Ocular motility disease

Summary

Ocular motility disease (MONDO:0001584) is a disease (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ocular motility disease
Mondo ID	MONDO:0001584
EFO	EFO:1001990
DOID	DOID:1279
SNOMED CT	45030009
UMLS	C0028850
MedGen	14457
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › cranial nerve neuropathy › ocular motility disease

Related subtypes (16): vestibulocochlear nerve disorder, hypoglossal nerve disorder, facial nerve disorder, optic nerve disorder, cranial nerve neoplasm, accessory nerve disorder, glossopharyngeal nerve disorder, olfactory nerve disorder, cranial nerve palsy, trigeminal nerve disorder, third cranial nerve disorder, pseudobulbar palsy, trochlear nerve disorder, jaw-winking syndrome, cranial neuralgia, abducens nerve disorder

Subtypes (6): ophthalmoplegia, strabismus, pathologic nystagmus, congenital fibrosis of extraocular muscles, Tolosa-Hunt syndrome, Weber syndrome

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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
340223	NM_001379500.1(COL18A1):c.1507G>A (p.Gly503Ser)	COL18A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4070913	NM_001379500.1(COL18A1):c.1358C>T (p.Pro453Leu)	COL18A1	Uncertain significance	criteria provided, single submitter
3024414	NM_175737.4(KLB):c.1469G>A (p.Arg490Gln)	KLB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL18A1	Orphanet:1571	Knobloch syndrome

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
KLB	HGNC:15527	ENSG00000134962	Q86Z14	Beta-klotho	clinvar
COL18A1	HGNC:2195	ENSG00000182871	P39060	Collagen alpha-1(XVIII) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLB	Beta-klotho	Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis.
COL18A1	Collagen alpha-1(XVIII) chain	Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLB	Other/Unknown	no		Glyco_hydro_1, GH_hydrolase_sf
COL18A1	Other/Unknown	no		Collagen, DUF959_COL18_N, Collagenase_NC10/endostatin

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
buccal mucosa cell	1
liver	1
sperm	1
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLB	146	broad	marker	sperm, buccal mucosa cell, liver
COL18A1	266	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL18A1	2,316
KLB	1,139

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL18A1	P39060	9
KLB	Q86Z14	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
betaKlotho-mediated ligand binding	1	1903.3×	0.010	KLB
Downstream signaling of activated FGFR4	1	1903.3×	0.010	KLB
IGF1R signaling cascade	1	713.8×	0.010	KLB
IRS-mediated signalling	1	519.1×	0.010	KLB
IRS-related events triggered by IGF1R	1	519.1×	0.010	KLB
Signaling by FGFR4	1	519.1×	0.010	KLB
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1	475.8×	0.010	KLB
Signaling by Insulin receptor	1	439.2×	0.010	KLB
FGFR4 ligand binding and activation	1	407.9×	0.010	KLB
Phospholipase C-mediated cascade; FGFR4	1	380.7×	0.010	KLB
Insulin receptor signalling cascade	1	335.9×	0.010	KLB
PI-3K cascade:FGFR4	1	285.5×	0.010	KLB
SHC-mediated cascade:FGFR4	1	271.9×	0.010	KLB
FRS-mediated FGFR4 signaling	1	248.3×	0.011	KLB
Negative regulation of FGFR4 signaling	1	203.9×	0.012	KLB
Laminin interactions	1	190.3×	0.012	COL18A1
PI3K/AKT Signaling in Cancer	1	184.2×	0.012	KLB
Signaling by FGFR	1	173.0×	0.012	KLB
Activation of Matrix Metalloproteinases	1	154.3×	0.013	COL18A1
Negative regulation of the PI3K/AKT network	1	139.3×	0.013	KLB
PI3K Cascade	1	135.9×	0.013	KLB
Collagen chain trimerization	1	129.8×	0.013	COL18A1
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.016	COL18A1
Collagen degradation	1	87.8×	0.017	COL18A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.017	COL18A1
Integrin cell surface interactions	1	67.2×	0.021	COL18A1
MAPK1/MAPK3 signaling	1	65.6×	0.021	KLB
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.021	KLB
MAPK family signaling cascades	1	51.4×	0.025	KLB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.025	KLB

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
response to hydrostatic pressure	1	2106.5×	0.004	COL18A1
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	1404.3×	0.004	KLB
endothelial cell morphogenesis	1	526.6×	0.008	COL18A1
animal organ morphogenesis	1	95.8×	0.031	COL18A1
carbohydrate metabolic process	1	68.0×	0.032	KLB
skeletal system development	1	62.9×	0.032	COL18A1
visual perception	1	39.8×	0.042	COL18A1
response to xenobiotic stimulus	1	34.5×	0.042	COL18A1
angiogenesis	1	31.2×	0.042	COL18A1
negative regulation of cell population proliferation	1	21.1×	0.056	COL18A1
cell adhesion	1	18.7×	0.057	COL18A1
positive regulation of cell population proliferation	1	16.8×	0.059	KLB

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
KLB	0	0
COL18A1	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	KLB, COL18A1

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)
KLB	0	—
COL18A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.