	1	104.0×	0.012	GLRA2
modulation of chemical synaptic transmission	1	91.6×	0.012	GLRA2
neuropeptide signaling pathway	1	86.0×	0.012	GLRA2

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GLRA2	CANNABIDIOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GLRA2	1	4
FANCB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABIDIOL	4	GLRA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GLRA2	5	Binding:3, Functional:2

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
CANNABIDIOL	4	GLRA2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GLRA2
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	FANCB

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)
FANCB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.