COD3
MCID: CND011
MIFTS: 38

Cone Dystrophy 3 (COD3)

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

Aliases & Classifications for Cone Dystrophy 3

MalaCards integrated aliases for Cone Dystrophy 3:

Name: Cone Dystrophy 3 56 73 29 6 43 71
Cone-Rod Dystrophy 14 56 12
Cone Dystrophy-3 56 13
Cod3 56 73
Dystrophy, Cone, Type 3 39
Retinal Cone Dystrophy 56

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
intrafamilial phenotypic variability
onset in the first two decades of life


HPO:

31
cone dystrophy 3:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080314
OMIM 56 602093
OMIM Phenotypic Series 56 PS120970
MedGen 41 C1865869
UMLS 71 C1838190 C1865869

Summaries for Cone Dystrophy 3

OMIM : 56 Progressive cone dystrophy usually presents in childhood or early adult life, with many patients developing rod photoreceptor involvement in later life, thereby leading to considerable overlap between progressive cone dystrophy and cone-rod dystrophy. Both progressive cone dystrophy and cone-rod dystrophy have been associated with mutation in the GUCA1A gene (Michaelides et al., 2006). Intrafamilial variability in GUCA1A-associated macular disease ranges from mild photoreceptor degeneration to central areolar choroidal dystrophy (CACD), a form of retinal degeneration that primarily involves the macula and is characterized by a well-defined atrophic region of retinal pigment epithelium and choriocapillaris in the latest stage (Chen et al., 2017). (602093)

MalaCards based summary : Cone Dystrophy 3, also known as cone-rod dystrophy 14, is related to retinal cone dystrophy 3a and cone-rod dystrophy 6, and has symptoms including photophobia An important gene associated with Cone Dystrophy 3 is GUCA1A (Guanylate Cyclase Activator 1A), and among its related pathways/superpathways are Phototransduction and Visual Cycle in Retinal Rods. Affiliated tissues include retina, and related phenotypes are macular atrophy and photophobia

Disease Ontology : 12 A cone-rod dystrophy that is characterized by deterioration of the cone in childhood or early adult life and progressive deterioration of the rod photoreceptor cells in later life that has material basis in mutation in GUCA1A on chromosome 6p21.1.

UniProtKB/Swiss-Prot : 73 Cone dystrophy 3: An autosomal dominant cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.

Related Diseases for Cone Dystrophy 3

Diseases in the Cone Dystrophy family:

Cone Dystrophy 3 Cone Dystrophy 4

Diseases related to Cone Dystrophy 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 retinal cone dystrophy 3a 31.5 PDE6H KCNV2
2 cone-rod dystrophy 6 30.6 PDE6H KCNV2 GUCA1B GUCA1A CACNA2D4
3 cone dystrophy 30.1 PDE6H KCNV2 GUCA1B GUCA1A CACNA2D4
4 retinal cone dystrophy 4 12.7
5 retinal cone dystrophy 3b 12.5
6 retinal cone dystrophy 1 12.5
7 partial central choroid dystrophy 10.1 GUCA1B GUCA1A
8 hereditary choroidal atrophy 10.0 GUCA1B GUCA1A
9 leber congenital amaurosis 1 10.0 GUCA1B GUCA1A
10 leber congenital amaurosis 12 10.0 GUCA1B GUCA1A
11 bardet-biedl syndrome 4 10.0 GUCA1B GUCA1A
12 tetralogy of fallot 10.0
13 vesicoureteral reflux 1 10.0
14 ataxia and polyneuropathy, adult-onset 10.0
15 light fixation seizure syndrome 10.0
16 autosomal recessive disease 10.0
17 visual epilepsy 10.0
18 chromosome 6q deletion 10.0
19 seizure disorder 10.0
20 multiple congenital anomalies/dysmorphic syndrome-intellectual disability 10.0
21 retinitis pigmentosa 7 9.9 GUCA1B GUCA1A
22 choroidal dystrophy, central areolar, 1 9.9 GUCA1B GUCA1A
23 scotoma 9.9 KCNV2 GUCA1A
24 prolonged electroretinal response suppression 9.9 KCNV2 GUCA1A
25 nephronophthisis 4 9.8 KCNV2 GUCA1B
26 congenital stationary night blindness 9.7 GUCA1B GUCA1A CACNA2D4
27 stargardt disease 9.7 KCNV2 GUCA1A
28 night blindness 9.6 PDE6H KCNV2
29 achromatopsia 4 9.6 PDE6H KCNV2
30 eye degenerative disease 9.6 GUCA1B GUCA1A
31 color blindness 9.5 PDE6H KCNV2
32 pathologic nystagmus 9.4 PDE6H KCNV2
33 cone-rod dystrophy 2 9.3 PDE6H GUCA1A CACNA2D4
34 achromatopsia 9.1 PDE6H KCNV2 GUCA1A CACNA2D4
35 leber plus disease 9.0 PDE6H KCNV2 GUCA1B GUCA1A
36 fundus dystrophy 8.7 PDE6H KCNV2 GUCA1B GUCA1A CACNA2D4
37 retinitis pigmentosa 8.6 PDE6H KCNV2 GUCA1B GUCA1A CACNA2D4

