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MCID: OCL011
MIFTS: 46

Ocular Motility Disease

Categories: Eye diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Drugs
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Aliases & Classifications for Ocular Motility Disease

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MalaCards integrated aliases for Ocular Motility Disease:

Name: Ocular Motility Disease 12 15 17
Ocular Motility Disorders 77 54 74
Abnormality of Eye Movement 30 6
Motor Neuro-Ophthalmic Disorders 54
Disorder of Eye Movements 12
Eye Movement Disorders 44
Eye Movement Disorder 12

Classifications:

MalaCards categories:
Global: Rare diseases
Anatomical: Eye diseases Neuronal diseases
See all MalaCards categories (disease lists)


External Ids:

Disease Ontology 12 DOID:1279
ICD9CM 36 378.9
MeSH 45 D015835
SNOMED-CT 69 45030009
UMLS 74 C0028850
Sources

Summaries for Ocular Motility Disease

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MedlinePlus : 44 When you look at an object, you're using several muscles to move both eyes to focus on it. If you have a problem with the muscles, the eyes don't work properly. There are many kinds of eye movement disorders. Two common ones are Strabismus - a disorder in which the two eyes don't line up in the same direction. This results in "crossed eyes" or "walleye." Nystagmus - fast, uncontrollable movements of the eyes, sometimes called "dancing eyes" Some eye movement disorders are present at birth. Others develop over time and may be associated with other problems, such as injuries. Treatments include glasses, patches, eye muscle exercises, and surgery. There is no cure for some kinds of eye movement disorders, such as most kinds of nystagmus.

MalaCards based summary : Ocular Motility Disease, also known as ocular motility disorders, is related to fibrosis of extraocular muscles, congenital, 2 and strabismus, and has symptoms including ophthalmoplegia, eye manifestations and hyperexplexia. An important gene associated with Ocular Motility Disease is KIF21A (Kinesin Family Member 21A). The drugs Dopamine and Povidone have been mentioned in the context of this disorder. Affiliated tissues include eye, brain and testes, and related phenotype is cellular.

Wikipedia : 77 Eye movement includes the voluntary or involuntary movement of the eyes, helping in acquiring, fixating... more...

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Related Diseases for Ocular Motility Disease

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Diseases related to Ocular Motility Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 93)
# Related Disease Score Top Affiliating Genes
1 fibrosis of extraocular muscles, congenital, 2 32.2 KIF21A PHOX2A
2 strabismus 29.9 CHN1 FRMD7 GPR143 KIF21A PHOX2A VANGL2
3 brown's tendon sheath syndrome 11.8
4 motor neuro-ophthalmic disorders 11.8
5 fibrosis of extraocular muscles, congenital, 1 11.2
6 fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement 11.1
7 fibrosis of extraocular muscles, congenital, 5 11.1
8 duane retraction syndrome 1 10.8
9 duane syndrome type 2 10.8
10 isolated duane retraction syndrome 10.8
11 gaucher disease, type i 10.8
12 wildervanck syndrome 10.8
13 duane retraction syndrome 2 10.8
14 duane retraction syndrome 3 with or without deafness 10.8
15 duane syndrome type 1 10.8
16 movement disease 10.7
17 x-linked infantile nystagmus 10.4 FRMD7 GPR143
18 mitochondrial neurogastrointestinal encephalopathy disease 10.4 POLG TYMP
19 enophthalmos 10.4 CHN1 TNNI3K
20 ataxia neuropathy spectrum 10.4 POLG TWNK
21 mitochondrial neurogastrointestinal encephalomyopathy 10.3 POLG TYMP
22 duane retraction syndrome 10.3 CHN1 KIF21A TNNI3K
23 dissociated nystagmus 10.3 FRMD7 KANTR
24 alternating esotropia 10.3 CHN1 KANTR
25 mitochondrial dna depletion syndrome 4a 10.2 POLG TWNK TYMP
26 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 10.2 POLG TWNK
27 3-methylglutaconic aciduria, type v 10.2 POLG TWNK TYMP
28 accommodative esotropia 10.2 CHN1 KANTR
29 exotropia 10.2 CHN1 KIF21A PHOX2A TNNI3K
30 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 10.2 POLG TWNK TYMP
31 myopathy, proximal, and ophthalmoplegia 10.2 MYH2 RYR1
32 3-methylglutaconic aciduria, type iv 10.2 POLG RYR1
33 oculomotor nerve paralysis 10.2 CHN1 KANTR
34 third cranial nerve disease 10.2 CHN1 KANTR
35 charcot-marie-tooth disease, dominant intermediate b 10.2 MTM1 RYR1
36 mitochondrial dna depletion syndrome 1 10.2 POLG TYMP
37 facial nerve disease 10.2 KANTR KIF21A PHOX2A
38 hypertropia 10.2 CHN1 KANTR KIF21A
39 congenital ptosis 10.1 CHN1 KIF21A RYR1 TNNI3K
40 central core myopathy 10.1 MTM1 RYR1
41 orbital disease 10.1 CHN1 RHNO1 TNNI3K
42 intracranial sinus thrombosis 10.1 NT5C3A RHNO1
43 cavernous sinus thrombosis 10.1 NT5C3A RHNO1
44 tukel syndrome 10.1 CHN1 KIF21A PHOX2A ROBO3 TNNI3K
45 petroclival meningioma 10.1 KANTR NT5C3A
46 multiple sclerosis 10.1
47 paralytic squint 10.0 CHN1 KANTR KIF21A PHOX2A
48 cranial nerve palsy 10.0 CHN1 NT5C3A RHNO1
49 mitochondrial dna depletion syndrome 7 10.0 SLC25A4 TWNK
50 congenital nystagmus 10.0 FRMD7 GPR143

