X-linked Opitz G/BBB syndrome

Summary

X-linked Opitz G/BBB syndrome (MONDO:0010222) is a disease caused by MID1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MID1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 66

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked Opitz G/BBB syndrome
Mondo ID	MONDO:0010222
OMIM	300000
Orphanet	306597
UMLS	C2936904
MedGen	424842
GARD	0024713
NORD	1868
Is cancer (heuristic)	no

Also known as: GBBB1 · Opitz Bbbg syndrome, type 1 · Opitz G/BBB syndrome, X-linked · Opitz GBBB syndrome, type 1 · Opitz GBBB syndrome, type I · Opitz GBBB syndrome, type I, X-linked recessive · Opitz-G syndrome, type 1 · X-linked Opitz BBB/G syndrome · X-linked Opitz G/BBB syndrome · X-linked Opitz syndrome · XLOS

Data availability: 66 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › X-linked Opitz G/BBB syndrome

Related subtypes (49): X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

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

66 retrieved; paginated sample, class counts are floors:

21 pathogenic, 18 likely pathogenic, 16 uncertain significance, 7 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4056381	NM_000381.4(MID1):c.1667G>A (p.Gly556Asp)	LOC126863207	Pathogenic	criteria provided, single submitter
10805	NM_000381.4(MID1):c.1311GAT[1] (p.Met438del)	MID1	Pathogenic	no assertion criteria provided
10807	NM_000381.4(MID1):c.1558dup (p.Glu520fs)	MID1	Pathogenic	no assertion criteria provided
10808	NM_000381.4(MID1):c.1877T>C (p.Leu626Pro)	MID1	Pathogenic	no assertion criteria provided
10809	NM_000381.4(MID1):c.343G>T (p.Glu115Ter)	MID1	Pathogenic	no assertion criteria provided
10810	NG_008197.2:g.(218402_271087)_(271804_315503)dup	MID1	Pathogenic	no assertion criteria provided
10811	NM_000381.4(MID1):c.884T>C (p.Leu295Pro)	MID1	Pathogenic	no assertion criteria provided
10812	NM_000381.4(MID1):c.1546_1547del (p.Thr518_Pro519insTer)	MID1	Pathogenic	criteria provided, single submitter
1684290	NM_000381.4(MID1):c.673_674del (p.Glu224_Ser225insTer)	MID1	Pathogenic	criteria provided, single submitter
1702864	NM_000381.4(MID1):c.1102C>T (p.Arg368Ter)	MID1	Pathogenic	criteria provided, multiple submitters, no conflicts
198721	NM_000381.4(MID1):c.1444_1447dup (p.Ser483fs)	MID1	Pathogenic	criteria provided, multiple submitters, no conflicts
29975	NM_000381.4(MID1):c.712G>T (p.Glu238Ter)	MID1	Pathogenic	no assertion criteria provided
3235986	NM_000381.4(MID1):c.671_674del (p.Glu224fs)	MID1	Pathogenic	criteria provided, single submitter
3395997	NM_000381.4(MID1):c.1554_1555del (p.Thr518_Pro519insTer)	MID1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4082029	NM_000381.4(MID1):c.1313_1316dup (p.Val440fs)	MID1	Pathogenic	no assertion criteria provided
523781	NM_000381.4(MID1):c.1483C>T (p.Arg495Ter)	MID1	Pathogenic	criteria provided, multiple submitters, no conflicts
547520	NM_000381.4(MID1):c.757-1G>C	MID1	Pathogenic	criteria provided, single submitter
547521	NM_000381.4(MID1):c.829C>T (p.Arg277Ter)	MID1	Pathogenic	criteria provided, multiple submitters, no conflicts
547523	NM_000381.4(MID1):c.1393G>C (p.Ala465Pro)	MID1	Pathogenic	criteria provided, single submitter
547525	NM_000381.4(MID1):c.1608_1611dup (p.Ser538Ter)	MID1	Pathogenic	criteria provided, single submitter
617627	NM_000381.4(MID1):c.1917del (p.Thr640fs)	MID1	Pathogenic	no assertion criteria provided
92876	NM_000381.4(MID1):c.1798dup (p.His600fs)	MID1	Pathogenic	criteria provided, multiple submitters, no conflicts
973281	NM_000381.4(MID1):c.388G>A (p.Ala130Thr)	MID1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299558	NM_000381.4(MID1):c.1924A>C (p.Thr642Pro)	LOC126863207	Likely pathogenic	criteria provided, single submitter
2443310	NM_000381.4(MID1):c.1798del (p.His600fs)	LOC126863207	Likely pathogenic	criteria provided, single submitter
3256591	NM_000381.4(MID1):c.1814G>T (p.Gly605Val)	LOC126863207	Likely pathogenic	criteria provided, single submitter
547527	NM_000381.4(MID1):c.1725G>A (p.Trp575Ter)	LOC126863207	Likely pathogenic	criteria provided, single submitter
1175196	NM_000381.4(MID1):c.1863_1879dup (p.Tyr627Ter)	MID1	Likely pathogenic	criteria provided, single submitter
1302010	NM_000381.4(MID1):c.757-1G>A	MID1	Likely pathogenic	criteria provided, single submitter
1333357	NM_000381.4(MID1):c.1310G>A (p.Trp437Ter)	MID1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MID1	Definitive	X-linked	X-linked Opitz G/BBB syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MID1	Orphanet:2745	Opitz GBBB syndrome

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
MID1	HGNC:7095	ENSG00000101871	O15344	E3 ubiquitin-protein ligase Midline-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MID1	E3 ubiquitin-protein ligase Midline-1	Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.

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)
MID1	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY

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
cervix squamous epithelium	1
mucosa of paranasal sinus	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MID1	283	ubiquitous	marker	mucosa of paranasal sinus, ventricular zone, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MID1	1,161

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MID1	O15344	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
Interferon gamma signaling	1	125.5×	0.008	MID1

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
protein localization to microtubule	1	1296.3×	0.003	MID1
positive regulation of stress-activated MAPK cascade	1	802.5×	0.003	MID1
regulation of microtubule cytoskeleton organization	1	543.6×	0.003	MID1
negative regulation of microtubule depolymerization	1	495.6×	0.003	MID1
pattern specification process	1	468.1×	0.003	MID1
microtubule cytoskeleton organization	1	121.2×	0.008	MID1

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
MID1	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	MID1

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)
MID1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.