MKS4
MCID: MCK033
MIFTS: 39

Meckel Syndrome, Type 4 (MKS4)

Categories: Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Meckel Syndrome, Type 4

MalaCards integrated aliases for Meckel Syndrome, Type 4:

Name: Meckel Syndrome, Type 4 58 41 74
Meckel Syndrome 4 58 12 76 13 15
Mks4 58 12 76
Meckel-Gruber Syndrome, Type 4 58 12
Meckel Syndrome Type 4 30 6

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
lethal in utero or perinatal lethal


HPO:

33
meckel syndrome, type 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Meckel Syndrome, Type 4

OMIM : 58 Meckel syndrome is an autosomal recessive pre- or perinatal lethal disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Baala et al., 2007). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000). (611134)

MalaCards based summary : Meckel Syndrome, Type 4, also known as meckel syndrome 4, is related to joubert syndrome 5 and joubert syndrome 6. An important gene associated with Meckel Syndrome, Type 4 is CEP290 (Centrosomal Protein 290). The drug cysteine has been mentioned in the context of this disorder. Affiliated tissues include bone, kidney and liver, and related phenotypes are hydrocephalus and bowing of the long bones

Disease Ontology : 12 A Meckel syndrome that has material basis in an autosomal recessive mutation of CEP290 on chromosome 12q21.32.

UniProtKB/Swiss-Prot : 76 Meckel syndrome 4: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.

Related Diseases for Meckel Syndrome, Type 4

Graphical network of the top 20 diseases related to Meckel Syndrome, Type 4:



Diseases related to Meckel Syndrome, Type 4

Symptoms & Phenotypes for Meckel Syndrome, Type 4

Human phenotypes related to Meckel Syndrome, Type 4:

33 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hydrocephalus 33 occasional (7.5%) HP:0000238
2 bowing of the long bones 33 occasional (7.5%) HP:0006487
3 microcephaly 33 occasional (7.5%) HP:0000252
4 cleft palate 33 occasional (7.5%) HP:0000175
5 microphthalmia 33 occasional (7.5%) HP:0000568
6 anencephaly 33 occasional (7.5%) HP:0002323
7 molar tooth sign on mri 33 occasional (7.5%) HP:0002419
8 intrauterine growth retardation 33 HP:0001511
9 atrial septal defect 33 HP:0001631
10 meningocele 33 HP:0002435
11 ventricular septal defect 33 HP:0001629
12 postaxial hand polydactyly 33 HP:0001162
13 dandy-walker malformation 33 HP:0001305
14 encephalocele 33 HP:0002084
15 hypoplasia of the corpus callosum 33 HP:0002079
16 renal cyst 33 HP:0000107
17 agenesis of cerebellar vermis 33 HP:0002335
18 bile duct proliferation 33 HP:0001408

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
intrauterine growth retardation

Head And Neck Eyes:
microphthalmia (rare)

Abdomen Liver:
bile duct proliferation
ductal plate malformations

Skeletal Feet:
polydactyly, postaxial

Genitourinary Kidneys:
cystic dysplasia

Skeletal Limbs:
bowing of the long bones (rare)

Head And Neck Mouth:
cleft palate (in some patients)

Head And Neck Head:
microcephaly (in some patients)

Skeletal Hands:
polydactyly, postaxial

Neurologic Central Nervous System:
dandy-walker malformation (in some patients)
hydrocephalus (in some patients)
cerebellar vermis hypoplasia (in some patients)
encephalocele, occipital
meningocele, occipital
more
Cardiovascular Heart:
septal defects (in some patients)

Clinical features from OMIM:

611134

Drugs & Therapeutics for Meckel Syndrome, Type 4

Drugs for Meckel Syndrome, Type 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 cysteine Phase 2, Phase 3,Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Multi-dose Study for Efficacy, Safety, Tolerability, Exposure of QR-110 in LCA10 Recruiting NCT03913143 Phase 2, Phase 3 QR-110
2 Study to Evaluate QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene Active, not recruiting NCT03140969 Phase 1, Phase 2 QR-110
3 Single Ascending Dose Study in Participants With LCA10 Not yet recruiting NCT03872479 Phase 1, Phase 2 AGN-151587
4 Extension Study to Study PQ-110-001 (NCT03140969) Not yet recruiting NCT03913130 Phase 1, Phase 2 QR-110
5 Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome Completed NCT00873678
6 Natural History Study of CEP290-Related Retinal Degeneration Recruiting NCT03396042