Graphical network of the top 20 diseases related to Cone Dystrophy 3:



Diseases related to Cone Dystrophy 3

Symptoms & Phenotypes for Cone Dystrophy 3

Human phenotypes related to Cone Dystrophy 3:

31
# Description HPO Frequency HPO Source Accession
1 macular atrophy 31 occasional (7.5%) HP:0007401
2 photophobia 31 HP:0000613
3 progressive visual loss 31 HP:0000529
4 reduced visual acuity 31 HP:0007663
5 cone/cone-rod dystrophy 31 HP:0000548

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
photophobia
central scotomas
decreased central vision
progressive vision loss
decreased color vision
more

Clinical features from OMIM:

602093

UMLS symptoms related to Cone Dystrophy 3:


photophobia

MGI Mouse Phenotypes related to Cone Dystrophy 3:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 vision/eye MP:0005391 9.02 CACNA2D4 GUCA1A GUCA1B KCNV2 PDE6H

Drugs & Therapeutics for Cone Dystrophy 3

Search Clinical Trials , NIH Clinical Center for Cone Dystrophy 3

Cochrane evidence based reviews: cone dystrophy 3

Genetic Tests for Cone Dystrophy 3

Genetic tests related to Cone Dystrophy 3:

# Genetic test Affiliating Genes
1 Cone Dystrophy 3 29 GUCA1A

Anatomical Context for Cone Dystrophy 3

MalaCards organs/tissues related to Cone Dystrophy 3:

40
Retina

Publications for Cone Dystrophy 3

Articles related to Cone Dystrophy 3:

(show all 18)
# Title Authors PMID Year
1
GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity. 6 56
28125083 2017
2
Novel GUCA1A mutations suggesting possible mechanisms of pathogenesis in cone, cone-rod, and macular dystrophy patients. 56 6
24024198 2013
3
Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy. 56 6
15953638 2005
4
A novel GCAP1 missense mutation (L151F) in a large family with autosomal dominant cone-rod dystrophy (adCORD). 56 6
15790869 2005
5
Autosomal dominant cone dystrophy caused by a novel mutation in the GCAP1 gene (GUCA1A). 6 56
15735604 2005
6
A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. 6 56
9425234 1998
7
Two retinal dystrophy-associated missense mutations in GUCA1A with distinct molecular properties result in a similar aberrant regulation of the retinal guanylate cyclase. 6
26358777 2015
8
Cone rod dystrophies. 6
17270046 2007
9
Progressive cone and cone-rod dystrophies: phenotypes and underlying molecular genetic basis. 56
16644365 2006
10
Local cone and rod system function in progressive cone dystrophy. 56
12091439 2002
11
Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1. 6
11146732 2001
12
HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. 6
11006213 2000
13
Constitutive activation of photoreceptor guanylate cyclase by Y99C mutant of GCAP-1. Possible role in causing human autosomal dominant cone degeneration. 6
9651312 1998
14
GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy. 6
9702199 1998
15
Dominant cone-rod dystrophy: a mouse model generated by gene targeting of the GCAP1/Guca1a gene. 61
21464903 2011
16
Identification and functional consequences of a new mutation (E155G) in the gene for GCAP1 that causes autosomal dominant cone dystrophy. 61
11484154 2001
17
Analysis of peripherin/RDS gene for Japanese retinal dystrophies. 61
9690896 1998
18
Simultaneous foveal and parafoveal electroretinograms in hereditary degeneration of the central retina. 61
2791851 1989

