JBTS6
MCID: JBR015
MIFTS: 43

Joubert Syndrome 6 (JBTS6)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Joubert Syndrome 6

MalaCards integrated aliases for Joubert Syndrome 6:

Name: Joubert Syndrome 6 57 12 74 29 13 6 44 15 72
Jbts6 57 12 74
Joubert Syndrome, Type 6 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity (see )


HPO:

32
joubert syndrome 6:
Inheritance autosomal recessive inheritance heterogeneous


Classifications:



External Ids:

Disease Ontology 12 DOID:0111001
MedGen 42 C1853153
UMLS 72 C1853153

Summaries for Joubert Syndrome 6

OMIM : 57 Joubert syndrome is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities. Neuroradiologically, Joubert syndrome is characterized by peculiar malformation of the midbrain-hindbrain junction known as the 'molar tooth sign' (MTS) consisting of cerebellar vermis hypoplasia or aplasia, thick and maloriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa (Romano et al., 2006). For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300. (610688)

MalaCards based summary : Joubert Syndrome 6, also known as jbts6, is related to meckel syndrome, type 2 and meckel syndrome, type 4, and has symptoms including ataxia An important gene associated with Joubert Syndrome 6 is TMEM67 (Transmembrane Protein 67), and among its related pathways/superpathways are Regulation of PLK1 Activity at G2/M Transition and Organelle biogenesis and maintenance. Affiliated tissues include kidney, eye and liver, and related phenotypes are intellectual disability and ataxia

Disease Ontology : 12 A Joubert syndrome that has material basis in homozygous or compound heterozygous mutation in the TMEM67 on chromosome 8q22.

UniProtKB/Swiss-Prot : 74 Joubert syndrome 6: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.

Related Diseases for Joubert Syndrome 6

Diseases in the Joubert Syndrome 1 family:

Joubert Syndrome 10 Joubert Syndrome 2
Joubert Syndrome 3 Joubert Syndrome 4
Joubert Syndrome 5 Joubert Syndrome 6
Joubert Syndrome 7 Joubert Syndrome 9
Joubert Syndrome 8 Joubert Syndrome 13
Joubert Syndrome 14 Joubert Syndrome 15
Joubert Syndrome 16 Joubert Syndrome 17
Joubert Syndrome 18 Joubert Syndrome 20
Joubert Syndrome 21 Joubert Syndrome 22
Joubert Syndrome 23 Joubert Syndrome 24
Joubert Syndrome 25 Joubert Syndrome 26
Joubert Syndrome 27 Joubert Syndrome 28
Joubert Syndrome 30 Joubert Syndrome 32
Joubert Syndrome 31 Joubert Syndrome 33
Joubert Syndrome 35

Diseases related to Joubert Syndrome 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 meckel syndrome, type 2 10.1 TMEM67 MKS1
2 meckel syndrome, type 4 10.0 MKS1 CEP290
3 bardet-biedl syndrome 14 10.0 TMEM67 CEP290
4 joubert syndrome with ocular anomalies 10.0 MKS1 AHI1
5 nephronophthisis 19 9.8 TMEM67 NPHP1
6 joubert syndrome 2 9.7 TMEM67 NPHP1
7 joubert syndrome 17 9.7 NPHP1 CEP290
8 nephronophthisis 1 9.7 NPHP1 AHI1
9 coloboma of macula 9.7 TMEM67 CEP290
10 joubert syndrome 3 9.7 NPHP1 AHI1
11 retinal aplasia 9.7 NPHP1 CEP290
12 encephalocele 9.6 TMEM67 MKS1 CEP290
13 nephronophthisis 16 9.6 NPHP1 CEP290
14 pathologic nystagmus 9.6 TMEM67 MKS1 CEP290
15 nephronophthisis 2 9.6 NPHP1 MKS1
16 hydrolethalus syndrome 1 9.5 TMEM67 MKS1 AHI1
17 cystic kidney disease 9.3 TMEM67 NPHP1
18 fundus dystrophy 9.2 NPHP1 CEP290 AHI1
19 bardet-biedl syndrome 13 9.1 TMEM67 MKS1 CEP290 AHI1
20 kidney disease 9.0 TMEM67 NPHP1 CEP290
21 leber congenital amaurosis 8.9 NPHP1 CEP290 AHI1
22 meckel syndrome, type 3 8.9 TMEM67 NPHP1 MKS1 CEP290
23 bardet-biedl syndrome 8.9 TMEM67 NPHP1 MKS1 CEP290
24 nephronophthisis 11 8.8 TMEM67 NPHP1 CEP290 AHI1
25 meckel syndrome, type 6 8.8 TMEM67 NPHP1 MKS1 AHI1
26 senior-loken syndrome 1 8.3 TMEM67 NPHP1 MKS1 CEP290 AHI1
27 meckel syndrome, type 1 8.3 TMEM67 NPHP1 MKS1 CEP290 AHI1
28 nephronophthisis 8.3 TMEM67 NPHP1 MKS1 CEP290 AHI1
29 joubert syndrome 1 8.3 TMEM67 NPHP1 MKS1 CEP290 AHI1