Search NIH Clinical Center for Meckel Syndrome, Type 4

Genetic Tests for Meckel Syndrome, Type 4

Genetic tests related to Meckel Syndrome, Type 4:

# Genetic test Affiliating Genes
1 Meckel Syndrome Type 4 30 CEP290

Anatomical Context for Meckel Syndrome, Type 4

MalaCards organs/tissues related to Meckel Syndrome, Type 4:

42
Bone, Kidney, Liver, Eye

Publications for Meckel Syndrome, Type 4

Articles related to Meckel Syndrome, Type 4:

# Title Authors Year
1
Clinical utility gene card for: Meckel syndrome. ( 21368913 )
2011
2
Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome. ( 17705300 )
2008
3
Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. ( 17345604 )
2007
4
Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. ( 17564974 )
2007

Variations for Meckel Syndrome, Type 4

ClinVar genetic disease variations for Meckel Syndrome, Type 4:

6 (show top 50) (show all 113)
# Gene Variation Type Significance SNP ID Assembly Location
1 CEP290 NM_025114.3(CEP290): c.5668G> T (p.Gly1890Ter) single nucleotide variant Pathogenic rs137852832 GRCh37 Chromosome 12, 88471040: 88471040
2 CEP290 NM_025114.3(CEP290): c.5668G> T (p.Gly1890Ter) single nucleotide variant Pathogenic rs137852832 GRCh38 Chromosome 12, 88077263: 88077263
3 CEP290 NM_025114.3(CEP290): c.2991+1655A> G single nucleotide variant Pathogenic rs281865192 GRCh37 Chromosome 12, 88494960: 88494960
4 CEP290 NM_025114.3(CEP290): c.2991+1655A> G single nucleotide variant Pathogenic rs281865192 GRCh38 Chromosome 12, 88101183: 88101183
5 CEP290 NM_025114.3(CEP290): c.4723A> T (p.Lys1575Ter) single nucleotide variant Pathogenic rs137852834 GRCh37 Chromosome 12, 88477713: 88477713
6 CEP290 NM_025114.3(CEP290): c.4723A> T (p.Lys1575Ter) single nucleotide variant Pathogenic rs137852834 GRCh38 Chromosome 12, 88083936: 88083936
7 CEP290 CEP290, 4-BP DEL, 384TAGA deletion Pathogenic
8 CEP290 CEP290, EX3, T-A, +2 single nucleotide variant Pathogenic
9 CEP290 NM_025114.3(CEP290): c.613C> T (p.Arg205Ter) single nucleotide variant Pathogenic rs137852835 GRCh37 Chromosome 12, 88524101: 88524101
10 CEP290 NM_025114.3(CEP290): c.613C> T (p.Arg205Ter) single nucleotide variant Pathogenic rs137852835 GRCh38 Chromosome 12, 88130324: 88130324
11 CEP290 CEP290, 1-BP DEL, 5489A deletion Pathogenic
12 CEP290 NM_025114.3(CEP290): c.3175delA (p.Ile1059Terfs) deletion Likely pathogenic rs62640570 GRCh38 Chromosome 12, 88093904: 88093904
13 CEP290 NM_025114.3(CEP290): c.3446_3447delAA (p.Lys1149Serfs) deletion Likely pathogenic rs386834155 GRCh37 Chromosome 12, 88486472: 88486473
14 CEP290 NM_025114.3(CEP290): c.1219_1220delAT (p.Met407Glufs) deletion Pathogenic rs386834148 GRCh37 Chromosome 12, 88514913: 88514914
15 CEP290 NM_025114.3(CEP290): c.1219_1220delAT (p.Met407Glufs) deletion Pathogenic rs386834148 GRCh38 Chromosome 12, 88121136: 88121137
16 CEP290 NM_025114.3(CEP290): c.1451delA (p.Lys484Argfs) deletion Pathogenic rs386834149 GRCh37 Chromosome 12, 88513962: 88513962
