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KTCN1
MCID: KRT029
MIFTS: 35

Keratoconus 1 (KTCN1)

Categories: Eye diseases, Genetic diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Keratoconus 1

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MalaCards integrated aliases for Keratoconus 1:

Name: Keratoconus 1 56 73 29 13 6 71
Ktcn1 56 73
Keratoconus, Type 1 39

Characteristics:

OMIM:

56
Miscellaneous:
young adult onset
precipitation by pregnancy

Inheritance:
autosomal dominant


HPO:

31
keratoconus 1:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course young adult onset


Classifications:

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


External Ids:

OMIM 56 148300
OMIM Phenotypic Series 56 PS148300
MedGen 41 C1835677
SNOMED-CT via HPO 68 263681008 65636009 82649003
UMLS 71 C1835677
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Summaries for Keratoconus 1

About this section
OMIM : 56 Keratoconus, the most common corneal dystrophy, is a bilateral, noninflammatory progressive corneal ectasia. Clinically, the cornea becomes progressively thin and conical, resulting in myopia, irregular astigmatism, and corneal scarring. The disease usually arises in the teenage years, eventually stabilizing in the third and fourth decades. The incidence of keratoconus is 1 in 2,000 in the general population; it occurs with no ethnic or gender preponderance, and causes significant visual impairment in young adults. No specific treatment exists except to replace the corneal tissue by surgery (corneal transplantation) when visual acuity can no longer be corrected by contact lenses (summary by Dash et al., 2006). Ihalainen (1986) reviewed various conditions with which keratoconus is at times associated. Keratoconus is frequent in cases of amaurosis congenita of Leber (204000). (148300)

MalaCards based summary : Keratoconus 1, also known as ktcn1, is related to keratoconus 5 and keratoconus 6. An important gene associated with Keratoconus 1 is VSX1 (Visual System Homeobox 1), and among its related pathways/superpathways is Shigellosis. The drugs Folic acid and Riboflavin have been mentioned in the context of this disorder. Affiliated tissues include eye, and related phenotypes are keratoconus and astigmatism

UniProtKB/Swiss-Prot : 73 Keratoconus 1: Frequent corneal dystrophy with an incidence that varies from 50 to 230 per 100'000. The cornea assumes a conical shape as a result of a progressive non-inflammatory thinning of the corneal stroma. Keratoconus is most often an isolated sporadic condition with cases of autosomal dominant and autosomal recessive transmission.

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Related Diseases for Keratoconus 1

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Diseases in the Keratoconus family:

Keratoconus 1 Keratoconus 3
Keratoconus 2 Keratoconus 4
Keratoconus 5 Keratoconus 6
Keratoconus 8 Keratoconus 7
Keratoconus 9

Diseases related to Keratoconus 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 keratoconus 5 11.2
2 keratoconus 6 11.2
3 keratoconus 8 11.2
4 keratoconus 7 11.2
5 irregular astigmatism 10.0 ZNF469 VSX1
6 corneal ectasia 10.0 ZNF469 VSX1
7 brittle cornea syndrome 2 10.0 ZNF469 VSX1
8 fuchs' endothelial dystrophy 10.0 ZNF469 VSX1
9 corneal disease 9.9 ZNF469 VSX1
10 brittle bone disorder 9.9 ZNF469 VSX1
11 corneal dystrophy, posterior polymorphous, 1 9.8 ZNF469 VSX1
12 corneal endothelial dystrophy 9.7 ZNF469 VSX1
13 keratoconus 8.3 ZNF469 VSX1 SKP1 PROB1 IL17B HKDC1

Graphical network of the top 20 diseases related to Keratoconus 1:



Diseases related to Keratoconus 1
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Symptoms & Phenotypes for Keratoconus 1

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Human phenotypes related to Keratoconus 1:

31
# Description HPO Frequency HPO Source Accession
1 keratoconus 31 HP:0000563
2 astigmatism 31 HP:0000483