Comorbidity relations with Ocular Motility Disease via Phenotypic Disease Network (PDN):


Hypertension, Essential

Graphical network of the top 20 diseases related to Ocular Motility Disease:



Diseases related to Ocular Motility Disease
Sources

Symptoms & Phenotypes for Ocular Motility Disease

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UMLS symptoms related to Ocular Motility Disease:


ophthalmoplegia, eye manifestations, hyperexplexia, deficiencies of smooth pursuit movements, spasm of conjugate gaze, anomalies of divergence, pseudoophthalmoplegia, smooth pursuit deficiency

MGI Mouse Phenotypes related to Ocular Motility Disease:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.36 CHN1 MTM1 PHOX2A POLG ROBO3 RYR1
Sources

Drugs & Therapeutics for Ocular Motility Disease

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Drugs for Ocular Motility Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 209)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dopamine Approved Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable 62-31-7, 51-61-6 681
2
Povidone Approved Phase 4,Not Applicable 9003-39-8
3
Povidone-iodine Approved Phase 4,Not Applicable 25655-41-8
4
Iodine Approved, Investigational Phase 4,Not Applicable 7553-56-2 807
5
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 4,Phase 3 1177-87-3
6
Moxifloxacin Approved, Investigational Phase 4 354812-41-2, 151096-09-2 152946
7
Dexamethasone Approved, Investigational, Vet_approved Phase 4,Phase 3 50-02-2 5743
8
Rimexolone Approved Phase 4 49697-38-3 39507
9
Fluorometholone Approved, Investigational Phase 4 426-13-1 9878
10
Desflurane Approved Phase 4 57041-67-5 42113
11
tannic acid Approved Phase 4,Not Applicable 1401-55-4
12
Benzocaine Approved, Investigational Phase 4,Not Applicable 94-09-7, 1994-09-7 2337
13
Acetylcholine Approved, Investigational Phase 4,Phase 3,Not Applicable 51-84-3 187
14
Brinzolamide Approved Phase 4 138890-62-7 68844
15
Gabapentin Approved, Investigational Phase 4,Phase 2,Not Applicable 60142-96-3 3446
16
Memantine Approved, Investigational Phase 4,Phase 2,Not Applicable 19982-08-2 4054
17
Dexmedetomidine Approved, Vet_approved Phase 4,Not Applicable 113775-47-6 68602 5311068
18
Midazolam Approved, Illicit Phase 4,Not Applicable 59467-70-8 4192
19 Anesthetics Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
20 Pharmaceutical Solutions Phase 4,Phase 1,Phase 2,Not Applicable
21 Central Nervous System Depressants Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable
22 Autonomic Agents Phase 4,Phase 3,Not Applicable
23 Peripheral Nervous System Agents Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable
24 Anesthetics, General Phase 4,Phase 2,Not Applicable
25 Anesthetics, Inhalation Phase 4,Not Applicable
26 Cholinergic Agents Phase 4,Phase 3,Phase 2,Not Applicable
27 Neurotransmitter Agents Phase 4,Phase 3,Phase 2,Not Applicable
28 Analgesics Phase 4,Phase 2,Phase 1,Not Applicable
29 Dopamine Agents Phase 4,Phase 3,Phase 2,Not Applicable
30 Adrenergic Agents Phase 4,Phase 3,Not Applicable
31 Hypnotics and Sedatives Phase 4,Phase 2,Not Applicable
32 Anesthetics, Intravenous Phase 4,Phase 2,Not Applicable
33 Adjuvants, Anesthesia Phase 4,Phase 3,Not Applicable
34 Anti-Infective Agents, Local Phase 4,Not Applicable
35 Trace Elements Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable
36 Ophthalmic Solutions Phase 4,Not Applicable
37 Micronutrients Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable
38 Anti-Infective Agents Phase 4,Not Applicable
39 Nutrients Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable
40 Plasma Substitutes Phase 4,Not Applicable
41 Blood Substitutes Phase 4,Not Applicable
42 cadexomer iodine Phase 4,Not Applicable
43 glucocorticoids Phase 4,Phase 3
44 Hormone Antagonists Phase 4,Phase 3
45 BB 1101 Phase 4,Phase 3
46 HIV Protease Inhibitors Phase 4,Phase 3
47 Gastrointestinal Agents Phase 4,Phase 3
48 Hormones Phase 4,Phase 3
49 Antineoplastic Agents, Hormonal Phase 4,Phase 3
50 Anti-Inflammatory Agents Phase 4,Phase 3,Phase 1