17 CEP290 NM_025114.3(CEP290): c.1451delA (p.Lys484Argfs) deletion Pathogenic rs386834149 GRCh38 Chromosome 12, 88120185: 88120185
18 CEP290 NM_025114.3(CEP290): c.180+2T> A single nucleotide variant Likely pathogenic rs386834150 GRCh37 Chromosome 12, 88534731: 88534731
19 CEP290 NM_025114.3(CEP290): c.180+2T> A single nucleotide variant Likely pathogenic rs386834150 GRCh38 Chromosome 12, 88140954: 88140954
20 CEP290 NM_025114.3(CEP290): c.1860_1861delAA (p.Asp622Phefs) deletion Likely pathogenic rs386834151 GRCh37 Chromosome 12, 88508923: 88508924
21 CEP290 NM_025114.3(CEP290): c.1860_1861delAA (p.Asp622Phefs) deletion Likely pathogenic rs386834151 GRCh38 Chromosome 12, 88115146: 88115147
22 CEP290 NM_025114.3(CEP290): c.1984C> T (p.Gln662Ter) single nucleotide variant Pathogenic rs386834152 GRCh37 Chromosome 12, 88508265: 88508265
23 CEP290 NM_025114.3(CEP290): c.1984C> T (p.Gln662Ter) single nucleotide variant Pathogenic rs386834152 GRCh38 Chromosome 12, 88114488: 88114488
24 CEP290 NM_025114.3(CEP290): c.289G> T (p.Glu97Ter) single nucleotide variant Likely pathogenic rs386834153 GRCh37 Chromosome 12, 88532930: 88532930
25 CEP290 NM_025114.3(CEP290): c.289G> T (p.Glu97Ter) single nucleotide variant Likely pathogenic rs386834153 GRCh38 Chromosome 12, 88139153: 88139153
26 CEP290 NM_025114.3(CEP290): c.3175delA (p.Ile1059Terfs) deletion Likely pathogenic rs62640570 GRCh37 Chromosome 12, 88487681: 88487681
27 CEP290 NM_025114.3(CEP290): c.3446_3447delAA (p.Lys1149Serfs) deletion Likely pathogenic rs386834155 GRCh38 Chromosome 12, 88092695: 88092696
28 CEP290 NM_025114.3(CEP290): c.381_382delAGinsT (p.Lys127Asnfs) indel Likely pathogenic rs386834156 GRCh37 Chromosome 12, 88530479: 88530480
29 CEP290 NM_025114.3(CEP290): c.381_382delAGinsT (p.Lys127Asnfs) indel Likely pathogenic rs386834156 GRCh38 Chromosome 12, 88136702: 88136703
30 CEP290 NM_025114.3(CEP290): c.384_387delTAGA (p.Asp128Glufs) deletion Pathogenic rs386834157 GRCh37 Chromosome 12, 88530474: 88530477
31 CEP290 NM_025114.3(CEP290): c.384_387delTAGA (p.Asp128Glufs) deletion Pathogenic rs386834157 GRCh38 Chromosome 12, 88136697: 88136700
32 CEP290 NM_025114.3(CEP290): c.5493delA (p.Ala1832Profs) deletion Pathogenic rs386834158 GRCh37 Chromosome 12, 88471567: 88471567
33 CEP290 NM_025114.3(CEP290): c.5493delA (p.Ala1832Profs) deletion Pathogenic rs386834158 GRCh38 Chromosome 12, 88077790: 88077790
34 CEP290 NM_025114.3(CEP290): c.5850delT (p.Phe1950Leufs) deletion Likely pathogenic rs386834159 GRCh37 Chromosome 12, 88465563: 88465563
35 CEP290 NM_025114.3(CEP290): c.5850delT (p.Phe1950Leufs) deletion Likely pathogenic rs386834159 GRCh38 Chromosome 12, 88071786: 88071786
36 CEP290 NM_025114.3(CEP290): c.4250A> G (p.Gln1417Arg) single nucleotide variant Uncertain significance rs201504946 GRCh37 Chromosome 12, 88480220: 88480220
37 CEP290 NM_025114.3(CEP290): c.4250A> G (p.Gln1417Arg) single nucleotide variant Uncertain significance rs201504946 GRCh38 Chromosome 12, 88086443: 88086443