Graphical network of the top 20 diseases related to Joubert Syndrome 6:



Diseases related to Joubert Syndrome 6

Symptoms & Phenotypes for Joubert Syndrome 6

Human phenotypes related to Joubert Syndrome 6:

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 ataxia 32 HP:0001251
3 muscular hypotonia 32 HP:0001252
4 global developmental delay 32 HP:0001263
5 blindness 32 HP:0000618
6 generalized hypotonia 32 HP:0001290
7 hepatic fibrosis 32 HP:0001395
8 chorioretinal coloboma 32 HP:0000567
9 nephronophthisis 32 HP:0000090
10 oculomotor apraxia 32 HP:0000657
11 cerebellar vermis hypoplasia 32 HP:0001320
12 molar tooth sign on mri 32 HP:0002419
13 stage 5 chronic kidney disease 32 HP:0003774
14 retinal degeneration 32 HP:0000546
15 breathing dysregulation 32 HP:0005957
16 elongated superior cerebellar peduncle 32 HP:0011933
17 bile duct proliferation 32 HP:0001408
18 enlarged fossa interpeduncularis 32 HP:0100951
19 thickened superior cerebellar peduncle 32 HP:0002404

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
cerebellar vermis hypoplasia
molar tooth sign on mri
developmental delay
hypotonia
more
Abdomen Liver:
hepatic fibrosis
bile duct proliferation

Respiratory:
breathing dysregulation

Head And Neck Eyes:
blindness
chorioretinal coloboma
oculomotor apraxia
retinal degeneration
abnormal eye movements

Genitourinary Kidneys:
nephronophthisis
end-stage renal failure
microcysts

Clinical features from OMIM:

610688

UMLS symptoms related to Joubert Syndrome 6:


ataxia

MGI Mouse Phenotypes related to Joubert Syndrome 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.65 AHI1 CEP290 MKS1 NPHP1 TMEM67
2 nervous system MP:0003631 9.55 AHI1 CEP290 MKS1 NPHP1 TMEM67
3 renal/urinary system MP:0005367 9.35 AHI1 CEP290 MKS1 NPHP1 TMEM67
4 vision/eye MP:0005391 8.92 AHI1 CEP290 MKS1 NPHP1

Drugs & Therapeutics for Joubert Syndrome 6

Search Clinical Trials , NIH Clinical Center for Joubert Syndrome 6

Cochrane evidence based reviews: joubert syndrome 6

Genetic Tests for Joubert Syndrome 6

Genetic tests related to Joubert Syndrome 6:

# Genetic test Affiliating Genes
1 Joubert Syndrome 6 29 TMEM67

Anatomical Context for Joubert Syndrome 6

MalaCards organs/tissues related to Joubert Syndrome 6:

41
Kidney, Eye, Liver

Publications for Joubert Syndrome 6

Articles related to Joubert Syndrome 6:

(show all 15)
# Title Authors PMID Year
1
The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. 38 8 71
17160906 2007
2
Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. 8 71
21633164 2011
3
Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11). 8 71
19508969 2009
4
Molar tooth sign and superior vermian dysplasia: a radiological, clinical, and genetic study. 8 71
16541367 2006
5
Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome. 71
29891882 2018
6
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. 8
26092869 2015
7
Exome sequencing can improve diagnosis and alter patient management. 71
22700954 2012
8
Clinical utility gene card for: Joubert syndrome. 71
21448235 2011
9
Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). 71
19574260 2010
10
MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement. 71
19058225 2009
11
Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3. 71
17377820 2007
12
Joubert Syndrome 71
20301500 2003
13
Retinitis pigmentosa, hypopituitarism, nephronophthisis, and mild skeletal dysplasia (RHYNS): a new syndrome? 71
9375913 1997
14
Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. 71
2929661 1989
15
EXPANDED PHENOTYPE OF TMEM67 GENE MUTATION (CASE REPORT). 38
28726664 2017

Variations for Joubert Syndrome 6

ClinVar genetic disease variations for Joubert Syndrome 6:

6 (show top 50) (show all 54)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TMEM67 NM_153704.5(TMEM67): c.2315_2322+4delinsG indel Pathogenic rs1554557920 8:94815905-94815917 8:93803677-93803689
2 TMEM67 NM_153704.5(TMEM67): c.1538A> G (p.Tyr513Cys) single nucleotide variant Pathogenic rs137853107 8:94803510-94803510 8:93791282-93791282
3 TMEM67 TMEM67, IVS23+5G-C single nucleotide variant Pathogenic
4 TMEM67 NM_153704.5(TMEM67): c.1634G> A (p.Gly545Glu) single nucleotide variant Pathogenic rs267607114 8:94805484-94805484 8:93793256-93793256
5 TMEM67 NM_153704.5(TMEM67): c.1961-2A> C single nucleotide variant Pathogenic rs758948621 8:94809557-94809557 8:93797329-93797329
6 TMEM67 NM_153704.5(TMEM67): c.622A> T (p.Arg208Ter) single nucleotide variant Pathogenic rs137853108 8:94777845-94777845 8:93765617-93765617
7 TMEM67 NM_153704.5(TMEM67): c.2498T> C (p.Ile833Thr) single nucleotide variant Pathogenic rs267607119 8:94821126-94821126 8:93808898-93808898
8 TMEM67 NM_153704.5(TMEM67): c.2556+1G> T single nucleotide variant Pathogenic rs786200867 8:94821185-94821185 8:93808957-93808957
9 TMEM67 NM_153704.5(TMEM67): c.1769T> C (p.Phe590Ser) single nucleotide variant Pathogenic rs267607115 8:94807731-94807731 8:93795503-93795503
10 TMEM67 NM_153704.5(TMEM67): c.2461G> A (p.Gly821Ser) single nucleotide variant Pathogenic rs267607116 8:94821089-94821089 8:93808861-93808861
11 TMEM67 NM_153704.5(TMEM67): c.2461G> C (p.Gly821Arg) single nucleotide variant Pathogenic rs267607116 8:94821089-94821089 8:93808861-93808861
12 TMEM67 NM_153704.5(TMEM67): c.130C> T (p.Gln44Ter) single nucleotide variant Pathogenic rs267607118 8:94767272-94767272 8:93755044-93755044
13 TMEM67 NM_153704.5(TMEM67): c.755T> C (p.Met252Thr) single nucleotide variant Pathogenic rs202149403 8:94792861-94792861 8:93780633-93780633
14 TMEM67 TMEM67, PRO358LEU undetermined variant Pathogenic
15 TMEM67 NM_153704.5(TMEM67): c.675G> A (p.Trp225Ter) single nucleotide variant Pathogenic rs386834205 8:94784840-94784840 8:93772612-93772612
16 TMEM67 NM_153704.5(TMEM67): c.300C> A (p.Cys100Ter) single nucleotide variant Pathogenic rs751309268 8:94768082-94768082 8:93755854-93755854
17 TMEM67 NM_153704.5(TMEM67): c.389C> G (p.Pro130Arg) single nucleotide variant Pathogenic rs863225226 8:94770787-94770787 8:93758559-93758559
18 TMEM67 NM_153704.5(TMEM67): c.515G> A (p.Arg172Gln) single nucleotide variant Pathogenic rs750950408 8:94777642-94777642 8:93765414-93765414
19 TMEM67 NM_153704.5(TMEM67): c.730A> G (p.Thr244Ala) single nucleotide variant Pathogenic rs863225229 8:94792836-94792836 8:93780608-93780608
20 TMEM67 NM_153704.5(TMEM67): c.769A> G (p.Met257Val) single nucleotide variant Pathogenic rs863225227 8:94792875-94792875 8:93780647-93780647
21 TMEM67 NM_153704.5(TMEM67): c.978+3A> G single nucleotide variant Pathogenic rs775256658 8:94793213-94793213 8:93780985-93780985
