Ophthalmoplegia

Summary

Ophthalmoplegia (MONDO:0003425) is a disease with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include nicotinamide riboside.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ophthalmoplegia
Mondo ID	MONDO:0003425
MeSH	D009886
DOID	DOID:539
ICD-11	1848588735
SNOMED CT	78097002
UMLS	C0029089
MedGen	45205
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (5): strabismus, pathologic nystagmus, congenital fibrosis of extraocular muscles, Tolosa-Hunt syndrome, Weber syndrome

Subtypes (3): exophthalmic ophthalmoplegia, internuclear ophthalmoplegia, progressive external ophthalmoplegia

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
986389	NM_004521.3(KIF5B):c.762CAA[1] (p.Asn255del)	KIF5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
KIF5B	HGNC:6324	ENSG00000170759	P33176	Kinesin-1 heavy chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF5B	Kinesin-1 heavy chain	Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF5B	Enzyme (other)	yes	5.6.1.3	Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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
caput epididymis	1
cauda epididymis	1
cranial nerve II	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF5B	303	ubiquitous	marker	cauda epididymis, caput epididymis, cranial nerve II

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF5B	3,606

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF5B	P33176	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHO GTPases activate KTN1	1	1038.2×	0.021	KIF5B
Insulin processing	1	456.8×	0.021	KIF5B
Peptide hormone metabolism	1	271.9×	0.021	KIF5B
Signaling by ALK in cancer	1	271.9×	0.021	KIF5B
Kinesins	1	178.4×	0.024	KIF5B
Signaling by ALK fusions and activated point mutants	1	150.3×	0.024	KIF5B
Golgi-to-ER retrograde transport	1	132.8×	0.024	KIF5B
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.024	KIF5B
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.024	KIF5B
MHC class II antigen presentation	1	89.2×	0.026	KIF5B
RHO GTPase Effectors	1	68.0×	0.029	KIF5B
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.029	KIF5B
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.031	KIF5B
Membrane Trafficking	1	37.1×	0.038	KIF5B
Hemostasis	1	36.0×	0.038	KIF5B
Vesicle-mediated transport	1	34.8×	0.038	KIF5B
Signaling by Rho GTPases	1	34.2×	0.038	KIF5B
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	KIF5B
Adaptive Immune System	1	29.8×	0.041	KIF5B
Disease	1	13.1×	0.084	KIF5B
Immune System	1	13.0×	0.084	KIF5B
Metabolism of proteins	1	12.4×	0.084	KIF5B
Signal Transduction	1	10.2×	0.098	KIF5B

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
regulation of modification of synapse structure, modulating synaptic transmission	1	8426.0×	0.001	KIF5B
anterograde neuronal dense core vesicle transport	1	4213.0×	0.001	KIF5B
retrograde neuronal dense core vesicle transport	1	3370.4×	0.001	KIF5B
cytoplasm organization	1	2808.7×	0.001	KIF5B
plus-end-directed vesicle transport along microtubule	1	2808.7×	0.001	KIF5B
mitocytosis	1	2808.7×	0.001	KIF5B
stress granule disassembly	1	2407.4×	0.001	KIF5B
anterograde dendritic transport of neurotransmitter receptor complex	1	2407.4×	0.001	KIF5B
positive regulation of potassium ion transport	1	2106.5×	0.001	KIF5B
anterograde axonal protein transport	1	2106.5×	0.001	KIF5B
mitochondrion transport along microtubule	1	1404.3×	0.001	KIF5B
positive regulation of synaptic transmission, GABAergic	1	991.3×	0.002	KIF5B
vesicle transport along microtubule	1	887.0×	0.002	KIF5B
centrosome localization	1	887.0×	0.002	KIF5B
synaptic vesicle transport	1	842.6×	0.002	KIF5B
lysosome localization	1	526.6×	0.003	KIF5B
natural killer cell mediated cytotoxicity	1	432.1×	0.003	KIF5B
microtubule-based movement	1	295.6×	0.004	KIF5B
positive regulation of protein localization to plasma membrane	1	271.8×	0.004	KIF5B
regulation of membrane potential	1	230.8×	0.005	KIF5B
cellular response to type II interferon	1	208.1×	0.005	KIF5B
axon guidance	1	90.6×	0.011	KIF5B

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KIF5B	LENVATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIF5B	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LENVATINIB	4	KIF5B
CABOZANTINIB	4	KIF5B
VANDETANIB	4	KIF5B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KIF5B	43	Binding:37, Functional:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF5B	5.6.1.3	plus-end-directed kinesin ATPase

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
LENVATINIB	4	KIF5B
CABOZANTINIB	4	KIF5B
VANDETANIB	4	KIF5B

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KIF5B
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03135574	Not specified	COMPLETED	Prevalence of a High-intensity Signal of the Oculomotor Nerve on T2 MRI Sequence in Patients With Ophthalmoplegia
NCT03269682	Not specified	COMPLETED	Prevalence of Contrast Enhancement of the Oculomotor Nerve on 3D PD T1 MRI Sequence in Patients With Ophthalmoplegia
NCT03432871	Not specified	COMPLETED	Nicotinamide Riboside and Mitochondrial Biogenesis
NCT04436198	Not specified	TERMINATED	Capsular Tension Rings in Intraocular Lens Rotation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NICOTINAMIDE RIBOSIDE	3	1
CHEMBL5649155	0	1