Variations for Cone Dystrophy 3

ClinVar genetic disease variations for Cone Dystrophy 3:

6 (show top 50) (show all 60) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GUCA1A NM_000409.4(GUCA1A):c.359_360delinsTT (p.Arg120Leu)indel Pathogenic 453246 rs1554186441 6:42146547-42146548 6:42178809-42178810
2 GUCA1A NM_000409.5(GUCA1A):c.359G>T (p.Arg120Leu)SNV Pathogenic 802212 6:42146547-42146547 6:42178809-42178809
3 GUCA1A NM_000409.4(GUCA1A):c.451C>T (p.Leu151Phe)SNV Pathogenic 9152 rs121434631 6:42146986-42146986 6:42179248-42179248
4 GUCA1A NM_000409.4(GUCA1A):c.250C>T (p.Leu84Phe)SNV Pathogenic 225232 rs869320709 6:42146066-42146066 6:42178328-42178328
5 GUCA1A NM_000409.4(GUCA1A):c.320T>C (p.Ile107Thr)SNV Pathogenic 225233 rs869320710 6:42146136-42146136 6:42178398-42178398
6 GUCA1A NM_000409.4(GUCA1A):c.296A>G (p.Tyr99Cys)SNV Pathogenic 9150 rs104893967 6:42146112-42146112 6:42178374-42178374
7 GUCA1A NM_000409.4(GUCA1A):c.149C>T (p.Pro50Leu)SNV Conflicting interpretations of pathogenicity 9151 rs104893968 6:42141500-42141500 6:42173762-42173762
8 KCNV2 NM_133497.4(KCNV2):c.80G>A (p.Arg27His)SNV Conflicting interpretations of pathogenicity 143162 rs145731729 9:2717819-2717819 9:2717819-2717819
9 CACNA2D4 NM_172364.5(CACNA2D4):c.2120G>A (p.Arg707His)SNV Conflicting interpretations of pathogenicity 307853 rs76064926 12:1965210-1965210 12:1856044-1856044
10 GUCA1A , GUCA1B NM_000409.4(GUCA1A):c.*10C>ASNV Conflicting interpretations of pathogenicity 369542 rs367804008 6:42147151-42147151 6:42179413-42179413
11 PDE6H NM_006205.2(PDE6H):c.-102G>TSNV Uncertain significance 307779 rs533569725 12:15125960-15125960 12:14973026-14973026
12 CACNA2D4 NM_172364.5(CACNA2D4):c.3339G>A (p.Ser1113=)SNV Uncertain significance 307833 rs371916321 12:1902896-1902896 12:1793730-1793730
13 CACNA2D4 NM_172364.5(CACNA2D4):c.*425G>ASNV Uncertain significance 307824 rs886049120 12:1902396-1902396 12:1793230-1793230
14 CACNA2D4 NM_172364.5(CACNA2D4):c.684A>C (p.Glu228Asp)SNV Uncertain significance 307868 rs886049131 12:2016703-2016703 12:1907537-1907537
15 CACNA2D4 NM_172364.5(CACNA2D4):c.2714C>T (p.Ser905Phe)SNV Uncertain significance 307842 rs372942250 12:1919451-1919451 12:1810285-1810285
16 CACNA2D4 NM_172364.5(CACNA2D4):c.593T>A (p.Leu198Gln)SNV Uncertain significance 307869 rs200563551 12:2017097-2017097 12:1907931-1907931
17 GUCA1A NM_001370581.1(LOC114841037):c.219G>A (p.Pro73=)SNV Uncertain significance 356688 rs748633700 6:42130822-42130822 6:42163084-42163084
18 GUCA1A NM_001370581.1(LOC114841037):c.124C>A (p.His42Asn)SNV Uncertain significance 356687 rs886061391 6:42130727-42130727 6:42162989-42162989
19 GUCA1A NM_000409.4(GUCA1A):c.-242C>TSNV Uncertain significance 356689 rs531277306 6:42141110-42141110 6:42173372-42173372
20 GUCA1A NM_000409.4(GUCA1A):c.10G>A (p.Val4Met)SNV Uncertain significance 356692 rs200110820 6:42141361-42141361 6:42173623-42173623
21 GUCA1A NM_001370581.1(LOC114841037):c.-25T>CSNV Uncertain significance 356683 rs543150310 6:42123253-42123253 6:42155515-42155515
22 CACNA2D4 NM_172364.5(CACNA2D4):c.2868+4_2868+7deldeletion Uncertain significance 307840 rs760300917 12:1910202-1910205 12:1801036-1801039
23 GUCA1A NM_000409.4(GUCA1A):c.364A>G (p.Ile122Val)SNV Uncertain significance 167161 rs372323165 6:42146552-42146552 6:42178814-42178814
