LCA4
MCID: LBR014
MIFTS: 56

Leber Congenital Amaurosis 4 (LCA4)

Categories: Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leber Congenital Amaurosis 4

MalaCards integrated aliases for Leber Congenital Amaurosis 4:

Name: Leber Congenital Amaurosis 4 57 12 20 72 29 6 15 70
Lca4 57 12 20 72
Retinitis Pigmentosa, Juvenile 57 29 6
Amaurosis Congenita of Leber, Type 4 20
Leber Congenital Amaurosis, Type 4 39
Leber Congenital Amaurosis Type 4 20
Retinitis Pigmentosa 70
Cone-Rod Dystrophy 57

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
keratoconus, which was observed in 1 family, might be secondary to eye rubbing due to lca
later onset cord and rp seen in heterozygotes


HPO:

31
leber congenital amaurosis 4:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110332
OMIM® 57 604393
OMIM Phenotypic Series 57 PS204000
MeSH 44 D057130
ICD10 32 H35.5
UMLS 70 C0035334 C1858386

Summaries for Leber Congenital Amaurosis 4

OMIM® : 57 Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Various intermediate phenotypes between LCA and retinitis pigmentosa are known and are sometimes described as 'early-onset severe rod-cone dystrophy' or 'early-onset retinal degeneration' (Booij et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000; for cone-rod dystrophy, see 120970. (604393) (Updated 05-Apr-2021)

MalaCards based summary : Leber Congenital Amaurosis 4, also known as lca4, is related to cone-rod dystrophy 12 and cone-rod dystrophy 3. An important gene associated with Leber Congenital Amaurosis 4 is AIPL1 (Aryl Hydrocarbon Receptor Interacting Protein Like 1), and among its related pathways/superpathways are Metabolism of fat-soluble vitamins and Visual Cycle in Retinal Rods. The drugs Tocopherol and Vitamin E have been mentioned in the context of this disorder. Affiliated tissues include retina, eye and bone marrow, and related phenotypes are keratoconus and blindness

Disease Ontology : 12 A Leber congenital amaurosis that is characterized by a relatively severe phenotype, with maculopathy and marked bone-spicule pigmentary retinopathy in most and keratoconus and cataract in a large subset and that has material basis in mutation in the AIPL1 gene on chromosome 17p13.

UniProtKB/Swiss-Prot : 72 Leber congenital amaurosis 4: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.

Related Diseases for Leber Congenital Amaurosis 4

Diseases in the Leber Congenital Amaurosis 4 family:

Leber Congenital Amaurosis 1 Leber Congenital Amaurosis 2
Leber Congenital Amaurosis 3 Leber Congenital Amaurosis 5
Leber Congenital Amaurosis 9 Leber Congenital Amaurosis 12
Leber Congenital Amaurosis 10 Leber Congenital Amaurosis 13
Leber Congenital Amaurosis 14 Leber Congenital Amaurosis 6
Leber Congenital Amaurosis 7 Leber Congenital Amaurosis 8
Leber Congenital Amaurosis 11 Leber Congenital Amaurosis 15
Leber Congenital Amaurosis 16 Leber Congenital Amaurosis 17
Leber Congenital Amaurosis 19