Interventional clinical trials:

(show top 50) (show all 231)
# Name Status NCT ID Phase Drugs
1 The Effect of Povidone-iodine Ophthalmic Surgical Prep Solution on Respiration in Children Undergoing Strabismus Surgery With General Anesthesia. Completed NCT03349515 Phase 4 Provodine-Iodine Solution;Group B will receive three drops in each eye of ophthalmic balanced salt solution.
2 Ocular-hypertensive Response to Topical Steroids in Children After Bilateral Strabismus Surgery Completed NCT02816905 Phase 4 0.1 % Dexamethasone;0.1% Fluorometholone;1% Rimexolone
3 The Effect of Anaesthesia Depth on Oculo-cardiac Reflex Completed NCT02379546 Phase 4 Desflurane
4 Comparison of Two Treatments for Strabismus Correction: Botulinum Toxin A Associated to Surgery and Surgery Alone Completed NCT01460355 Phase 4 Botulinum Toxin Type A;saline solution
5 Povidone-iodine Antisepsis for Strabismus Surgery Completed NCT00461656 Phase 4 Preoperative conjunctival irrigation with 5% or 1.25% PI
6 Topical Brinzolamide Ophthalmic Suspension Versus Placebo in the Treatment of Infantile Nystagmus Syndrome Completed NCT01312402 Phase 4 topical brinzolamide 1% in 5mL ophthalmic medication;Placebo in 5 mL dispenser
7 Treatment of Pendular Nystagmus in OPT Completed NCT02466191 Phase 4 Memantine;Gabapentin
8 Efficacy of Single-Shot Dexmedetomidine Versus Placebo in Preventing Pediatric Emergence Delirium in Strabismus Surgery Completed NCT01901588 Phase 4 Dexmedetomidine
9 Effects of Dexmedetomidine Premedication on Emergence Agitation After Strabismus Surgery in Children Completed NCT01895023 Phase 4 Dexmedetomidine;Midazolam;Saline
10 Convergence Insufficiency Treatment Trial (CITT) Unknown status NCT00338611 Phase 3
11 A Trial of Bifocals in Myopic Children With Esophoria Unknown status NCT00000128 Phase 3
12 Vision In Preschoolers Study (VIP Study) Unknown status NCT00038753 Phase 3
13 Randomized Trial of Treatments for Convergence Insufficiency Completed NCT00347945 Phase 3
14 A Randomized Trial of Base-in Prism Reading Glasses Convergence Insufficiency in Children Completed NCT00347581 Phase 3
15 Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus Completed NCT01584843 Phase 3 GSK1358820
16 The Prism Adaptation Study (PAS) Completed NCT00000121 Phase 3
17 Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy Completed NCT01110720 Phase 2, Phase 3 Davunetide;Placebo
18 Effects of Prismatic Spectacle Lenses on Symptoms of Dizziness, Headache and Anxiety as Caused by Vertical Heterophoria Completed NCT00785135 Phase 3
19 Effects of Coenzyme Q10 in PSP and CBD Completed NCT00532571 Phase 2, Phase 3 CoQ10
20 Effects of Coenzyme Q10 in Progressive Supranuclear Palsy (PSP) Completed NCT00382824 Phase 2, Phase 3 CoenzymeQ10
21 Amblyopia (Lazy Eye) Treatment Study Completed NCT00001864 Phase 3 Atropine
22 The Effect of Slanted Recession of Horizontal Muscle on Horizontal Strabismus With Abnormal Accommodative Convergence /Accommodation Ratio (AC/A) Recruiting NCT03555045 Phase 2, Phase 3
23 Botox Instead of Strabismus Surgery (BISS) Recruiting NCT03459092 Phase 3 Botulinum toxin type A
24 Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg)Opsoclonus Myoclonus Syndrome/Dancing Eye Syndrome (OMS/DES) in Children With and Without Neuroblastoma (NBpos and NBneg) Recruiting NCT01868269 Phase 3 Dexamethasone acetate;dexamethasone and cyclophosphamide;dexamethasone and rituximab