24 GUCA1A NM_000409.4(GUCA1A):c.142C>T (p.Leu48=)SNV Uncertain significance 167160 rs35969994 6:42141493-42141493 6:42173755-42173755
25 GUCA1A NM_000409.4(GUCA1A):c.*548C>TSNV Uncertain significance 356698 rs886061392 6:42147689-42147689 6:42179951-42179951
26 GUCA1A NM_001370581.1(LOC114841037):c.47G>T (p.Gly16Val)SNV Uncertain significance 356685 rs181327724 6:42123324-42123324 6:42155586-42155586
27 GUCA1A NM_000409.5(GUCA1A):c.313_318del (p.Gly105_Cys106del)deletion Uncertain significance 829997 6:42146128-42146133 6:42178390-42178395
28 GUCA1A NM_000409.5(GUCA1A):c.568G>C (p.Glu190Gln)SNV Uncertain significance 841640 6:42147103-42147103 6:42179365-42179365
29 GUCA1A NM_001370581.1(LOC114841037):c.39C>T (p.His13=)SNV Uncertain significance 906414 6:42123316-42123316 6:42155578-42155578
30 GUCA1A NM_001370581.1(LOC114841037):c.46G>A (p.Gly16Ser)SNV Uncertain significance 906415 6:42123323-42123323 6:42155585-42155585
31 GUCA1A NM_001370581.1(LOC114841037):c.99G>A (p.Pro33=)SNV Uncertain significance 907415 6:42130702-42130702 6:42162964-42162964
32 GUCA1A NM_000409.5(GUCA1A):c.*357A>GSNV Uncertain significance 912179 6:42147498-42147498 6:42179760-42179760
33 GUCA1A NM_000409.5(GUCA1A):c.*479C>GSNV Uncertain significance 908169 6:42147620-42147620 6:42179882-42179882
34 GUCA1A NM_001370581.1(LOC114841037):c.134G>A (p.Arg45Gln)SNV Uncertain significance 908106 6:42130737-42130737 6:42162999-42162999
35 GUCA1A NM_001370581.1(LOC114841037):c.140G>A (p.Arg47Gln)SNV Uncertain significance 910054 6:42130743-42130743 6:42163005-42163005
36 GUCA1A NM_000409.5(GUCA1A):c.-88G>ASNV Uncertain significance 910055 6:42141264-42141264 6:42173526-42173526
37 GUCA1A NM_000409.5(GUCA1A):c.551A>G (p.Gln184Arg)SNV Uncertain significance 910954 6:42147086-42147086 6:42179348-42179348
38 GUCA1A NM_000409.5(GUCA1A):c.*140G>CSNV Uncertain significance 912175 6:42147281-42147281 6:42179543-42179543
39 GUCA1A NM_000409.5(GUCA1A):c.*213G>ASNV Uncertain significance 912176 6:42147354-42147354 6:42179616-42179616
40 GUCA1A NM_000409.5(GUCA1A):c.*332T>CSNV Uncertain significance 912177 6:42147473-42147473 6:42179735-42179735
41 GUCA1A NM_000409.5(GUCA1A):c.*336C>TSNV Uncertain significance 912178 6:42147477-42147477 6:42179739-42179739
42 GUCA1A NM_000409.5(GUCA1A):c.*538T>GSNV Uncertain significance 908170 6:42147679-42147679 6:42179941-42179941
43 GUCA1A NM_000409.5(GUCA1A):c.201+11G>TSNV Uncertain significance 910953 6:42141563-42141563 6:42173825-42173825
44 GUCA1A , GUCA1B NM_000409.4(GUCA1A):c.*331A>GSNV Likely benign 356695 rs45553838 6:42147472-42147472 6:42179734-42179734
45 GUCA1A NM_000409.4(GUCA1A):c.*227C>ASNV Likely benign 356694 rs566678219 6:42147368-42147368 6:42179630-42179630
46 GUCA1A , GUCA1B NM_000409.4(GUCA1A):c.*76C>ASNV Likely benign 356693 rs76792280 6:42147217-42147217 6:42179479-42179479
47 GUCA1A , GUCA1B NM_000409.4(GUCA1A):c.*345G>ASNV Likely benign 356696 rs115636833 6:42147486-42147486 6:42179748-42179748
48 GUCA1A NM_000409.4(GUCA1A):c.*627T>ASNV Likely benign 356699 rs56285673 6:42147768-42147768 6:42180030-42180030
49 CACNA2D4 NM_172364.5(CACNA2D4):c.*1078deldeletion Likely benign 307815 rs3214264 12:1901743-1901743 12:1792577-1792577
50 GUCA1A , GUCA1B NM_000409.4(GUCA1A):c.*415C>TSNV Likely benign 369546 rs182201426 6:42147556-42147556 6:42179818-42179818