Diseases related to Leber Congenital Amaurosis 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 206)
# Related Disease Score Top Affiliating Genes
1 cone-rod dystrophy 12 33.3 GUCY2D AIPL1
2 cone-rod dystrophy 3 33.2 GUCY2D CRX
3 cone-rod dystrophy 17 33.2 GUCY2D AIPL1
4 cone-rod dystrophy 8 33.0 LCA5 GUCY2D AIPL1
5 cone-rod dystrophy 13 32.5 SPATA7 RPGRIP1 IQCB1
6 leber congenital amaurosis 14 31.5 SPATA7 RDH12 LRAT LCA5 IQCB1 AIPL1
7 yemenite deaf-blind hypopigmentation syndrome 31.1 RPE65 GUCY2D CEP290 AIPL1
8 stargardt disease 1 31.0 TULP1 CRX CRB1
9 cone-rod dystrophy 6 31.0 RPGRIP1 RPE65 RD3 PDE6C PDE6A IQCB1
10 scotoma 30.9 RPE65 GUCY2D CRB1
11 retinitis 30.7 RPGRIP1 RPE65 PDE6A IMPDH1 CRB1
12 night blindness 30.6 RPE65 LRAT GUCY2D CRB1 CEP290
13 achromatopsia 3 30.1 RPGRIP1 PDE6C GUCY2D
14 macular degeneration, age-related, 1 30.0 RPE65 RDH12 LRAT GUCY2D CRX CRB1
15 nephronophthisis 4 30.0 RPGRIP1 PDE6A
16 leber congenital amaurosis 7 29.9 SPATA7 RDH12 LCA5 IMPDH1 GUCY2D CRX
17 color blindness 29.7 RPGRIP1 RPE65 PDE6C PDE6A GUCY2D AIPL1
18 hereditary retinal dystrophy 29.7 RPE65 PDE6A GUCY2D CRX CRB1
19 coloboma of macula 29.5 IQCB1 CRX CRB1 CEP290
20 nephronophthisis 29.3 SPATA7 RPGRIP1 LCA5 IQCB1 CEP290
21 bardet-biedl syndrome 29.3 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PDE6A
22 leber congenital amaurosis 5 29.0 TULP1 SPATA7 RPGRIP1 RDH12 RD3 LRAT
23 leber congenital amaurosis 8 28.9 TULP1 SPATA7 RPE65 RDH12 LCA5 IMPDH1
24 leber congenital amaurosis 10 28.9 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
25 stargardt disease 28.9 TULP1 SPATA7 RPE65 RDH12 PDE6A LRAT
26 retinal degeneration 28.9 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
27 cone-rod dystrophy 2 28.8 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
28 eye disease 28.8 RPGRIP1 RPE65 RDH12 IQCB1 GUCY2D CRX
29 leber congenital amaurosis 1 28.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
30 leber congenital amaurosis 3 28.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
31 pathologic nystagmus 28.6 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PDE6C
32 retinal disease 28.5 TULP1 RPGRIP1 RPE65 RDH12 PDE6A LRAT
33 cone dystrophy 28.3 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 PDE6C
34 leber congenital amaurosis 9 28.3 TULP1 SPATA7 RPE65 RDH12 LRAT LCA5
35 usher syndrome 27.5 TULP1 RPGRIP1 RPE65 RDH12 PDE6A LRAT
36 achromatopsia 27.4 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
37 keratoconus 27.2 TULP1 SPATA7 RPE65 RDH12 RD3 LRAT
38 congenital stationary night blindness 27.1 TULP1 RPGRIP1 RPE65 RDH12 RD3 PDE6C
39 leber plus disease 27.0 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
40 retinitis pigmentosa 26.8 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
41 fundus dystrophy 26.7 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
42 spondylometaphyseal dysplasia with cone-rod dystrophy 12.0
43 cone-rod dystrophy, x-linked, 1 11.9
44 jalili syndrome 11.9
45 cone-rod dystrophy, x-linked, 3 11.9
46 cone-rod dystrophy and hearing loss 1 11.9
47 cone-rod dystrophy 5 11.9
48 cone-rod dystrophy 16 11.9
49 cone-rod dystrophy 18 11.9
50 cone-rod dystrophy 20 11.9

Graphical network of the top 20 diseases related to Leber Congenital Amaurosis 4:



Diseases related to Leber Congenital Amaurosis 4

Symptoms & Phenotypes for Leber Congenital Amaurosis 4

Human phenotypes related to Leber Congenital Amaurosis 4:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 keratoconus 31 occasional (7.5%) HP:0000563
2 blindness 31 HP:0000618
3 reduced visual acuity 31 HP:0007663
4 nyctalopia 31 HP:0000662
5 optic disc pallor 31 HP:0000543
6 cone/cone-rod dystrophy 31 HP:0000548
7 macular atrophy 31 HP:0007401
8 attenuation of retinal blood vessels 31 HP:0007843
9 pendular nystagmus 31 HP:0012043
10 undetectable light- and dark-adapted electroretinogram 31 HP:0007688

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
macular atrophy
pendular nystagmus
pale optic disc
poor central vision or blindness from birth
keratoconus (in some patients)
more

Clinical features from OMIM®:

604393 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.3 GUCY2D
2 Decreased viability GR00055-A-2 10.3 GUCY2D
3 Decreased viability GR00221-A-1 10.3 GUCY2D RPGRIP1
4 Decreased viability GR00221-A-2 10.3 GUCY2D RPGRIP1
5 Decreased viability GR00221-A-3 10.3 GUCY2D
6 Decreased viability GR00221-A-4 10.3 GUCY2D RPGRIP1
7 Decreased viability GR00240-S-1 10.3 GUCY2D
8 Decreased viability GR00249-S 10.3 CA4 CRX GUCY2D
9 Decreased viability GR00301-A 10.3 RPGRIP1
10 Decreased viability GR00381-A-1 10.3 LRAT RPGRIP1
11 Decreased viability GR00386-A-1 10.3 CA4 CRX GUCY2D IMPDH1 IQCB1 LCA5
12 Decreased viability GR00402-S-2 10.3 GUCY2D LCA5 RDH12 SPATA7
13 Increased viability GR00386-A-1 8.8 CEP290 PDE6C RDH12
14 Increased the percentage of infected cells GR00402-S-1 8.65 RDH12

MGI Mouse Phenotypes related to Leber Congenital Amaurosis 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.03 AIPL1 CEP290 CRB1 CRX GUCY2D LCA5
2 vision/eye MP:0005391 9.55 AIPL1 CA4 CEP290 CRB1 CRX GUCY2D
3 pigmentation MP:0001186 9.43 CEP290 CRB1 CRX LCA5 RPE65 TULP1

