Microphthalmia, syndromic 11

Summary

Microphthalmia, syndromic 11 (MONDO:0013734) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, syndromic 11
Mondo ID	MONDO:0013734
OMIM	614402
DOID	DOID:0111804
UMLS	C3553077
MedGen	765991
GARD	0024943
Is cancer (heuristic)	no

Also known as: MCOPS11 · microphthalmia, syndromic 11 · microphthalmia, syndromic type 11 · syndromic microphthalmia caused by mutation in VAX1 · VAX1 syndromic microphthalmia

Data availability: 39 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › microphthalmia, syndromic 11

Related subtypes (18): anophthalmia/microphthalmia-esophageal atresia syndrome, COFS syndrome, microphthalmia, syndromic 2, 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 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

39 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 14 likely benign, 3 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
36954	NM_001112704.2(VAX1):c.454C>A (p.Arg152Ser)	VAX1	Pathogenic	no assertion criteria provided
283191	NM_001112704.2(VAX1):c.642G>A (p.Leu214=)	VAX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3244903	NC_000010.10:g.(?117823909)(119750414_?)dup	CCDC172	Uncertain significance	criteria provided, single submitter
1360975	NM_001112704.2(VAX1):c.671_685dup (p.Gly224_Ala228dup)	VAX1	Uncertain significance	criteria provided, single submitter
1899584	NM_001112704.2(VAX1):c.821G>T (p.Ser274Ile)	VAX1	Uncertain significance	criteria provided, single submitter
196313	NM_001112704.2(VAX1):c.883A>G (p.Met295Val)	VAX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2038987	NM_001112704.2(VAX1):c.642G>C (p.Leu214Phe)	VAX1	Uncertain significance	criteria provided, single submitter
2169358	NM_001112704.2(VAX1):c.470A>G (p.Lys157Arg)	VAX1	Uncertain significance	criteria provided, single submitter
2502829	NM_001112704.2(VAX1):c.250G>A (p.Gly84Arg)	VAX1	Uncertain significance	no assertion criteria provided
2690437	NM_001112704.2(VAX1):c.853G>T (p.Ala285Ser)	VAX1	Uncertain significance	criteria provided, single submitter
2718283	NM_001112704.2(VAX1):c.80A>C (p.Lys27Thr)	VAX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2727679	NM_001112704.2(VAX1):c.638G>C (p.Ser213Thr)	VAX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3006218	NM_001112704.2(VAX1):c.541C>A (p.Leu181Met)	VAX1	Uncertain significance	criteria provided, single submitter
3188311	NM_001112704.2(VAX1):c.680C>T (p.Ala227Val)	VAX1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3628047	NM_001112704.2(VAX1):c.551dup (p.Arg186fs)	VAX1	Uncertain significance	criteria provided, single submitter
3637807	NM_001112704.2(VAX1):c.308C>T (p.Thr103Met)	VAX1	Uncertain significance	criteria provided, single submitter
3648715	NM_001112704.2(VAX1):c.49G>T (p.Glu17Ter)	VAX1	Uncertain significance	criteria provided, single submitter
3700024	NM_001112704.2(VAX1):c.548A>C (p.Glu183Ala)	VAX1	Uncertain significance	criteria provided, single submitter
4694922	NM_001112704.2(VAX1):c.210C>A (p.Asp70Glu)	VAX1	Uncertain significance	criteria provided, single submitter
473143	NM_001112704.2(VAX1):c.312dup (p.Thr105fs)	VAX1	Uncertain significance	criteria provided, single submitter
473144	NM_001112704.2(VAX1):c.993dup (p.Ala332fs)	VAX1	Uncertain significance	criteria provided, single submitter
1116533	NM_001112704.2(VAX1):c.624G>A (p.Ala208=)	VAX1	Likely benign	criteria provided, single submitter
1902601	NM_001112704.2(VAX1):c.375G>T (p.Val125=)	VAX1	Likely benign	criteria provided, single submitter
2026441	NM_001112704.2(VAX1):c.651G>C (p.Leu217=)	VAX1	Benign	criteria provided, single submitter
2092858	NM_001112704.2(VAX1):c.242-5C>T	VAX1	Likely benign	criteria provided, single submitter
2712305	NM_001112704.2(VAX1):c.241+19G>T	VAX1	Likely benign	criteria provided, single submitter
2743377	NM_001112704.2(VAX1):c.561G>A (p.Leu187=)	VAX1	Likely benign	criteria provided, single submitter
2780824	NM_001112704.2(VAX1):c.945C>T (p.Ala315=)	VAX1	Benign	criteria provided, single submitter
2852081	NM_001112704.2(VAX1):c.714C>T (p.Gly238=)	VAX1	Likely benign	criteria provided, single submitter
3650313	NM_001112704.2(VAX1):c.430-18C>G	VAX1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
VAX1	Limited	Autosomal recessive	microphthalmia, syndromic 11	4

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
VAX1	HGNC:12660	ENSG00000148704	Q5SQQ9	Ventral anterior homeobox 1	gencc,clinvar
CCDC172	HGNC:30524	ENSG00000182645	P0C7W6	Coiled-coil domain-containing protein 172	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VAX1	Ventral anterior homeobox 1	Transcription factor that may function in dorsoventral specification of the forebrain.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VAX1	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf
CCDC172	Other/Unknown	no		CCDC172

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
caudate nucleus	1
nucleus accumbens	1
primordial germ cell in gonad	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VAX1	38	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, caudate nucleus, nucleus accumbens
CCDC172	40	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VAX1	837
CCDC172	289

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCDC172	P0C7W6	88.63
VAX1	Q5SQQ9	65.77

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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neuroepithelial cell differentiation	1	1532.0×	0.005	VAX1
negative regulation of neuroblast proliferation	1	1203.7×	0.005	VAX1
astrocyte differentiation	1	766.0×	0.006	VAX1
neuroblast proliferation	1	366.4×	0.006	VAX1
camera-type eye development	1	358.6×	0.006	VAX1
skeletal muscle cell differentiation	1	343.9×	0.006	VAX1
roof of mouth development	1	247.8×	0.007	VAX1
neuron migration	1	133.8×	0.012	VAX1
central nervous system development	1	115.4×	0.013	VAX1
neuron differentiation	1	100.3×	0.013	VAX1
axon guidance	1	90.6×	0.013	VAX1
brain development	1	79.5×	0.014	VAX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	VAX1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
VAX1	0	0
CCDC172	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	VAX1, CCDC172

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)
VAX1	0	—
CCDC172	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.