38 CEP290 NM_025114.3(CEP290): c.5611_5614delCAAA (p.Gln1871Valfs) deletion Pathogenic rs727503853 GRCh37 Chromosome 12, 88471094: 88471097
39 CEP290 NM_025114.3(CEP290): c.5611_5614delCAAA (p.Gln1871Valfs) deletion Pathogenic rs727503853 GRCh38 Chromosome 12, 88077317: 88077320
40 CEP290 NM_025114.3(CEP290): c.1665_1666delAA (p.Lys555Asnfs) deletion Pathogenic rs727503855 GRCh37 Chromosome 12, 88512305: 88512306
41 CEP290 NM_025114.3(CEP290): c.1665_1666delAA (p.Lys555Asnfs) deletion Pathogenic rs727503855 GRCh38 Chromosome 12, 88118528: 88118529
42 CEP290 NM_025114.3(CEP290): c.1860_1863delAAGA (p.Arg621Ilefs) deletion Pathogenic rs766608755 GRCh37 Chromosome 12, 88508921: 88508924
43 CEP290 NM_025114.3(CEP290): c.1860_1863delAAGA (p.Arg621Ilefs) deletion Pathogenic rs766608755 GRCh38 Chromosome 12, 88115144: 88115147
44 CEP290 NM_025114.3(CEP290): c.3660G> T (p.Lys1220Asn) single nucleotide variant Uncertain significance rs201982308 GRCh37 Chromosome 12, 88483178: 88483178
45 CEP290 NM_025114.3(CEP290): c.3660G> T (p.Lys1220Asn) single nucleotide variant Uncertain significance rs201982308 GRCh38 Chromosome 12, 88089401: 88089401
46 CEP290 NM_025114.3(CEP290): c.5182G> T (p.Glu1728Ter) single nucleotide variant Pathogenic rs370119681 GRCh37 Chromosome 12, 88474003: 88474003
47 CEP290 NM_025114.3(CEP290): c.5182G> T (p.Glu1728Ter) single nucleotide variant Pathogenic rs370119681 GRCh38 Chromosome 12, 88080226: 88080226
48 CEP290 NM_025114.3(CEP290): c.5284C> T (p.Arg1762Cys) single nucleotide variant Uncertain significance rs373307908 GRCh37 Chromosome 12, 88472949: 88472949
49 CEP290 NM_025114.3(CEP290): c.5284C> T (p.Arg1762Cys) single nucleotide variant Uncertain significance rs373307908 GRCh38 Chromosome 12, 88079172: 88079172
50 CEP290 NM_025114.3(CEP290): c.6604delA (p.Ile2202Leufs) deletion Pathogenic rs758329611 GRCh37 Chromosome 12, 88453716: 88453716

Expression for Meckel Syndrome, Type 4

Search GEO for disease gene expression data for Meckel Syndrome, Type 4.

Pathways for Meckel Syndrome, Type 4

GO Terms for Meckel Syndrome, Type 4

Cellular components related to Meckel Syndrome, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.56 CEP290 MKS1 TMEM138 TMEM231
2 cilium GO:0005929 9.46 CEP290 MKS1 TMEM138 TMEM231
3 centriole GO:0005814 9.37 CEP290 MKS1
4 ciliary basal body GO:0036064 9.32 CEP290 MKS1
5 ciliary transition zone GO:0035869 9.13 CEP290 MKS1 TMEM231
6 MKS complex GO:0036038 8.8 CEP290 MKS1 TMEM231

Biological processes related to Meckel Syndrome, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ciliary basal body-plasma membrane docking GO:0097711 9.26 CEP290 MKS1
2 cilium assembly GO:0060271 9.26 CEP290 MKS1 TMEM138 TMEM231
3 embryonic digit morphogenesis GO:0042733 9.16 MKS1 TMEM231
4 cell projection organization GO:0030030 8.92 CEP290 MKS1 TMEM138 TMEM231

Sources for Meckel Syndrome, Type 4

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
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