Drugs & Therapeutics for Leber Congenital Amaurosis 4

Drugs for Leber Congenital Amaurosis 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 105)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Tocopherol Approved, Investigational Phase 3 1406-66-2
2
Vitamin E Approved, Nutraceutical, Vet_approved Phase 3 59-02-9 14985
3
Vitamin A Approved, Nutraceutical, Vet_approved Phase 3 68-26-8, 11103-57-4 445354
4
Vitamin D Approved, Nutraceutical, Vet_approved Phase 3 1406-16-2
5
Lutein Approved, Investigational, Nutraceutical Phase 3 127-40-2 5281243
6
Beta carotene Approved, Nutraceutical Phase 2, Phase 3 7235-40-7 5280489
7 Tocotrienol Investigational Phase 3 6829-55-6
8 Retinol palmitate Phase 3
9 retinol Phase 3
10 Tocotrienols Phase 3
11 Tocopherols Phase 3
12 Antioxidants Phase 3
13 Protective Agents Phase 3
14 Calciferol Phase 3
15 Carotenoids Phase 2, Phase 3
16 Antihypertensive Agents Phase 3
17 Isopropyl unoprostone Phase 3
18
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 2 1177-87-3
19
Dexamethasone Approved, Investigational, Vet_approved Phase 2 50-02-2 5743
20
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
21
Povidone Approved Phase 2 9003-39-8 131751496
22
Povidone-iodine Approved Phase 2 25655-41-8
23
Ciprofloxacin Approved, Investigational Phase 2 85721-33-1 2764
24
Iodine Approved, Investigational Phase 2 7553-56-2 807
25
Dopamine Approved Phase 2 62-31-7, 51-61-6 681
26
Carbidopa Approved Phase 2 28860-95-9 34359
27
Levodopa Approved Phase 2 59-92-7 6047
28
Sodium citrate Approved, Investigational Phase 2 68-04-2
29
Minocycline Approved, Investigational Phase 2 10118-90-8 5281021
30
Hydroxychloroquine Approved Phase 1, Phase 2 118-42-3 3652
31
Adapalene Approved Phase 1, Phase 2 106685-40-9 60164
32
Citric acid Approved, Nutraceutical, Vet_approved Phase 2 77-92-9 311
33
Cadexomer iodine Experimental Phase 2 94820-09-4
34 Gastrointestinal Agents Phase 2
35 Antiemetics Phase 2
36 Hormone Antagonists Phase 2
37 Hormones Phase 2
38 glucocorticoids Phase 2
39 Antineoplastic Agents, Hormonal Phase 2
40 Anti-Inflammatory Agents Phase 2
41 BB 1101 Phase 2
42 Omega 3 Fatty Acid Phase 2
43 Anticonvulsants Phase 2
44 Psychotropic Drugs Phase 2
45 Soy Bean Phase 2
46 Pharmaceutical Solutions Phase 2
47 Ophthalmic Solutions Phase 2
48 Proxymetacaine Phase 2
49 Mitogens Phase 2
50 Adrenergic alpha-Agonists Phase 1, Phase 2

Interventional clinical trials:

(show top 50) (show all 179)
# Name Status NCT ID Phase Drugs
1 Role of Capsular Tension Ring in Anterior Capsular Contraction in Retinitis Pigmentosa Patients Completed NCT00717080 Phase 4
2 Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa Completed NCT00000114 Phase 3 Vitamin E;Vitamin A
3 Randomized Clinical Trial for Retinitis Pigmentosa Completed NCT00346333 Phase 3 Lutein
4 Randomized Trial for Retinitis Pigmentosa Completed NCT00000116 Phase 3 Vitamin A;Nutritional Supplement
5 Management of Retinitis Pigmentosa by Wharton's Jelly Derived Mesenchymal Stem Cells: Preliminary Clinical Results Completed NCT04224207 Phase 3
6 Cord Blood Platelet-rich Plasma (CB-PRP) in Retinitis Pigmentosa Recruiting NCT04636853 Phase 3
7 The Effect of Oral Administration of 9-cis β Carotene Rich Powder of the Alga Dunaliella Bardawil on Visual Functions in Patients With Retinitis Pigmentosa Recruiting NCT01680510 Phase 2, Phase 3
8 Phase 3 Randomized, Controlled Study of AAV5-RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene Not yet recruiting NCT04671433 Phase 3
9 Follow-up Phase 3 Randomized, Controlled Study of AAV5-RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene Not yet recruiting NCT04794101 Phase 3
10 Phase III Clinical Study of UF-021 for Retinitis Pigmentosa - Evaluation for a Comparative Double Masked Placebo Controlled Study Period and a Continuous Administration Period Terminated NCT01786395 Phase 3 UF-021;Placebo
11 Argus® II Retinal Stimulation System Feasibility Protocol Unknown status NCT00407602 Phase 2
12 An Open Labeled Clinical Study to Evaluate the Safety and Efficacy OF Autologous Bone Marrow Derived Mono Nuclear Stem Cell (BMMNCs) in Retinitis Pigmentosa. It is Self Funded (Patients' Own Funding) Clinical Trial Unknown status NCT01914913 Phase 1, Phase 2
13 Dexamethasone in Retinitis Pigmentosa Cystoid Macular Edema Unknown status NCT02804360 Phase 2
14 Photoreceptor Structure in A Phase 2 Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Rates of Change in Cone Spacing and Density Unknown status NCT01530659 Phase 2 NT-501
15 Prospective Non-randomised Exploratory Study to Assess the Safety and Efficacy of Aflibercept (Eylea) in Cystoid Macular Oedema (CMO) Associated With Retinitis Pigmentosa (RP) Unknown status NCT02661711 Phase 2 Aflibercept
16 An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1) Completed NCT01461213 Phase 1, Phase 2 rAAV2.REP1
17 A Phase II Multiple Site, Randomized, Placebo-Controlled Trial of Oral Valproic Acid for Autosomal Dominant Retinitis Pigmentosa Completed NCT01233609 Phase 2 Valproic Acid;Placebo
18 A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR) Completed NCT03116113 Phase 1, Phase 2
19 Investigation of Effectiveness and Safety of High Dose Docosahexaenoic Acid (DHA) in X-Linked Retinitis Pigmentosa Completed NCT00100230 Phase 2 docosahexaenoic acid OR corn/soy oil placebo
20 Safety Study in Retinal Transplantation for Retinitis Pigmentosa. Completed NCT00345917 Phase 2
21 Effects of Lutein in Retinitis Pigmentosa Completed NCT00029289 Phase 1, Phase 2 Lutein (10 or 30 mg/day) capsules
22 A Prospective, Multicenter, Open-Label, Single-Arm Study of the Safety and Tolerability of a Single, Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa (RP) Completed NCT02320812 Phase 1, Phase 2
23 A Phase II/III Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Visual Acuity as the Primary Outcome Completed NCT00447993 Phase 2 NT-501;NT-501
24 A Phase II/III Study of Encapsulated Human NTC-201 Cell Implants Releasing Ciliary Neurotrophic Factor (CNTF) for Participants With Retinitis Pigmentosa Using Visual Field Sensitivity as the Primary Outcome Completed NCT00447980 Phase 2 NT-501;NT-501
25 Pilot Study to Evaluate Oral Minocycline in the Treatment of Cystoid Macular Edema Associated With Retinitis Pigmentosa Completed NCT02140164 Phase 1, Phase 2 Minocycline
26 Safety Issues of Peribulbar Injection of Umbilical Cord Mesenchymal Stem Cell (UC-MSC) in Patients With Retinitis Pigmentosa Completed NCT04315025 Phase 1, Phase 2
27 An Exploratory Study to Evaluate the Safety of Brimonidine Intravitreal Implant in Patients With Retinitis Pigmentosa Completed NCT00661479 Phase 1, Phase 2 400 µg Brimonidine Tartrate Implant;200 µg Brimonidine Tartrate Implant;100 µg Brimonidine Tartrate Implant
28 Phase 2 Study Of Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa Completed NCT01560715 Phase 2
29 Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa Completed NCT01399515 Phase 2 Valproic Acid
30 Nerve Growth Factor Eye Drops as a Novel Treatment for Vision Loss in Patients With Retinitis Pigmentosa: From Preclinical to Clinical Phase II Trial Completed NCT02609165 Phase 2 rhNGF 180 µg/ml eye drops solution;vehicle eye drops
31 A 24 Week Phase Ib/II, Multicenter, Randomized, Controlled, Parallel Group, Dose Ranging Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of 2 Doses (60, 180 µg/ml) of rhNGF Solution vs Vehicle in Patients With RP. Completed NCT02110225 Phase 1, Phase 2 rhNGF 60 µg/ml eye drops solution;rhNGF 180 µg/ml eye drops solution;Placebo
32 An Open-label, Phase 1/2 Trial of Gene Therapy 4D-125 in Males With X-linked Retinitis Pigmentosa (XLRP) Caused by Mutations in the RPGR Gene Recruiting NCT04517149 Phase 1, Phase 2
33 Investigation of Therapeutic Efficacy and Safety of Umbilical Cord Derived Mesenchymal Stem Cells (UMSCs) for the Management of Retinitis Pigmentosa (RP) Recruiting NCT04763369 Phase 2
34 A First-in-Human Study to Evaluate the Safety and Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene Recruiting NCT03780257 Phase 1, Phase 2 QR-421a
35 STREAM: A Phase 1/2, Open-label, Safety, Tolerability and Preliminary Efficacy Study of Implantation Into One Eye of hESC-derived RPE in Patients With Retinitis Pigmentosa Due to Monogenic Mutation Recruiting NCT03963154 Phase 1, Phase 2
36 The Effect of L-Dopa on the Progression of Retinitis Pigmentosa Recruiting NCT02837640 Phase 2 levodopa-carbidopa
37 Safety and Efficacy of NPI-001 Tablets Versus Placebo for Treatment of Retinitis Pigmentosa Associated With Usher Syndrome Recruiting NCT04355689 Phase 1, Phase 2 NPI-001
38 PIGMENT - PDE6A Gene Therapy for Retinitis Pigmentosa Recruiting NCT04611503 Phase 1, Phase 2 subretinal injection of rAAV.hPDE6A
39 Safety and Efficacy of a Unilateral Subretinal Administration of HORA-PDE6B in Patients With Retinitis Pigmentosa Harbouring Mutations in the PDE6B Gene Leading to a Defect in PDE6ß Expression Recruiting NCT03328130 Phase 1, Phase 2
40 A Phase 1/2a, Open-Label, Non-Randomized, Dose-Escalation Study to Evaluate the Safety and Tolerability of GS030 in Subjects With Retinitis Pigmentosa Recruiting NCT03326336 Phase 1, Phase 2
41 A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene Recruiting NCT04123626 Phase 1, Phase 2 QR-1123
42 Phase 1/2, Safety and Efficacy Trial of BS01, a Recombinant Adeno-Associated Virus Vector Expressing ChronosFP in Patients With Retinitis Pigmentosa Recruiting NCT04278131 Phase 1, Phase 2 BS01
43 The Efficacy and Safety of Oral Minocycline in the Treatment of Retinitis Pigmentosa: An Open-label Clinical Trial Recruiting NCT04068207 Phase 2 Minocycline
44 Oral Hydroxychloroquine for Retinitis Pigmentosa Caused by P23H-RHO (Substitution of Proline to Histidine at Codon 23 of the Rhodopsin Protein) Recruiting NCT04120883 Phase 1, Phase 2 Hydroxychloroquine lower dose;Hydroxychloroquine higher dose
45 First-in-human Phase I/IIa, Open-Label, Prospective Study of the Safety and Tolerability of Subretinally Transplanted Human Retinal Progenitor Cells (hRPC) in Patients With Retinitis Pigmentosa (RP) Recruiting NCT02464436 Phase 1, Phase 2 hRPC
46 An Open-label First-in-human Single Ascending Dose Study to Explore Safety, Tolerability and Efficacy of Subretinal Administration of CPK850 Gene Therapy in Patients With Retinitis Pigmentosa Due to Mutations in the Retinaldehyde Binding Protein 1 (RLBP1) Gene Recruiting NCT03374657 Phase 1, Phase 2
47 An Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations Recruiting NCT03316560 Phase 1, Phase 2
48 Sildenafil for Treatment of Choroidal Ischemia Recruiting NCT04356716 Phase 2 Sildenafil
49 Phase I/IIa, Open-Label, Dose-Escalation Study of Safety and Tolerability of Intravitreal RST-001 in Patients With Advanced Retinitis Pigmentosa (RP) Active, not recruiting NCT02556736 Phase 1, Phase 2 RST-001
50 An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2-.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR) Active, not recruiting NCT03252847 Phase 1, Phase 2