UniProtKB/Swiss-Prot genetic disease variations for Cone Dystrophy 3:

73
# Symbol AA change Variation ID SNP ID
1 GUCA1A p.Tyr99Cys VAR_001372 rs104893967
2 GUCA1A p.Pro50Leu VAR_010648 rs104893968
3 GUCA1A p.Glu155Gly VAR_012987
4 GUCA1A p.Glu89Lys VAR_060802
5 GUCA1A p.Asp100Glu VAR_060803
6 GUCA1A p.Leu151Phe VAR_060806 rs121434631
7 GUCA1A p.Gly159Val VAR_060807

Expression for Cone Dystrophy 3

Search GEO for disease gene expression data for Cone Dystrophy 3.

Pathways for Cone Dystrophy 3

Pathways related to Cone Dystrophy 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.99 PDE6H GUCA1B GUCA1A
2 10.93 GUCA1B GUCA1A

GO Terms for Cone Dystrophy 3

Cellular components related to Cone Dystrophy 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 photoreceptor outer segment GO:0001750 8.96 GUCA1B GUCA1A
2 photoreceptor disc membrane GO:0097381 8.62 GUCA1B GUCA1A

Biological processes related to Cone Dystrophy 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to stimulus GO:0050896 9.43 PDE6H GUCA1B GUCA1A
2 regulation of ion transmembrane transport GO:0034765 9.32 KCNV2 CACNA2D4
3 regulation of rhodopsin mediated signaling pathway GO:0022400 9.16 GUCA1B GUCA1A
4 visual perception GO:0007601 9.13 PDE6H GUCA1B GUCA1A
5 positive regulation of guanylate cyclase activity GO:0031284 8.62 GUCA1B GUCA1A

Molecular functions related to Cone Dystrophy 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 voltage-gated ion channel activity GO:0005244 9.16 KCNV2 CACNA2D4
2 calcium sensitive guanylate cyclase activator activity GO:0008048 8.96 GUCA1B GUCA1A
3 guanylate cyclase regulator activity GO:0030249 8.62 GUCA1B GUCA1A

Sources for Cone Dystrophy 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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