Diencephalic-mesencephalic junction dysplasia syndrome 2

Summary

Diencephalic-mesencephalic junction dysplasia syndrome 2 (MONDO:0020762) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diencephalic-mesencephalic junction dysplasia syndrome 2
Mondo ID	MONDO:0020762
OMIM	618646
UMLS	C5231440
MedGen	1684846
GARD	0025240
Is cancer (heuristic)	no

Also known as: DMJDS2

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › diencephalic-mesencephalic junction dysplasia › diencephalic-mesencephalic junction dysplasia syndrome 2

Related subtypes (1): diencephalic-mesencephalic junction dysplasia syndrome 1

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

5 retrieved; paginated sample, class counts are floors:

3 benign, 2 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
694062	NM_133267.3(GSX2):c.26C>A (p.Ser9Ter)	GSX2	no classifications from unflagged records	no classifications from unflagged records
694063	NM_133267.3(GSX2):c.752A>G (p.Gln251Arg)	GSX2	no classifications from unflagged records	no classifications from unflagged records
1182813	NM_133267.3(GSX2):c.156C>T (p.Ser52=)	GSX2	Benign	criteria provided, multiple submitters, no conflicts
1223318	NM_133267.3(GSX2):c.408T>C (p.His136=)	GSX2	Benign	criteria provided, multiple submitters, no conflicts
1285310	NM_133267.3(GSX2):c.319G>A (p.Gly107Ser)	GSX2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
GSX2	Moderate	Autosomal recessive	diencephalic-mesencephalic junction dysplasia syndrome 2	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GSX2	Orphanet:319192	Diencephalic-mesencephalic junction dysplasia

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
GSX2	HGNC:24959	ENSG00000180613	Q9BZM3	GS homeobox 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GSX2	GS homeobox 2	Transcription factor that binds 5’-CNAATTAG-3’ DNA sequence and regulates the expression of numerous genes including genes important for brain development.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GSX2	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_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
amygdala	1
secondary oocyte	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GSX2	58	tissue_specific	marker	secondary oocyte, amygdala, superficial temporal artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GSX2	786

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GSX2	Q9BZM3	61.18

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
subpallium neuron fate commitment	1	8426.0×	1e-03	GSX2
hindbrain morphogenesis	1	4213.0×	1e-03	GSX2
olfactory bulb interneuron differentiation	1	3370.4×	1e-03	GSX2
GABAergic neuron differentiation	1	3370.4×	1e-03	GSX2
telencephalon regionalization	1	2808.7×	1e-03	GSX2
forebrain dorsal/ventral pattern formation	1	2106.5×	0.001	GSX2
forebrain morphogenesis	1	1404.3×	0.001	GSX2
regulation of respiratory gaseous exchange by nervous system process	1	1296.3×	0.001	GSX2
spinal cord association neuron differentiation	1	1296.3×	0.001	GSX2
neuron fate specification	1	702.2×	0.002	GSX2
positive regulation of oligodendrocyte differentiation	1	674.1×	0.002	GSX2
positive regulation of Notch signaling pathway	1	351.1×	0.003	GSX2
regulation of cell migration	1	157.5×	0.007	GSX2
Notch signaling pathway	1	141.6×	0.007	GSX2

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
GSX2	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	GSX2

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)
GSX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.