Search NIH Clinical Center for Leber Congenital Amaurosis 4

Genetic Tests for Leber Congenital Amaurosis 4

Genetic tests related to Leber Congenital Amaurosis 4:

# Genetic test Affiliating Genes
1 Leber Congenital Amaurosis 4 29 AIPL1
2 Retinitis Pigmentosa, Juvenile 29

Anatomical Context for Leber Congenital Amaurosis 4

MalaCards organs/tissues related to Leber Congenital Amaurosis 4:

40
Retina, Eye, Bone Marrow, Bone, Pineal

Publications for Leber Congenital Amaurosis 4

Articles related to Leber Congenital Amaurosis 4:

(show all 36)
# Title Authors PMID Year
1
Prevalence of AIPL1 mutations in inherited retinal degenerative disease. 61 57 6
10873396 2000
2
Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. 61 6 57
10615133 2000
3
Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy. 6 57
25596619 2015
4
Interaction of aryl hydrocarbon receptor-interacting protein-like 1 with the farnesyl moiety. 6 61
23737531 2013
5
Evaluation of Italian patients with leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. 6 61
21474771 2011
6
A novel locus for Leber congenital amaurosis (LCA4) with anterior keratoconus mapping to chromosome 17p13. 61 57
10711674 2000
7
The integrity and organization of the human AIPL1 functional domains is critical for its role as a HSP90-dependent co-chaperone for rod PDE6. 6
28973376 2017
8
The genetic profile of Leber congenital amaurosis in an Australian cohort. 6
29178642 2017
9
Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client. 6
27268253 2016
10
Investigation of Aberrant Splicing Induced by AIPL1 Variations as a Cause of Leber Congenital Amaurosis. 6
26650897 2015
11
Whole Exome Sequencing Reveals Mutations in Known Retinal Disease Genes in 33 out of 68 Israeli Families with Inherited Retinopathies. 6
26306921 2015
12
Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son. 6
24093488 2015
13
The Leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium. 6
25799540 2015
14
Genome-wide homozygosity mapping in families with leber congenital amaurosis identifies mutations in AIPL1 and RDH12 genes. 6
25148430 2014
15
Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy. 6
22412862 2012
16
The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway. 6
22347407 2012
17
Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis. 6
21153841 2011
18
Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. 6
20702822 2011
19
The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. 57
20042464 2010
20
Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors. 57
19299492 2009
21
Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. 6
17964524 2007
22
Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. 57
16272259 2005
23
Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. 6
16123401 2005
24
The Leber congenital amaurosis protein AIPL1 modulates the nuclear translocation of NUB1 and suppresses inclusion formation by NUB1 fragments. 6
15347646 2004
25
The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. 6
15249368 2004
26
Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. 6
15024725 2004
27
Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. 57
9326941 1997
28
Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis. 57
8944027 1996
29
Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1. 61
32214115 2020
30
A new novel nonsense mutation in AIPL1 in a LCA4 family. 61
31576779 2019
31
Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish. 61
28378769 2017
32
Early alteration of retinal neurons in Aipl1-/- animals. 61
24736053 2014
33
Structural studies on AIPL1 and its functional interactions with NUB1 to identify key interacting residues in LCA4. 61
24596939 2012
34
Gene symbol: AIPL1. Disease: LCA4. 61
15991325 2005
35
Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. 61
15365178 2004
36
Leber Congenital Amaurosis – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
20301475 2004

