Fibrosis of extraocular muscles, congenital, 3b

Summary

Fibrosis of extraocular muscles, congenital, 3b (MONDO:0800209) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibrosis of extraocular muscles, congenital, 3b
Mondo ID	MONDO:0800209
UMLS	C2751105
MedGen	416468
GARD	0026483
Is cancer (heuristic)	no

Also known as: CFEOM3B

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › cranial nerve neuropathy › ocular motility disease › congenital fibrosis of extraocular muscles › fibrosis of extraocular muscles, congenital, 3b

Related subtypes (7): fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement, fibrosis of extraocular muscles, congenital, 2, fibrosis of extraocular muscles, congenital, 3c, Tukel syndrome, fibrosis of extraocular muscles, congenital, with synergistic divergence, fibrosis of extraocular muscles, congenital, 5, congenital fibrosis of extraocular muscles type 1

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:

3 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2436	NM_001173464.2(KIF21A):c.2860C>T (p.Arg954Trp)	KIF21A	Pathogenic	criteria provided, multiple submitters, no conflicts
2437	NM_001173464.2(KIF21A):c.2861G>A (p.Arg954Gln)	KIF21A	Pathogenic	criteria provided, multiple submitters, no conflicts
2442	NM_001173464.2(KIF21A):c.2841G>A (p.Met947Ile)	KIF21A	Pathogenic	no assertion criteria provided
806865	NM_001173464.2(KIF21A):c.2516C>T (p.Pro839Leu)	KIF21A	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
KIF21A	Definitive	Autosomal dominant	congenital fibrosis of extraocular muscles	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIF21A	Orphanet:45358	Congenital fibrosis of extraocular muscles
KIF21A	Orphanet:994	Fetal akinesia deformation sequence

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
KIF21A	HGNC:19349	ENSG00000139116	Q7Z4S6	Kinesin-like protein KIF21A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF21A	Kinesin-like protein KIF21A	Processive microtubule plus-end directed motor protein involved in neuronal axon guidance.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIF21A	Scaffold/PPI	no		WD40_rpt, Kinesin_motor_dom, WD40/YVTN_repeat-like_dom_sf

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
dorsal root ganglion	1
pons	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF21A	253	ubiquitous	marker	dorsal root ganglion, substantia nigra pars compacta, pons

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF21A	1,564

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF21A	Q7Z4S6	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Kinesins	1	178.4×	0.019	KIF21A
Golgi-to-ER retrograde transport	1	132.8×	0.019	KIF21A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.019	KIF21A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.019	KIF21A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.024	KIF21A
Membrane Trafficking	1	37.1×	0.029	KIF21A
Hemostasis	1	36.0×	0.029	KIF21A
Vesicle-mediated transport	1	34.8×	0.029	KIF21A

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 microtubule depolymerization	1	4213.0×	0.001	KIF21A
regulation of axon guidance	1	2407.4×	0.001	KIF21A
cortical microtubule organization	1	1872.4×	0.001	KIF21A
regulation of microtubule polymerization	1	1123.5×	0.001	KIF21A
anterograde axonal transport	1	581.1×	0.002	KIF21A
microtubule-based movement	1	295.6×	0.003	KIF21A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
KIF21A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KIF21A	4	Binding:3, Toxicity:1

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	KIF21A

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)
KIF21A	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.