Microphthalmia, syndromic 2

Summary

Microphthalmia, syndromic 2 (MONDO:0010261) is a disease caused by BCOR (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: BCOR (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 517
• Phenotypes (HPO): 43

Clinical features

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000456	Bifid nasal tip	Very frequent (80-99%)
HP:0000482	Microcornea	Very frequent (80-99%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0000568	Microphthalmia	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Very frequent (80-99%)
HP:0001671	Abnormal cardiac septum morphology	Very frequent (80-99%)
HP:0000174	Abnormal palate morphology	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000176	Submucous cleft hard palate	Frequent (30-79%)
HP:0000275	Narrow face	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000677	Oligodontia	Frequent (30-79%)
HP:0000692	Tooth malposition	Frequent (30-79%)
HP:0001169	Broad palm	Frequent (30-79%)
HP:0001765	Hammertoe	Frequent (30-79%)
HP:0002974	Radioulnar synostosis	Frequent (30-79%)
HP:0004691	2-3 toe syndactyly	Frequent (30-79%)
HP:0010327	Flexion contracture of the 2nd toe	Frequent (30-79%)
HP:0010339	Flexion contracture of the 4th toe	Frequent (30-79%)
HP:0011090	Fused teeth	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000541	Retinal detachment	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0001083	Ectopia lentis	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001634	Mitral valve prolapse	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002857	Genu valgum	Occasional (5-29%)
HP:0002967	Cubitus valgus	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0004969	Peripheral pulmonary artery stenosis	Occasional (5-29%)
HP:0006315	Single median maxillary incisor	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)
HP:0009778	Short thumb	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, syndromic 2
Mondo ID	MONDO:0010261
OMIM	300166
Orphanet	2712
DOID	DOID:0111809
SNOMED CT	699300009
UMLS	C1846265
MedGen	337547
GARD	0004628
Is cancer (heuristic)	no

Also known as: ANOP2 (formerly) · cataract-microphthalmia-radiculomegaly-cardiac septal defect syndrome · MAA2 (formerly) · MCOPS2 · microphthalmia cataracts radiculomegaly and septal heart defects · microphthalmia syndromic 2 · microphthalmia, syndromic 2 · microphthalmia, syndromic 2, X-linked dominant · microphthalmia, syndromic type 2 · oculofaciocardiodental syndrome · OFCD syndrome · syndromic microphthalmia type 2

Data availability: 517 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › microphthalmia, syndromic 2

Related subtypes (18): anophthalmia/microphthalmia-esophageal atresia syndrome, COFS syndrome, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, microphthalmia, syndromic 1, linear skin defects with multiple congenital anomalies, Matthew-Wood syndrome, MMEP syndrome, microphthalmia with brain and digit anomalies, syndromic microphthalmia type 5, microphthalmia-brain atrophy syndrome, oculoauricular syndrome, microphthalmia, syndromic 11, microphthalmia, syndromic 12, colobomatous microphthalmia-rhizomelic dysplasia syndrome, microphthalmia, Lenz type, Behrens Baumann dust syndrome, microphthalmia microtia fetal akinesia, RAB18 deficiency

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

517 retrieved; paginated sample, class counts are floors:

177 uncertain significance, 113 likely benign, 64 pathogenic, 56 benign, 49 conflicting classifications of pathogenicity, 31 benign/likely benign, 26 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070040	NM_001123385.2(BCOR):c.3090_3093del (p.Arg1031fs)	BCOR	Pathogenic	criteria provided, single submitter
1070616	NC_000023.10:g.(?39916388)(39937202_?)del	BCOR	Pathogenic	criteria provided, single submitter
1073665	NM_001123385.2(BCOR):c.4497C>A (p.Cys1499Ter)	BCOR	Pathogenic	criteria provided, single submitter
10911	NM_001123385.2(BCOR):c.254C>T (p.Pro85Leu)	BCOR	Pathogenic	criteria provided, single submitter
10912	NM_001123385.2(BCOR):c.4174-1G>T	BCOR	Pathogenic	no assertion criteria provided
10913	NM_001123385.2(BCOR):c.2926C>T (p.Arg976Ter)	BCOR	Pathogenic	criteria provided, multiple submitters, no conflicts
10914	NM_001123385.2(BCOR):c.3983del (p.Gln1328fs)	BCOR	Pathogenic	no assertion criteria provided
10917	NM_001123385.2(BCOR):c.3286del (p.Glu1096fs)	BCOR	Pathogenic	no assertion criteria provided
10918	NG_008880.1:g.(5324_84863)_?del	BCOR	Pathogenic	no assertion criteria provided
10919	NM_001123385.2(BCOR):c.2613del (p.Phe871fs)	BCOR	Pathogenic	no assertion criteria provided
1184476	NM_001123385.2(BCOR):c.4551del (p.Glu1518fs)	BCOR	Pathogenic	no assertion criteria provided
1299663	NM_001123385.2(BCOR):c.3226del (p.Glu1076fs)	BCOR	Pathogenic	no assertion criteria provided
1324437	NM_001123385.2(BCOR):c.2389_2390del (p.Val797fs)	BCOR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324440	NM_001123385.2(BCOR):c.2617C>T (p.Gln873Ter)	BCOR	Pathogenic	criteria provided, single submitter
1676781	NM_001123385.2(BCOR):c.1529dup (p.Val511fs)	BCOR	Pathogenic	criteria provided, single submitter
1679317	NM_001123385.2(BCOR):c.4328_4329del (p.Thr1443fs)	BCOR	Pathogenic	criteria provided, single submitter
1801366	NM_001123385.2(BCOR):c.558T>G (p.Tyr186Ter)	BCOR	Pathogenic	criteria provided, single submitter
180243	NC_000023.11:g.(?40051246)(40075180_?)del	BCOR	Pathogenic	no assertion criteria provided
180244	NM_001123385.2(BCOR):c.4742-141_4977-665del	BCOR	Pathogenic	no assertion criteria provided
180245	NM_001123385.2(BCOR):c.4304_4308del (p.Pro1435fs)	BCOR	Pathogenic	no assertion criteria provided
1805189	NM_001123385.2(BCOR):c.3165_3166delinsC (p.Lys1055fs)	BCOR	Pathogenic	criteria provided, single submitter
2109251	NM_001123385.2(BCOR):c.1233del (p.Lys412fs)	BCOR	Pathogenic	criteria provided, single submitter
2152340	NM_001123385.2(BCOR):c.3153G>A (p.Trp1051Ter)	BCOR	Pathogenic	criteria provided, single submitter
2426347	NC_000023.10:g.(?39921372)(39923872_?)del	BCOR	Pathogenic	criteria provided, single submitter
2574038	NM_001123385.2(BCOR):c.3355C>T (p.Gln1119Ter)	BCOR	Pathogenic	criteria provided, single submitter
2574149	NM_001123385.2(BCOR):c.3090_3091del (p.Glu1032fs)	BCOR	Pathogenic	criteria provided, single submitter
2584362	NM_001123385.2(BCOR):c.2983C>T (p.Gln995Ter)	BCOR	Pathogenic	criteria provided, single submitter
2737205	NM_001123385.2(BCOR):c.4140_4141del (p.Glu1382fs)	BCOR	Pathogenic	criteria provided, single submitter
2749835	NM_001123385.2(BCOR):c.3187_3188dup (p.Val1065fs)	BCOR	Pathogenic	criteria provided, single submitter
280600	NM_001123385.2(BCOR):c.4936dup (p.Leu1646fs)	BCOR	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
BCOR	Definitive	X-linked	microphthalmia, syndromic 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type

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
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCOR	BCL-6 corepressor	Transcriptional corepressor.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD

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
buccal mucosa cell	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCOR	2,188

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCOR	Q6W2J9	5

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
specification of axis polarity	1	16852.0×	6e-04	BCOR
negative regulation of tooth mineralization	1	8426.0×	6e-04	BCOR
negative regulation of bone mineralization	1	936.2×	0.004	BCOR
blastocyst hatching	1	543.6×	0.004	BCOR
odontogenesis	1	526.6×	0.004	BCOR
roof of mouth development	1	247.8×	0.007	BCOR
heart development	1	78.8×	0.017	BCOR
chromatin remodeling	1	73.0×	0.017	BCOR
negative regulation of DNA-templated transcription	1	31.6×	0.035	BCOR
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	BCOR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCOR	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
BCOR	2	Binding:2

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	BCOR

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)
BCOR	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.