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
keratoconus
astigmatism
predictors of acute corneal hydrops
increased epithelial thickening
stromal thinning at the cone
more

Clinical features from OMIM:

148300
Sources

Drugs & Therapeutics for Keratoconus 1

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Drugs for Keratoconus 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Folic acid Approved, Nutraceutical, Vet_approved Phase 3 59-30-3 6037
2
Riboflavin Approved, Investigational, Nutraceutical, Vet_approved Phase 3 83-88-5 493570
3 Trace Elements Phase 3
4 Vitamins Phase 3
5 Micronutrients Phase 3
6 Vitamin B Complex Phase 3
7 Nutrients Phase 3
8 Dermatologic Agents Phase 3
9 Vitamin B2 Phase 3
10 Folate Phase 3
11 Vitamin B9 Phase 3
12 Photosensitizing Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Comparison of Corneal Collagen Cross-Linking Performed With "Epi-ON" Versus "Epi-OFF" Techniques in Eyes With Keratoconus and Other Corneal Ectatic Disorders Not yet recruiting NCT03858036 Phase 3 Ricrolin+

Search NIH Clinical Center for Keratoconus 1

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Genetic Tests for Keratoconus 1

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Genetic tests related to Keratoconus 1:

# Genetic test Affiliating Genes
1 Keratoconus 1 29 VSX1
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Anatomical Context for Keratoconus 1

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MalaCards organs/tissues related to Keratoconus 1:

40
Eye
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Publications for Keratoconus 1

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Articles related to Keratoconus 1:

(show top 50) (show all 55)
# Title Authors PMID Year
1
Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus. 56 6
21976959 2011
2
Three VSX1 gene mutations, L159M, R166W, and H244R, are not associated with keratoconus. 56 6
18216574 2008
3
VSX1 mutational analysis in a series of Italian patients affected by keratoconus: detection of a novel mutation. 56 6
15623752 2005
4
VSX1: a gene for posterior polymorphous dystrophy and keratoconus. 56 6
11978762 2002
5
Anatomic Predictive Factors of Acute Corneal Hydrops in Keratoconus: An Optical Coherence Tomography Study. 56
26045363 2015
6
Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity. 56
25593510 2015
7
Analysis of the SOD1 Gene in Keratoconus Patients from Saudi Arabia. 56
24547927 2015
8
Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus. 56
24895405 2014
9
Mutational screening of VSX1 in keratoconus patients from the European population. 56
19763142 2010
10
Genetics and clinical characteristics of keratoconus. 56
20664914 2010
11
Changes in the balance of the tissue inhibitor of matrix metalloproteinases (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus. 56
17449031 2007
12
SOD1: a candidate gene for keratoconus. 56
16877401 2006
13
Fine mapping of the keratoconus with cataract locus on chromosome 15q and candidate gene analysis. 56
16735990 2006
14
Accumulation of mitochondrial DNA damage in keratoconus corneas. 56
15790887 2005
15
Inflammatory molecules in the tears of patients with keratoconus. 56
15808258 2005
16
Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. 56
15728537 2005
17
Longitudinal study of the normal eyes in unilateral keratoconus patients. 56
15019316 2004
18
Tear function and ocular surface changes in keratoconus. 56
12799234 2003
19
Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays. 56
12766045 2003
20
Preliminary findings in corneal allograft rejection in patients with keratoconus. 56
12654360 2003
21
Identity-by-descent approach to gene localisation in eight individuals affected by keratoconus from north-west Tasmania, Australia. 56
12073017 2002
22
Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region. 56
11773012 2002
23
Corneal ectasia after laser-assisted in situ keratomileusis. 56
11709027 2001
24
Genetic epidemiological study of keratoconus: evidence for major gene determination. 56
10951465 2000
25
Health care concerns and guidelines for adults with Down syndrome. 56
10559765 1999
26
A 48-year clinical and epidemiologic study of keratoconus. 56
3513592 1986
27
Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. 56
3019073 1986
28
The ocular features of Down's syndrome. 56
3160242 1985
29
[Genetic aspects of keratoconus (author's transl)]. 56
894997 1977
30
Dominantly inherited keratoconus. 56
5387413 1969
31
THE SIGNIFICANCE OF HEREDITY IN OPHTHALMOLOGY. PRELIMINARY SURVEY OF HEREDITARY EYE DISEASES IN TASMANIA. 56
18169511 1938
32
Regenerative Surgery of the Corneal Stroma for Advanced Keratoconus: 1-Year Outcomes. 61
30772348 2019
33
Transepithelial accelerated corneal collagen cross-linking with higher oxygen availability for keratoconus: 1-year results. 61
29116549 2018
34
United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment. 61
28495149 2017
35
Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. 61
27899371 2017
36
Topographic outcomes after corneal collagen crosslinking in progressive keratoconus: 1-year follow-up. 61
28591281 2017
37
Keratoconus in Inflammatory Bowel Disease Patients: A Cross-sectional Study. 61
26351387 2015
38
Changes in corneal topography and biomechanical properties after collagen cross linking for keratoconus: 1-year results. 61
25949080 2015
39
Corneal transparency after cross-linking for keratoconus: 1-year follow-up. 61
23347372 2012
40
Safety and efficacy of simultaneous corneal collagen cross-linking with topography-guided PRK in managing low-grade keratoconus: 1-year follow-up. 61
22443804 2012
41
Fluid-filled scleral contact lenses in vernal keratoconjunctivitis. 61
22367220 2012
42
[Corneal cross-linking with hypo-osmolar riboflavin solution for keratoconus with thin corneas]. 61
21858523 2011
43
[Corneal cross-linking--modern method of keratoconus treatment]. 61
21416705 2010
44
Corneal volume, pachymetry, and correlation of anterior and posterior corneal shape in subclinical and different stages of clinical keratoconus. 61
20457375 2010
45
Keratoconus detection using corneal topography. 61
19848378 2009
46
The therapeutic and optical application of a rigid gas permeable semi-limbal diameter contact lens. 61
19442562 2009
47
[A preliminary report of epikeratophakia combined with two-stage photorefractive keratectomy in the treatment of keratoconus]. 61
17605905 2007
48
Angle closure in highly myopic eyes. 61
16427698 2006
49
Prevalence and causes of blindness and visual impairment among school children in south-western Nigeria. 61
17200795 2005
50
Repeat keratoplasty for correction of high or irregular postkeratoplasty astigmatism in clear corneal grafts. 61
15860287 2005
Sources

Variations for Keratoconus 1

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ClinVar genetic disease variations for Keratoconus 1:

6 (show all 40) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VSX1 NM_014588.5(VSX1):c.496C>T (p.Arg166Trp)SNV Pathogenic 5247 rs74315432 20:25060079-25060079 20:25079443-25079443
2 ZNF469 NM_001367624.1(ZNF469):c.11185G>A (p.Gly3729Ser)SNV Pathogenic 126918 rs273585629 16:88505063-88505063 16:88438655-88438655
3 ZNF469 NM_001367624.1(ZNF469):c.11699C>T (p.Pro3900Leu)SNV Pathogenic 126919 rs273585630 16:88505577-88505577 16:88439169-88439169
4 ZNF469 NM_001367624.1(ZNF469):c.290C>T (p.Pro97Leu)SNV Pathogenic 126923 rs273585617 16:88494168-88494168 16:88427760-88427760
5 ZNF469 NM_001367624.1(ZNF469):c.3119A>C (p.Lys1040Thr)SNV Pathogenic 126924 rs273585619 16:88496997-88496997 16:88430589-88430589
6 ZNF469 NM_001367624.1(ZNF469):c.4447G>T (p.Ala1483Ser)SNV Pathogenic 126925 rs273585620 16:88498325-88498325 16:88431917-88431917
7 ZNF469 NM_001367624.1(ZNF469):c.6179C>A (p.Ser2060Tyr)SNV Pathogenic 126928 rs273585623 16:88500057-88500057 16:88433649-88433649
8 ZNF469 NM_001367624.1(ZNF469):c.6809C>A (p.Ser2270Tyr)SNV Pathogenic 126929 rs273585624 16:88500687-88500687 16:88434279-88434279
9 ZNF469 NM_001367624.1(ZNF469):c.77G>C (p.Ser26Thr)SNV Pathogenic 126931 rs273585616 16:88493955-88493955 16:88427547-88427547
10 ZNF469 NM_001367624.1(ZNF469):c.8996G>T (p.Gly2999Val)SNV Pathogenic 126932 rs273585625 16:88502874-88502874 16:88436466-88436466
11 ZNF469 NM_001367624.1(ZNF469):c.2063C>A (p.Thr688Asn)SNV Pathogenic 126938 rs281865146 16:88495941-88495941 16:88429533-88429533
12 ZNF469 NM_001367624.1(ZNF469):c.2699C>G (p.Pro900Arg)SNV Pathogenic 126939 rs273585618 16:88496577-88496577 16:88430169-88430169
13 ZNF469 NM_001127464.2(ZNF469):c.2904_2909delGTCGGG (p.Ser969_Gly970del)short repeat Pathogenic 126940 rs281865147 16:88496782-88496787 16:88430374-88430379
14 ZNF469 NM_001367624.1(ZNF469):c.337G>A (p.Glu113Lys)SNV Pathogenic 126942 rs281865144 16:88494215-88494215 16:88427807-88427807
15 ZNF469 NM_001367624.1(ZNF469):c.5681A>T (p.Gln1894Leu)SNV Pathogenic 126944 rs281865150 16:88499559-88499559 16:88433151-88433151
16 ZNF469 NM_001367624.1(ZNF469):c.7931G>A (p.Arg2644Gln)SNV Likely pathogenic 126946 rs281865152 16:88501809-88501809 16:88435401-88435401
17 ZNF469 NM_001367624.1(ZNF469):c.5144G>A (p.Arg1715Lys)SNV Likely pathogenic 126943 rs281865149 16:88499022-88499022 16:88432614-88432614
18 ZNF469 NM_001367624.1(ZNF469):c.99G>A (p.Pro33=)SNV Likely pathogenic 126936 rs273585631 16:88493977-88493977 16:88427569-88427569
19 ZNF469 NM_001367624.1(ZNF469):c.720G>A (p.Glu240=)SNV Likely pathogenic 126930 rs273585632 16:88494598-88494598 16:88428190-88428190
20 ZNF469 NM_001367624.1(ZNF469):c.10927C>T (p.Leu3643=)SNV Likely pathogenic 126917 rs273585637 16:88504805-88504805 16:88438397-88438397
21 ZNF469 NM_001367624.1(ZNF469):c.2478G>T (p.Pro826=)SNV Likely pathogenic 126920 rs273585634 16:88496356-88496356 16:88429948-88429948
22 ZNF469 NM_001367624.1(ZNF469):c.1020C>T (p.Gly340=)SNV Conflicting interpretations of pathogenicity 126915 rs273585633 16:88494898-88494898 16:88428490-88428490
23 ZNF469 NM_001367624.1(ZNF469):c.2699C>T (p.Pro900Leu)SNV Conflicting interpretations of pathogenicity 126922 rs273585618 16:88496577-88496577 16:88430169-88430169