25 Bupivacaine Injection of Eye Muscles to Treat Strabismus Recruiting NCT01616108 Phase 2, Phase 3 Bupivacaine
26 Efficacy of RIVAstigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy Recruiting NCT02839642 Phase 3 Rivastigmine;Placebo
27 Office-based Vision Therapy for Improving Reading and Attention in Children With Convergence Insufficiency Active, not recruiting NCT02207517 Phase 3
28 Comparison of Medial Rectus Resection and Plication in Exotropic Patients Not yet recruiting NCT03768362 Phase 2, Phase 3
29 Efficacy, Tolerability and Safety of Azilect in Subjects With Progressive Supranuclear Palsy Terminated NCT01187888 Phase 3 Rasagiline;Sugar pill
30 Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS) Terminated NCT00211224 Phase 3 Riluzole
31 Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma Unknown status NCT00202930 Phase 2 anti-CD20 (Rituximab)
32 Grading Versus Classic Inferior Oblique Anterior Transposition in Patient With Asymmetric Dissociated Vertical Deviation Unknown status NCT03135938 Phase 1, Phase 2
33 Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism Unknown status NCT01824121 Phase 1, Phase 2
34 4-Aminopyridine in Episodic Ataxia Type 2 Unknown status NCT01543750 Phase 2 4-Aminopyridine;Placebo
35 Efficacy Study for Treatment of Dementia in Progressive Supranuclear Palsy Unknown status NCT00522015 Phase 2 rivastigmine
36 Study of the Distractibility Syndrome in Patients With Progressive Supranuclear Palsy Unknown status NCT00139373 Phase 2 donepezil
37 Effectiveness of Rituximab in Pediatric OMS Patients. Completed NCT00244361 Phase 1, Phase 2 rituximab
38 Prevention of Complications of Eye Surgery Completed NCT00478907 Phase 2 KETAMINE, PROPOFOL, THIOPENTAL
39 Efficacy and Safety Study of Neramexane to Treat Congenital and Acquired Nystagmus Completed NCT00661440 Phase 2 Neramexane mesylate
40 Eye Muscle Surgery to Treat Congenital Nystagmus Completed NCT00001866 Phase 2
41 Treatment of Pendular Nystagmus With Gabapentin and Memantine in Patients With Multiple Sclerosis Completed NCT01744444 Phase 2 Memantine;Gabapentin
42 Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy Completed NCT01537549 Phase 1, Phase 2 alpha-lipoic acid and L-acetyl carnitine
43 Davunetide (AL-108) in Predicted Tauopathies - Pilot Study Completed NCT01056965 Phase 2 davunetide (AL-108, NAP);Placebo nasal spray
44 A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration Completed NCT00703677 Phase 1, Phase 2 Lithium
45 Trial of Valproic Acid in Patients With Progressive Supranuclear Palsy (Depakine) Completed NCT00385710 Phase 2 valproic acid;Placebo
46 Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy Completed NCT00328874 Phase 2 Coenzyme Q10
47 Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) to Treat Progressive Supranuclear Palsy Completed NCT00005903 Phase 2 GDNF & Synchro Med Infusion System
48 Comparison of Three Vision Therapy Approaches for Convergence Insufficiency Recruiting NCT03431454 Phase 2
49 An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP) Recruiting NCT03391765 Phase 2 ABBV-8E12
50 Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis Active, not recruiting NCT02391961 Phase 2 Dalfampridine;Placebo

