Microphthalmia, syndromic 1

Summary

Microphthalmia, syndromic 1 (MONDO:0010671) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 22
• Phenotypes (HPO): 4

Clinical features

Signs & symptoms

Clinical features (HPO)

4 HPO clinical features (Orphanet curated; top 4 by frequency):

HPO ID	Term	Frequency
HP:0000528	Anophthalmia	Very frequent (80-99%)
HP:0000568	Microphthalmia	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0009755	Ankyloblepharon	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, syndromic 1
Mondo ID	MONDO:0010671
MeSH	C537464, C564457
OMIM	309800
Orphanet	85275
DOID	DOID:0111799
SNOMED CT	438504004, 717222003
UMLS	C0796016
MedGen	162898
GARD	0015304
Is cancer (heuristic)	no

Also known as: ANOP1, formerly · Lenz dysplasia · Lenz microphthalmia syndrome · MAA, formerly · MCOPS1 · MCOPS4 · MCOPS4, formerly · microphthalmia syndromic 4 · microphthalmia with ankyloblepharon and intellectual disability · microphthalmia with ankyloblepharon and mental retardation · microphthalmia, syndromic 1 · microphthalmia, syndromic 4, formerly · microphthalmia, syndromic type 1 · syndromic microphthalmia type 4

Data availability: 22 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › microphthalmia, syndromic 1

Related subtypes (18): anophthalmia/microphthalmia-esophageal atresia syndrome, COFS syndrome, microphthalmia, syndromic 2, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, 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

22 retrieved; paginated sample, class counts are floors:

5 conflicting classifications of pathogenicity, 5 uncertain significance, 5 benign/likely benign, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
102423	NM_003491.4(NAA10):c.471+2T>A	NAA10	Pathogenic	no assertion criteria provided
29927	NM_003491.4(NAA10):c.109T>C (p.Ser37Pro)	NAA10	Pathogenic	criteria provided, multiple submitters, no conflicts
617462	NM_003491.4(NAA10):c.*39A>G	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
916544	NM_003491.4(NAA10):c.47A>C (p.His16Pro)	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973227	NM_003491.4(NAA10):c.257T>G (p.Leu86Arg)	NAA10	Pathogenic	criteria provided, single submitter
617463	NM_003491.4(NAA10):c.*43A>G	NAA10	Likely pathogenic	criteria provided, single submitter
210518	NM_001123385.2(BCOR):c.2035G>A (p.Val679Ile)	BCOR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300158	NM_003491.4(NAA10):c.16G>C (p.Ala6Pro)	LOC130068840	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065122	NM_003491.4(NAA10):c.455_458del (p.Thr152fs)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
373777	NM_003491.4(NAA10):c.440T>C (p.Met147Thr)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
617458	NM_003491.4(NAA10):c.*40A>G	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337408	NM_001123385.2(BCOR):c.1078C>T (p.His360Tyr)	BCOR	Uncertain significance	criteria provided, multiple submitters, no conflicts
95768	NM_001123385.2(BCOR):c.2125G>A (p.Gly709Ser)	BCOR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1401268	NM_003491.4(NAA10):c.563C>T (p.Pro188Leu)	NAA10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679677	NM_003491.4(NAA10):c.418G>T (p.Asp140Tyr)	NAA10	Uncertain significance	criteria provided, single submitter
3383025	NM_003491.4(NAA10):c.244C>T (p.Arg82Trp)	NAA10	Uncertain significance	criteria provided, single submitter
434506	NM_001123385.2(BCOR):c.4680G>A (p.Thr1560=)	BCOR	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
591128	NM_001123385.2(BCOR):c.2423_2424delinsAC (p.Leu808His)	BCOR	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
760314	NM_001123385.2(BCOR):c.2423T>A (p.Leu808His)	BCOR	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
133688	NM_001123385.2(BCOR):c.409G>A (p.Val137Ile)	LOC126863239	Likely benign	criteria provided, multiple submitters, no conflicts
696167	NM_001123385.2(BCOR):c.482C>T (p.Ala161Val)	LOC126863239	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1648582	NM_003491.4(NAA10):c.179+20G>A	NAA10	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 6 · 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
NAA10	Moderate	X-linked	microphthalmia, syndromic 1	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NAA10	Orphanet:276432	Ogden syndrome
NAA10	Orphanet:568	Microphthalmia, Lenz type
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NAA10	HGNC:18704	ENSG00000102030	P41227	N-alpha-acetyltransferase 10	gencc,clinvar
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NAA10	N-alpha-acetyltransferase 10	Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity.
BCOR	BCL-6 corepressor	Transcriptional corepressor.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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	8.6×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NAA10	Enzyme (other)	yes	2.3.1.255	GNAT_dom, Acyl_CoA_acyltransferase, Ard1-like
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD

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
apex of heart	1
lower esophagus muscularis layer	1
right hemisphere of cerebellum	1
buccal mucosa cell	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NAA10	288	ubiquitous	marker	right hemisphere of cerebellum, apex of heart, lower esophagus muscularis layer
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NAA10	2,579
BCOR	2,188

Intra-cohort edges

A	B	Sources
BCOR	NAA10	biogrid_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NAA10	P41227	12
BCOR	Q6W2J9	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 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	8426.0×	5e-04	BCOR
positive regulation of protein refolding	1	8426.0×	5e-04	NAA10
negative regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1	8426.0×	5e-04	NAA10
negative regulation of tooth mineralization	1	4213.0×	8e-04	BCOR
negative regulation of bone mineralization	1	468.1×	0.006	BCOR
blastocyst hatching	1	271.8×	0.007	BCOR
odontogenesis	1	263.3×	0.007	BCOR
roof of mouth development	1	123.9×	0.013	BCOR
protein maturation	1	81.8×	0.018	NAA10
heart development	1	39.4×	0.032	BCOR
chromatin remodeling	1	36.5×	0.032	BCOR
negative regulation of DNA-templated transcription	1	15.8×	0.068	BCOR
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	BCOR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
NAA10	0	0
BCOR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NAA10	2	Binding:2
BCOR	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NAA10	2.3.1.255, 2.3.1.258, 2.3.1.48	N-terminal amino-acid Nalpha-acetyltransferase NatA, N-terminal methionine Nalpha-acetyltransferase NatE, histone acetyltransferase

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

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	1	NAA10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BCOR

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NAA10	2	—
BCOR	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.