Oculoauricular syndrome

Summary

Oculoauricular syndrome (MONDO:0012802) is a disease caused by HMX1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: HMX1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	oculoauricular syndrome
Mondo ID	MONDO:0012802
MeSH	C567416
OMIM	612109
Orphanet	157962
DOID	DOID:0060482
UMLS	C2677500
MedGen	393758
GARD	0016988
Is cancer (heuristic)	no

Also known as: OCACS · oculoauricular syndrome

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

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › oculoauricular syndrome

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, 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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14865	NM_018942.3(HMX1):c.215_240del (p.Leu72fs)	HMX1	Pathogenic	no assertion criteria provided
192315	NM_018942.3(HMX1):c.650A>C (p.Gln217Pro)	HMX1	Pathogenic	no assertion criteria provided
2432490	NM_018942.3(HMX1):c.3G>T (p.Met1Ile)	HMX1	Uncertain significance	criteria provided, single submitter
669515	NM_018942.3(HMX1):c.879A>G (p.Ala293=)	HMX1	Benign	criteria provided, multiple submitters, no conflicts

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
HMX1	Definitive	Autosomal recessive	oculoauricular syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HMX1	Orphanet:157962	Oculoauricular syndrome, Schorderet 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
HMX1	HGNC:5017	ENSG00000215612	Q9NP08	Homeobox protein HMX1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HMX1	Homeobox protein HMX1	DNA-binding protein that binds to the 5’-CAAG-3’ core sequence.

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)
HMX1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HMX1	43	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, amygdala

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HMX1	217

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HMX1	Q9NP08	63.45

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
negative regulation of DNA-templated transcription	1	31.6×	0.063	HMX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HMX1

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
HMX1	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	HMX1

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)
HMX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.