Esotropia

Summary

Esotropia (MONDO:0004896) is a disease with 3 cohort genes and 20 clinical trials. Top therapeutic interventions include botulinum toxin type a, cyclopentolate, and sodium chloride.

At a glance

• Cohort genes: 3
• ClinVar variants: 6
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	esotropia
Mondo ID	MONDO:0004896
MeSH	D004948
DOID	DOID:9840
ICD-10-CM	H50.0
ICD-11	459766644
NCIT	C34596
SNOMED CT	16596007
UMLS	C0014877
MedGen	4550
Is cancer (heuristic)	no

Also known as: internal strabismus

Data availability: 6 ClinVar variants.

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 › strabismus › esotropia

Related subtypes (10): paralytic strabismus, exotropia, conjugate gaze palsy, intermittent squint, internuclear ophthalmoplegia, mechanical strabismus, hypertropia, cyclotropia, hypotropia, monofixation syndrome

Subtypes (3): monocular esotropia, accommodative esotropia, alternating esotropia

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
242882	NM_013275.6(ANKRD11):c.5317G>T (p.Glu1773Ter)	ANKRD11	Pathogenic	no assertion criteria provided
523459	NM_001372066.1(TFAP2A):c.1043_1044del (p.Lys348fs)	TFAP2A	Pathogenic	criteria provided, multiple submitters, no conflicts
267799	46;XY;t(3;17)(p14.3;q24.3)dn		Likely pathogenic	criteria provided, single submitter
267808	46;XY;t(4;14)(p15.32;q32.1)dn		Uncertain significance	criteria provided, single submitter
267862	46;XY;t(1;3)(p22;q21)dn		Uncertain significance	criteria provided, single submitter
2570688	NM_004104.5(FASN):c.1249_1250dup (p.Ala418fs)	FASN	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2A	Orphanet:1297	Branchio-oculo-facial syndrome
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFAP2A	HGNC:11742	ENSG00000137203	P05549	Transcription factor AP-2-alpha	clinvar
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
FASN	HGNC:3594	ENSG00000169710	P49327	Fatty acid synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2A	Transcription factor AP-2-alpha	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
FASN	Fatty acid synthase	Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.33

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	5.8×	0.321
Enzyme (other)	1	4.0×	0.321
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2A	Transcription factor	no		TF_AP2, TF_AP2_alpha_N, TF_AP2_C
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
FASN	Enzyme (other)	yes	2.3.1.39	Thioesterase, Ac_transferase_dom_sf, Ppantetheine_attach_site

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
upper leg skin	1
stromal cell of endometrium	1
sural nerve	1
tendon of biceps brachii	1
endometrium epithelium	1
right hemisphere of cerebellum	1
skin of abdomen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2A	220	ubiquitous	marker	upper leg skin, gingival epithelium, gingiva
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
FASN	273	ubiquitous	marker	right hemisphere of cerebellum, endometrium epithelium, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FASN	6,551
TFAP2A	2,734
ANKRD11	2,384

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FASN	P49327	34
TFAP2A	P05549	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKRD11	Q6UB99	39.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 3 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
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	1427.5×	0.006	TFAP2A
TFAP2 (AP-2) family regulates transcription of cell cycle factors	1	1142.0×	0.006	TFAP2A
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation	1	1142.0×	0.006	TFAP2A
ChREBP activates metabolic gene expression	1	634.4×	0.006	FASN
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	571.0×	0.006	TFAP2A
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis	1	571.0×	0.006	FASN
Activation of the TFAP2 (AP-2) family of transcription factors	1	475.8×	0.006	TFAP2A
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.006	TFAP2A
Vitamin B5 (pantothenate) metabolism	1	380.7×	0.006	FASN
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	380.7×	0.006	TFAP2A
Developmental Lineage of Mammary Stem Cells	1	380.7×	0.006	TFAP2A
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	317.2×	0.006	TFAP2A
Specification of the neural plate border	1	317.2×	0.006	TFAP2A
SUMOylation of transcription factors	1	285.5×	0.006	TFAP2A
Fatty acyl-CoA biosynthesis	1	219.6×	0.008	FASN
Dengue Virus Genome Translation and Replication	1	158.6×	0.010	FASN
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.011	TFAP2A
Activation of gene expression by SREBF (SREBP)	1	129.8×	0.011	FASN
Gastrulation	1	129.8×	0.011	TFAP2A
MITF-M-dependent gene expression	1	90.6×	0.014	TFAP2A
MITF-M-regulated melanocyte development	1	57.1×	0.022	TFAP2A
Dengue Virus-Host Interactions	1	22.8×	0.051	FASN
RNA Polymerase II Transcription	1	11.3×	0.098	TFAP2A
Gene expression (Transcription)	1	8.9×	0.118	TFAP2A
Generic Transcription Pathway	1	7.5×	0.133	TFAP2A
Developmental Biology	1	7.2×	0.134	TFAP2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
optic cup structural organization	1	5617.3×	0.006	TFAP2A
optic vesicle morphogenesis	1	2808.7×	0.006	TFAP2A
oculomotor nerve formation	1	2808.7×	0.006	TFAP2A
positive regulation of tooth mineralization	1	1872.4×	0.006	TFAP2A
acetyl-CoA metabolic process	1	802.5×	0.007	FASN
trigeminal nerve development	1	802.5×	0.007	TFAP2A
cellular response to iron ion	1	802.5×	0.007	TFAP2A
ether lipid biosynthetic process	1	624.1×	0.007	FASN
neutrophil differentiation	1	624.1×	0.007	FASN
host-mediated perturbation of viral process	1	624.1×	0.007	FASN
fatty-acyl-CoA biosynthetic process	1	624.1×	0.007	FASN
response to caloric restriction	1	510.7×	0.008	FASN
establishment of endothelial intestinal barrier	1	468.1×	0.008	FASN
obsolete negative regulation of transcription by competitive promoter binding	1	432.1×	0.008	TFAP2A
eyelid development in camera-type eye	1	351.1×	0.009	TFAP2A
negative regulation of reactive oxygen species metabolic process	1	312.1×	0.010	TFAP2A
monocyte differentiation	1	267.5×	0.011	FASN
retina layer formation	1	216.1×	0.011	TFAP2A
mammary gland development	1	216.1×	0.011	FASN
cellular response to interleukin-4	1	216.1×	0.011	FASN
bone morphogenesis	1	200.6×	0.011	TFAP2A
embryonic cranial skeleton morphogenesis	1	193.7×	0.011	TFAP2A
embryonic forelimb morphogenesis	1	165.2×	0.012	TFAP2A
skeletal system morphogenesis	1	165.2×	0.012	ANKRD11
face morphogenesis	1	165.2×	0.012	ANKRD11
regulation of cell differentiation	1	144.0×	0.013	TFAP2A
positive regulation of bone mineralization	1	130.6×	0.014	TFAP2A
fatty acid biosynthetic process	1	117.0×	0.015	FASN
inner ear morphogenesis	1	100.3×	0.016	TFAP2A
odontogenesis of dentin-containing tooth	1	100.3×	0.016	ANKRD11