Variations for Leber Congenital Amaurosis 4

ClinVar genetic disease variations for Leber Congenital Amaurosis 4:

6 (show top 50) (show all 189)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AIPL1 NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) Deletion Pathogenic 5568 rs281865195 GRCh37: 17:6328871-6328882
GRCh38: 17:6425551-6425562
2 AIPL1 NM_014336.5(AIPL1):c.715T>C (p.Cys239Arg) SNV Pathogenic 5567 rs62637012 GRCh37: 17:6330004-6330004
GRCh38: 17:6426684-6426684
3 AIPL1 NM_014336.5(AIPL1):c.589G>C (p.Ala197Pro) SNV Pathogenic 65709 rs62637010 GRCh37: 17:6330254-6330254
GRCh38: 17:6426934-6426934
4 AIPL1 NM_014336.5(AIPL1):c.617T>A (p.Ile206Asn) SNV Pathogenic 65710 rs62637011 GRCh37: 17:6330226-6330226
GRCh38: 17:6426906-6426906
5 AIPL1 NM_014336.5(AIPL1):c.265T>C (p.Cys89Arg) SNV Pathogenic 574505 rs1264794214 GRCh37: 17:6337250-6337250
GRCh38: 17:6433930-6433930
6 AIPL1 NM_014336.5(AIPL1):c.547G>T (p.Gly183Ter) SNV Pathogenic 848588 GRCh37: 17:6330296-6330296
GRCh38: 17:6426976-6426976
7 AIPL1 NC_000017.11:g.6436899del Deletion Pathogenic 916619 GRCh37: 17:6340218-6340218
GRCh38: 17:6436898-6436898
8 AIPL1 NM_014336.5(AIPL1):c.104_105insG (p.Phe35fs) Insertion Pathogenic 916620 GRCh37: 17:6337410-6337411
GRCh38: 17:6434090-6434091
9 AIPL1 NM_014336.5(AIPL1):c.211G>T (p.Val71Phe) SNV Pathogenic 812219 rs775364986 GRCh37: 17:6337304-6337304
GRCh38: 17:6433984-6433984
10 AIPL1 NM_014336.5(AIPL1):c.96+4A>T SNV Pathogenic 916621 GRCh37: 17:6338325-6338325
GRCh38: 17:6435005-6435005
11 AIPL1 NM_014336.5(AIPL1):c.421C>T (p.Gln141Ter) SNV Pathogenic 916622 GRCh37: 17:6331682-6331682
GRCh38: 17:6428362-6428362
12 AIPL1 NM_014336.5(AIPL1):c.582C>G (p.Tyr194Ter) SNV Pathogenic 916623 GRCh37: 17:6330261-6330261
GRCh38: 17:6426941-6426941
13 AIPL1 NM_014336.5(AIPL1):c.597dup (p.Lys200fs) Duplication Pathogenic 916624 GRCh37: 17:6330245-6330246
GRCh38: 17:6426925-6426926
14 AIPL1 NM_014336.5(AIPL1):c.785-10_786del Deletion Pathogenic 916625 GRCh37: 17:6329149-6329160
GRCh38: 17:6425829-6425840
15 AIPL1 NM_014336.5(AIPL1):c.105_106insGTGATCTT (p.His36fs) Insertion Pathogenic 916627 GRCh37: 17:6337409-6337410
GRCh38: 17:6434089-6434090
16 AIPL1 NM_014336.5(AIPL1):c.97_104dup (p.Phe35delinsLeuTer) Duplication Pathogenic 916628 GRCh37: 17:6337410-6337411
GRCh38: 17:6434090-6434091
17 AIPL1 NM_014336.5(AIPL1):c.277-2A>G SNV Pathogenic 99798 rs140808549 GRCh37: 17:6331828-6331828
GRCh38: 17:6428508-6428508
18 AIPL1 NM_014336.5(AIPL1):c.466-1G>C SNV Pathogenic 916629 GRCh37: 17:6330378-6330378
GRCh38: 17:6427058-6427058
19 AIPL1 NM_014336.5(AIPL1):c.665G>A (p.Trp222Ter) SNV Pathogenic 916630 GRCh37: 17:6330054-6330054
GRCh38: 17:6426734-6426734
20 AIPL1 NM_014336.5(AIPL1):c.834G>A (p.Trp278Ter) SNV Pathogenic 5565 rs62637014 GRCh37: 17:6329101-6329101
GRCh38: 17:6425781-6425781
21 SPATA7 NC_000014.9:g.88362113_88425523delinsTGG Indel Pathogenic 635162 GRCh37:
GRCh38: 14:88362113-88425523
22 AIPL1 NM_014336.5(AIPL1):c.784G>A (p.Gly262Ser) SNV Pathogenic 65711 rs142326926 GRCh37: 17:6329935-6329935
GRCh38: 17:6426615-6426615
23 AIPL1 NM_014336.5(AIPL1):c.1008_1009AG[1] (p.Glu337fs) Microsatellite Pathogenic 5566 rs62637016 GRCh37: 17:6328924-6328925
GRCh38: 17:6425604-6425605
24 AIPL1 NM_014336.5(AIPL1):c.773G>C (p.Arg258Pro) SNV Likely pathogenic 916626 GRCh37: 17:6329946-6329946
GRCh38: 17:6426626-6426626
25 AIPL1 NM_014336.5(AIPL1):c.294del (p.Ile99fs) Deletion Likely pathogenic 638356 rs1597331616 GRCh37: 17:6331809-6331809
GRCh38: 17:6428489-6428489
26 AIPL1 NM_014336.5(AIPL1):c.98T>C (p.Val33Ala) SNV Conflicting interpretations of pathogenicity 707596 rs16955859 GRCh37: 17:6337417-6337417
GRCh38: 17:6434097-6434097