22 TMEM67 NM_153704.5(TMEM67): c.1073C> T (p.Pro358Leu) single nucleotide variant Pathogenic rs863225232 8:94794630-94794630 8:93782402-93782402
23 TMEM67 NM_153704.5(TMEM67): c.1081G> T (p.Glu361Ter) single nucleotide variant Pathogenic rs863225237 8:94794638-94794638 8:93782410-93782410
24 TMEM67 NM_153704.5(TMEM67): c.244C> T (p.Pro82Ser) single nucleotide variant Pathogenic rs762543032 8:94768026-94768026 8:93755798-93755798
25 TMEM67 NM_153704.5(TMEM67): c.1126C> G (p.Gln376Glu) single nucleotide variant Pathogenic rs863225231 8:94794683-94794683 8:93782455-93782455
26 TMEM67 NM_153704.5(TMEM67): c.1351C> T (p.Arg451Ter) single nucleotide variant Pathogenic rs116647652 8:94798513-94798513 8:93786285-93786285
27 TMEM67 NM_153704.5(TMEM67): c.1453C> T (p.Pro485Ser) single nucleotide variant Pathogenic rs863225228 8:94800112-94800112 8:93787884-93787884
28 TMEM67 NM_153704.5(TMEM67): c.1674+3A> G single nucleotide variant Pathogenic rs863225224 8:94805527-94805527 8:93793299-93793299
29 TMEM67 NM_153704.5(TMEM67): c.1911C> A (p.Phe637Leu) single nucleotide variant Pathogenic rs863225225 8:94809412-94809412 8:93797184-93797184
30 TMEM67 NM_153704.5(TMEM67): c.2290C> T (p.Arg764Ter) single nucleotide variant Pathogenic rs751517725 8:94815880-94815880 8:93803652-93803652
31 TMEM67 NM_153704.5(TMEM67): c.2368C> A (p.His790Asn) single nucleotide variant Pathogenic rs863225230 8:94817035-94817035 8:93804807-93804807
32 TMEM67 NM_153704.5(TMEM67): c.2522A> C (p.Gln841Pro) single nucleotide variant Pathogenic rs863225234 8:94821150-94821150 8:93808922-93808922
33 TMEM67 NM_153704.5(TMEM67): c.2801G> A (p.Gly934Glu) single nucleotide variant Pathogenic rs863225236 8:94827569-94827569 8:93815341-93815341
34 TMEM67 NM_153704.5(TMEM67): c.2825T> G (p.Phe942Cys) single nucleotide variant Pathogenic rs863225233 8:94827593-94827593 8:93815365-93815365
35 TMEM67 NM_153704.5(TMEM67): c.1321C> T (p.Arg441Cys) single nucleotide variant Pathogenic/Likely pathogenic rs752362727 8:94798483-94798483 8:93786255-93786255
36 TMEM67 NM_153704.5(TMEM67): c.1115C> A (p.Thr372Lys) single nucleotide variant Pathogenic/Likely pathogenic rs863225235 8:94794672-94794672 8:93782444-93782444
37 TMEM67 NM_153704.5(TMEM67): c.579_580del (p.Gly195fs) deletion Pathogenic/Likely pathogenic rs386834202 8:94777802-94777803 8:93765574-93765575
38 TMEM67 NM_153704.5(TMEM67): c.725A> G (p.Asn242Ser) single nucleotide variant Pathogenic/Likely pathogenic rs775883520 8:94792831-94792831 8:93780603-93780603
39 TMEM67 NM_153704.5(TMEM67): c.1046T> C (p.Leu349Ser) single nucleotide variant Pathogenic/Likely pathogenic rs386834180 8:94793953-94793953 8:93781725-93781725
40 TMEM67 NM_153704.5(TMEM67): c.1843T> C (p.Cys615Arg) single nucleotide variant Pathogenic/Likely pathogenic rs201893408 8:94808198-94808198 8:93795970-93795970
41 TMEM67 NM_153704.5(TMEM67): c.651+2T> G single nucleotide variant Pathogenic/Likely pathogenic rs199821258 8:94777876-94777876 8:93765648-93765648
42 TMEM67 NM_153704.5(TMEM67): c.1575+5G> A single nucleotide variant Likely pathogenic rs1554555063 8:94803552-94803552 8:93791324-93791324
43 TMEM67 NM_153704.5(TMEM67): c.2086C> T (p.Leu696Phe) single nucleotide variant Likely pathogenic rs863225238 8:94809684-94809684 8:93797456-93797456
44 TMEM67 NM_153704.5(TMEM67): c.1353del (p.Glu452fs) deletion Likely pathogenic rs749435317 8:94798515-94798515 8:93786287-93786287
45 TMEM67 NM_153704.5(TMEM67): c.2661+5G> A single nucleotide variant Likely pathogenic rs863225239 8:94821394-94821394 8:93809166-93809166
46 TMEM67 NM_153704.5(TMEM67): c.2322+5del deletion Likely pathogenic rs863225240 8:94815917-94815917 8:93803689-93803689
47 TMEM67 NM_153704.5(TMEM67): c.245C> G (p.Pro82Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs772437766 8:94768027-94768027 8:93755799-93755799
48 TMEM67 NM_153704.5(TMEM67): c.2322+2dup duplication Conflicting interpretations of pathogenicity rs386834192 8:94815914-94815914 8:93803686-93803686
49 TMEM67 NM_153704.5(TMEM67): c.297G> T (p.Lys99Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs797046045 8:94768079-94768079 8:93755851-93755851
50 TMEM67 NM_153704.5(TMEM67): c.1421T> C (p.Leu474Pro) single nucleotide variant Uncertain significance rs1554554236 8:94800080-94800080 8:93787852-93787852