Search NIH Clinical Center for Ocular Motility Disease

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Genetic Tests for Ocular Motility Disease

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Genetic tests related to Ocular Motility Disease:

# Genetic test Affiliating Genes
1 Abnormality of Eye Movement 30
Sources

Anatomical Context for Ocular Motility Disease

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MalaCards organs/tissues related to Ocular Motility Disease:

42
Eye, Brain, Testes, Colon, Bone, Bone Marrow
Sources

Publications for Ocular Motility Disease

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Articles related to Ocular Motility Disease:

(show all 22)
# Title Authors Year
1
Development of a core outcome set for amblyopia, strabismus and ocular motility disorders: a review to identify outcome measures. ( 30736755 )
2019
2
Correction to: development of a core outcome set for amblyopia, strabismus and ocular motility disorders: a review to identify outcome measures. ( 30857536 )
2019
3
A cohort study on acute ocular motility disorders in pediatric emergency department. ( 29843812 )
2018
4
Burden of Ocular Motility Disorders at a Tertiary Care Institution: A Case to Enhance Secondary Level Eye Care. ( 27051084 )
2016
5
Congenital and Genetic Ocular Motility Disorders: Update and Considerations. ( 26564928 )
2015
6
The use of dynamic magnetic resonance in the diagnosis of ocular motility disorders. ( 21853952 )
2011
7
Surgical treatment of vertical ocular motility disorders of supranuclear origin. ( 22069848 )
2011
8
Analysis of the CHN1 gene in patients with various types of congenital ocular motility disorders. ( 20535495 )
2010
9
Overview and comparison of screen test methods used in quantifying ocular motility disorders. ( 21149143 )
2006
10
Applications of molecular genetics to the understanding of congenital ocular motility disorders. ( 11960793 )
2002
11
Refractive errors and ocular motility disorders in preterm babies with and without retinopathy of prematurity. ( 10516517 )
1999
12
Surgical treatment of supranuclear and internuclear ocular motility disorders. ( 9373480 )
1997
13
Original papers: Ocular motility disorders after surgery for retinitis pigmentosa 'Cuba-therapy'. ( 21314532 )
1995
14
Video loop MRI of ocular motility disorders. ( 7822545 )
1995
15
Ocular motility disorders secondary to sinus surgery. ( 8443115 )
1993
16
Botulinum toxin treatment of supranuclear ocular motility disorders. ( 1620351 )
1992
17
Ocular motility disorders and orbital trauma. ( 1639595 )
1992
18
Prevalence of refractive errors and ocular motility disorders in 5- to 10-year-old Swedish children born prematurely or at full-term. ( 2618642 )
1989
19
Intraocular pressure changes in secondary positions of gaze in normal subjects and in restrictive ocular motility disorders. ( 3342982 )
1988
20
Magnetic resonance imaging of the posterior fossa in ocular motility disorders--four case studies. ( 2963030 )
1987
21
Computed tomography scanning in the evaluation of ocular motility disorders. ( 3299474 )
1987
22
Ultrastructural studies of extraocular muscles in ocular motility disorders. II. Morphological analysis of 38 biopsies. ( 215049 )
1978
Sources

Variations for Ocular Motility Disease

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ClinVar genetic disease variations for Ocular Motility Disease:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 46;XY;t(4;14)(p14;q11.2)dn Translocation Uncertain significance
Sources

Expression for Ocular Motility Disease

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Search GEO for disease gene expression data for Ocular Motility Disease.
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Pathways for Ocular Motility Disease

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GO Terms for Ocular Motility Disease

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Cellular components related to Ocular Motility Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 I band GO:0031674 8.62 MTM1 RYR1

Biological processes related to Ocular Motility Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial genome maintenance GO:0000002 9.26 SLC25A4 TYMP
2 pyrimidine nucleoside catabolic process GO:0046135 9.16 NT5C3A TYMP
3 mitochondrial DNA replication GO:0006264 8.96 POLG TWNK
4 pyrimidine nucleoside metabolic process GO:0006213 8.62 NT5C3A TYMP

Molecular functions related to Ocular Motility Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protease binding GO:0002020 8.8 POLG RYR1 TWNK
Sources

Sources for Ocular Motility Disease

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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