27 AIPL1 NM_014336.5(AIPL1):c.33G>C (p.Gly11=) SNV Conflicting interpretations of pathogenicity 771281 rs369223841 GRCh37: 17:6338392-6338392
GRCh38: 17:6435072-6435072
28 AIPL1 NM_014336.5(AIPL1):c.234C>T (p.Ser78=) SNV Conflicting interpretations of pathogenicity 99791 rs62635774 GRCh37: 17:6337281-6337281
GRCh38: 17:6433961-6433961
29 AIPL1 NM_014336.5(AIPL1):c.97-9G>A SNV Conflicting interpretations of pathogenicity 99808 rs140124986 GRCh37: 17:6337427-6337427
GRCh38: 17:6434107-6434107
30 AIPL1 NM_014336.5(AIPL1):c.267C>T (p.Cys89=) SNV Conflicting interpretations of pathogenicity 95582 rs62653020 GRCh37: 17:6337248-6337248
GRCh38: 17:6433928-6433928
31 AIPL1 NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) Deletion Conflicting interpretations of pathogenicity 5568 rs281865195 GRCh37: 17:6328871-6328882
GRCh38: 17:6425551-6425562
32 AIPL1 NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu) SNV Conflicting interpretations of pathogenicity 65712 rs62637015 GRCh37: 17:6329030-6329030
GRCh38: 17:6425710-6425710
33 AIPL1 NM_014336.5(AIPL1):c.401A>T (p.Tyr134Phe) SNV Conflicting interpretations of pathogenicity 196465 rs16955851 GRCh37: 17:6331702-6331702
GRCh38: 17:6428382-6428382
34 AIPL1 NM_014336.5(AIPL1):c.780C>T (p.His260=) SNV Conflicting interpretations of pathogenicity 324613 rs145304845 GRCh37: 17:6329939-6329939
GRCh38: 17:6426619-6426619
35 AIPL1 NM_014336.5(AIPL1):c.737A>C (p.Tyr246Ser) SNV Conflicting interpretations of pathogenicity 324614 rs138585919 GRCh37: 17:6329982-6329982
GRCh38: 17:6426662-6426662
36 AIPL1 NM_014336.5(AIPL1):c.765T>C (p.Asp255=) SNV Conflicting interpretations of pathogenicity 99806 rs62637018 GRCh37: 17:6329954-6329954
GRCh38: 17:6426634-6426634
37 AIPL1 NM_014336.5(AIPL1):c.1006G>A (p.Ala336Thr) SNV Conflicting interpretations of pathogenicity 166665 rs143092701 GRCh37: 17:6328929-6328929
GRCh38: 17:6425609-6425609
38 AIPL1 NM_014336.5(AIPL1):c.244C>T (p.His82Tyr) SNV Uncertain significance 95581 rs144822294 GRCh37: 17:6337271-6337271
GRCh38: 17:6433951-6433951
39 AIPL1 NM_014336.5(AIPL1):c.131A>T (p.Glu44Val) SNV Uncertain significance 1035468 GRCh37: 17:6337384-6337384
GRCh38: 17:6434064-6434064
40 AIPL1 NM_014336.5(AIPL1):c.817G>T (p.Ala273Ser) SNV Uncertain significance 1038458 GRCh37: 17:6329118-6329118
GRCh38: 17:6425798-6425798
41 AIPL1 NM_014336.5(AIPL1):c.203A>G (p.Lys68Arg) SNV Uncertain significance 1040845 GRCh37: 17:6337312-6337312
GRCh38: 17:6433992-6433992
42 AIPL1 NM_014336.5(AIPL1):c.246C>G (p.His82Gln) SNV Uncertain significance 1045372 GRCh37: 17:6337269-6337269
GRCh38: 17:6433949-6433949
43 AIPL1 NM_014336.5(AIPL1):c.796G>T (p.Ala266Ser) SNV Uncertain significance 388828 rs200939019 GRCh37: 17:6329139-6329139
GRCh38: 17:6425819-6425819
44 AIPL1 NM_014336.5(AIPL1):c.323C>T (p.Ala108Val) SNV Uncertain significance 846465 GRCh37: 17:6331780-6331780
GRCh38: 17:6428460-6428460
45 AIPL1 NM_014336.5(AIPL1):c.1030G>C (p.Ala344Pro) SNV Uncertain significance 846931 GRCh37: 17:6328905-6328905
GRCh38: 17:6425585-6425585
46 AIPL1 NM_014336.5(AIPL1):c.1090G>T (p.Ala364Ser) SNV Uncertain significance 291000 rs201875142 GRCh37: 17:6328845-6328845
GRCh38: 17:6425525-6425525
47 AIPL1 NM_014336.5(AIPL1):c.970C>A (p.Arg324=) SNV Uncertain significance 890026 GRCh37: 17:6328965-6328965
GRCh38: 17:6425645-6425645
48 AIPL1 NM_014336.5(AIPL1):c.158G>A (p.Arg53Gln) SNV Uncertain significance 960452 GRCh37: 17:6337357-6337357
GRCh38: 17:6434037-6434037
49 AIPL1 NM_014336.5(AIPL1):c.304C>G (p.Arg102Gly) SNV Uncertain significance 962280 GRCh37: 17:6331799-6331799
GRCh38: 17:6428479-6428479
50 AIPL1 NM_014336.5(AIPL1):c.570G>T (p.Lys190Asn) SNV Uncertain significance 968968 GRCh37: 17:6330273-6330273
GRCh38: 17:6426953-6426953