UniProtKB/Swiss-Prot genetic disease variations for Joubert Syndrome 6:

74
# Symbol AA change Variation ID SNP ID
1 TMEM67 p.Tyr513Cys VAR_031987 rs137853107
2 TMEM67 p.Gly545Glu VAR_031988 rs267607114
3 TMEM67 p.Met252Thr VAR_062313 rs202149403
4 TMEM67 p.Pro358Leu VAR_063791 rs863225232
5 TMEM67 p.Ile833Thr VAR_063801 rs267607119
6 TMEM67 p.Asp711Ala VAR_075699 rs781383498

Expression for Joubert Syndrome 6

Search GEO for disease gene expression data for Joubert Syndrome 6.

Pathways for Joubert Syndrome 6

GO Terms for Joubert Syndrome 6

Cellular components related to Joubert Syndrome 6 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.72 TMEM67 NPHP1 MKS1 CEP290 AHI1
2 centrosome GO:0005813 9.67 TMEM67 MKS1 CEP290 AHI1
3 cell projection GO:0042995 9.65 TMEM67 NPHP1 MKS1 CEP290 AHI1
4 centriole GO:0005814 9.61 MKS1 CEP290 AHI1
5 ciliary basal body GO:0036064 9.58 MKS1 CEP290 AHI1
6 cell-cell junction GO:0005911 9.49 NPHP1 AHI1
7 adherens junction GO:0005912 9.48 NPHP1 AHI1
8 photoreceptor connecting cilium GO:0032391 9.46 NPHP1 CEP290
9 cilium GO:0005929 9.35 TMEM67 NPHP1 MKS1 CEP290 AHI1
10 ciliary transition zone GO:0035869 9.33 TMEM67 MKS1 CEP290
11 MKS complex GO:0036038 8.92 TMEM67 MKS1 CEP290 AHI1

Biological processes related to Joubert Syndrome 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cilium assembly GO:0060271 9.46 TMEM67 MKS1 CEP290 AHI1
2 cell projection organization GO:0030030 9.35 TMEM67 NPHP1 MKS1 CEP290 AHI1
3 hindbrain development GO:0030902 9.26 CEP290 AHI1
4 ciliary basal body-plasma membrane docking GO:0097711 9.02 TMEM67 NPHP1 MKS1 CEP290 AHI1

Sources for Joubert Syndrome 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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