24 VSX1 NM_014588.5(VSX1):c.475T>A (p.Leu159Met)SNV Uncertain significance 5249 rs74315434 20:25060100-25060100 20:25079464-25079464
25 ZNF469 NM_001367624.1(ZNF469):c.7831G>A (p.Glu2611Lys)SNV Uncertain significance 126945 rs281865151 16:88501709-88501709 16:88435301-88435301
26 ZNF469 NM_001367624.1(ZNF469):c.9131C>T (p.Thr3044Met)SNV Uncertain significance 126933 rs273585626 16:88503009-88503009 16:88436601-88436601
27 SKP1 NM_006930.3(SKP1):c.475T>G (p.Cys159Gly)SNV Uncertain significance 225700 rs1114167278 5:133494127-133494127 5:134158436-134158436
28 PROB1 NM_001161546.2(PROB1):c.671G>A (p.Gly224Asp)SNV Uncertain significance 225701 rs1114167279 5:138730100-138730100 5:139394411-139394411
29 IL17B NM_014443.3(IL17B):c.527G>A (p.Cys176Tyr)SNV Uncertain significance 225702 rs201298520 5:148753948-148753948 5:149374385-149374385
30 HKDC1 NM_025130.4(HKDC1):c.850G>A (p.Gly284Ser)SNV Uncertain significance 225703 rs202105296 10:71003096-71003096 10:69243340-69243340
31 ZNF469 NM_001367624.1(ZNF469):c.9919A>G (p.Thr3307Ala)SNV Uncertain significance 126935 rs273585627 16:88503797-88503797 16:88437389-88437389
32 ZNF469 NM_001367624.1(ZNF469):c.9555C>G (p.Ala3185=)SNV Likely benign 126934 rs273585636 16:88503433-88503433 16:88437025-88437025
33 ZNF469 NM_001127464.2(ZNF469):c.9011_9025delTTCCCGGGAACACCC (p.Leu3004_Thr3008del)deletion Likely benign 126947 rs281865162 16:88502973-88502987 16:88436565-88436579
34 VSX1 NM_014588.5(VSX1):c.50T>C (p.Leu17Pro)SNV Likely benign 5251 rs74315436 20:25062683-25062683 20:25082047-25082047
35 ZNF469 NM_001367624.1(ZNF469):c.10573G>A (p.Glu3525Lys)SNV Benign 126916 rs273585628 16:88504451-88504451 16:88438043-88438043
36 ZNF469 NM_001367624.1(ZNF469):c.2643C>G (p.Ser881=)SNV Benign 126921 rs273585635 16:88496521-88496521 16:88430113-88430113
37 ZNF469 NM_001367624.1(ZNF469):c.4910G>C (p.Arg1637Pro)SNV Benign 126926 rs273585621 16:88498788-88498788 16:88432380-88432380
38 ZNF469 NM_001367624.1(ZNF469):c.6091G>A (p.Glu2031Lys)SNV Benign 126927 rs273585622 16:88499969-88499969 16:88433561-88433561
39 ZNF469 NM_001367624.1(ZNF469):c.1627G>A (p.Gly543Ser)SNV Benign 126937 rs281865145 16:88495505-88495505 16:88429097-88429097
40 ZNF469 NM_001367624.1(ZNF469):c.3320G>A (p.Arg1107Gln)SNV Benign 126941 rs281865148 16:88497198-88497198 16:88430790-88430790

UniProtKB/Swiss-Prot genetic disease variations for Keratoconus 1:

73
# Symbol AA change Variation ID SNP ID
1 VSX1 p.Arg166Trp VAR_014246 rs74315432
2 VSX1 p.Gln175His VAR_063100 rs771561481
3 VSX1 p.Leu17Pro VAR_066670 rs74315436

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Expression for Keratoconus 1

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Search GEO for disease gene expression data for Keratoconus 1.
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Pathways for Keratoconus 1

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Pathways related to Keratoconus 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Shigellosis 36
11 SKP1 HKDC1
Sources

GO Terms for Keratoconus 1

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Sources

Sources for Keratoconus 1

About this section
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
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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