UniProtKB/Swiss-Prot genetic disease variations for Leber Congenital Amaurosis 4:

72
# Symbol AA change Variation ID SNP ID
1 AIPL1 p.Cys239Arg VAR_010139 rs62637012
2 AIPL1 p.Arg270His VAR_067165

Expression for Leber Congenital Amaurosis 4

Search GEO for disease gene expression data for Leber Congenital Amaurosis 4.

Pathways for Leber Congenital Amaurosis 4

GO Terms for Leber Congenital Amaurosis 4

Cellular components related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.86 TULP1 SPATA7 RPGRIP1 RD3 LCA5 GUCY2D
2 cilium GO:0005929 9.72 TULP1 RPGRIP1 LCA5 IQCB1 CEP290
3 ciliary basal body GO:0036064 9.63 SPATA7 LCA5 CEP290
4 photoreceptor inner segment GO:0001917 9.55 TULP1 RDH12 RD3 CRB1 AIPL1
5 axoneme GO:0005930 9.54 SPATA7 RPGRIP1 LCA5
6 photoreceptor disc membrane GO:0097381 9.43 PDE6A GUCY2D
7 photoreceptor outer segment membrane GO:0042622 9.4 PDE6A GUCY2D
8 photoreceptor connecting cilium GO:0032391 9.35 SPATA7 RPGRIP1 LCA5 IQCB1 CEP290
9 photoreceptor outer segment GO:0001750 9.1 TULP1 SPATA7 RD3 IQCB1 GUCY2D CRB1

Biological processes related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 retina development in camera-type eye GO:0060041 9.73 TULP1 RPGRIP1 RPE65 RD3 PDE6A CRB1
2 response to stimulus GO:0050896 9.73 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3
3 retinoid metabolic process GO:0001523 9.69 RPE65 RDH12 LRAT
4 retinol metabolic process GO:0042572 9.63 RPE65 RDH12 LRAT
5 photoreceptor cell maintenance GO:0045494 9.63 TULP1 SPATA7 RDH12 LCA5 IQCB1 CRB1
6 eye photoreceptor cell development GO:0042462 9.62 TULP1 RPGRIP1 CRB1 CEP290
7 retina homeostasis GO:0001895 9.61 TULP1 RPE65 AIPL1
8 regulation of rhodopsin mediated signaling pathway GO:0022400 9.58 PDE6A GUCY2D AIPL1
9 retina morphogenesis in camera-type eye GO:0060042 9.54 RPE65 CRB1
10 detection of light stimulus involved in visual perception GO:0050908 9.54 TULP1 RPE65 CRB1
11 phototransduction, visible light GO:0007603 9.52 PDE6C AIPL1
12 vitamin A metabolic process GO:0006776 9.49 RPE65 LRAT
13 protein localization to photoreceptor outer segment GO:1903546 9.48 TULP1 SPATA7
14 visual perception GO:0007601 9.44 TULP1 SPATA7 RPGRIP1 RPE65 RDH12 RD3

Molecular functions related to Leber Congenital Amaurosis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.89 TULP1 SPATA7 RPGRIP1 RDH12 RD3 PDE6C
2 3',5'-cyclic-nucleotide phosphodiesterase activity GO:0004114 9.16 PDE6C PDE6A
3 3',5'-cyclic-GMP phosphodiesterase activity GO:0047555 8.62 PDE6C PDE6A

Sources for Leber Congenital Amaurosis 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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