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Onabotulinumtoxina	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
FASN	RABEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FASN	8	4
TFAP2A	0	0
ANKRD11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RABEPRAZOLE	4	FASN
PANTOPRAZOLE	4	FASN
OMEPRAZOLE	4	FASN
ORLISTAT	4	FASN
LANSOPRAZOLE	4	FASN
EPIGALOCATECHIN GALLATE	3	FASN
LUTEOLIN	2	FASN
DENIFANSTAT	2	FASN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FASN	142	Binding:136, Functional:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FASN	2.3.1.39, 2.3.1.85	[acyl-carrier-protein] S-malonyltransferase, fatty-acid synthase system

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
FASN	142

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

8 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)
RABEPRAZOLE	4	FASN
PANTOPRAZOLE	4	FASN
OMEPRAZOLE	4	FASN
ORLISTAT	4	FASN
LANSOPRAZOLE	4	FASN
EPIGALOCATECHIN GALLATE	3	FASN
LUTEOLIN	2	FASN
DENIFANSTAT	2	FASN

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FASN
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	TFAP2A, ANKRD11

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)
TFAP2A	0	—
ANKRD11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE3	4
PHASE4	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01460355	PHASE4	COMPLETED	Comparison of Two Treatments for Strabismus Correction: Botulinum Toxin A Associated to Surgery and Surgery Alone
NCT06077682	PHASE4	UNKNOWN	Cycloplegic Refraction in Pediatric Patients With Esotropia
NCT07470164	PHASE3	NOT_YET_RECRUITING	A Randomized Trial of Botulinum Toxin A vs Strabismus Surgery for Esotropia >10 to ≤30PD
NCT00000121	PHASE3	COMPLETED	The Prism Adaptation Study (PAS)
NCT01616108	PHASE2/PHASE3	UNKNOWN	Bupivacaine Injection of Eye Muscles to Treat Strabismus
NCT03459092	PHASE3	COMPLETED	Botox Instead of Strabismus Surgery (BISS)
NCT05527015	PHASE3	WITHDRAWN	Bifocal Spectacles vs. Single Vision Spectacles for Esotropia Greater at Near
NCT06614335	Not specified	ACTIVE_NOT_RECRUITING	An Observational Cohort Study to Explore the Clinical Outcome of Congenital Strabismmus Based on Etiology and Timing of Surgery
NCT06622044	Not specified	RECRUITING	Vision Therapy Versus Prism Treatment in Small-angle Acute Acquired Concomitant Esotropia
NCT06714877	Not specified	NOT_YET_RECRUITING	Botulinum Toxin Injection Versus Prism Treatment in Small-angle Acute Acquired Concomitant Esotropia
NCT06714890	Not specified	NOT_YET_RECRUITING	Accommodation-Related Visual Training Combined with Transcranial Electrical Stimulation Versus Visual Training Alone for the Treatment of Accommodation Dysfunction
NCT07446621	Not specified	NOT_YET_RECRUITING	Risk Factors And Surgical Outcomes Of Strabismus Reoperation
NCT00000163	Not specified	COMPLETED	Congenital Esotropia Observational Study (CEOS)
NCT00746304	Not specified	COMPLETED	Long-Term Outcomes in the Treatment of Infantile and Acquired Esotropia With Botulinum Toxin
NCT00993174	Not specified	UNKNOWN	Surgery for Esotropia Under Topical Anesthesia
NCT01166503	Not specified	COMPLETED	Early Versus Delayed Surgery for Infantile Esotropia
NCT02404324	Not specified	UNKNOWN	Conservative Treatment of Esotropia in Children up to 3 Years Old
NCT02570555	Not specified	COMPLETED	Strabismus Surgery and Driving Ability
NCT04429659	Not specified	COMPLETED	Changes in Refractive Error in Patients With Both Partially Refractive Esotropia and Amblyopia
NCT05615519	Not specified	UNKNOWN	Validation of a Smartphone-based Intelligent Diagnosis and Measurement for Strabismus

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOTULINUM TOXIN TYPE A	4	1
CYCLOPENTOLATE	4	1
SODIUM CHLORIDE	4	1
TROPICAMIDE	4	1
CHEMBL1457550	0	1