MCID: RB1001
MIFTS: 22

Rab18 Deficiency

Categories: Eye diseases, Neuronal diseases, Reproductive diseases

Aliases & Classifications for Rab18 Deficiency

MalaCards integrated aliases for Rab18 Deficiency:

Name: Rab18 Deficiency 25 43

Classifications:



Summaries for Rab18 Deficiency

MedlinePlus Genetics : 43 RAB18 deficiency causes two conditions with similar signs and symptoms that primarily affect the eyes, brain, and reproductive system. These two conditions, called Warburg micro syndrome and Martsolf syndrome, were once thought to be distinct disorders but are now considered to be part of the same disease spectrum because of their similar features and shared genetic cause.Warburg micro syndrome is the more severe condition. Individuals with this condition have several eye problems from birth, including clouding of the lenses of the eyes (cataracts), abnormally small eyes (microphthalmia), and small corneas (microcornea). The lens is a structure at the front of the eye that helps focus light, and the cornea is the outer covering of the eye. In addition, the pupils of the eyes may be abnormally small (constricted), and they may not enlarge (dilate) in low light. Individuals with Warburg micro syndrome also have degeneration of the nerves that carry visual information from the eyes to the brain (optic atrophy). The eye problems impair vision in affected individuals.People with Warburg micro syndrome have severe intellectual disability and other neurological features due to problems with growth and development of the brain. Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy. By early childhood, they develop muscle stiffness (spasticity) and joint deformities (contractures) that restrict movement in the legs. The muscle problems worsen (progress) to include the arms and lead to paralysis of all four limbs (spastic quadriplegia). Eventually, breathing may be impaired. The brain abnormalities can contribute to vision problems (cortical visual impairment). Individuals with Warburg micro syndrome may also have recurrent seizures (epilepsy).Some people with Warburg micro syndrome have reduced production of the hormones that direct sexual development (hypogonadotropic hypogonadism). The shortage of these hormones impairs normal development of reproductive organs. Affected males may have a small penis (micropenis) or undescended testes (cryptorchidism). Affected females may have underdeveloped internal genital folds (labia minora) or a small clitoris or vaginal opening (introitus).Martsolf syndrome affects the same body systems as Warburg micro syndrome but is usually less severe. Individuals with Martsolf syndrome have cataracts, microphthalmia, and small pupils. They have milder optic atrophy and cortical visual impairment than people with Warburg micro syndrome. Intellectual disability is mild to moderate in people with Martsolf syndrome. While language and motor skills, such as sitting and walking, are delayed, affected individuals usually acquire them. Hypotonia is common in infants with Martsolf syndrome, although spasticity worsens more slowly than in individuals with Warburg micro syndrome, and it usually affects only the legs and feet. Hypogonadotropic hypogonadism can also occur in individuals with Martsolf syndrome.Neither Warburg micro syndrome nor Martsolf syndrome affect the life expectancy of affected individuals.

MalaCards based summary : Rab18 Deficiency is related to warburg micro syndrome and warburg micro syndrome 1. An important gene associated with Rab18 Deficiency is RAB18 (RAB18, Member RAS Oncogene Family), and among its related pathways/superpathways are Vesicle-mediated transport and Golgi-to-ER retrograde transport. Affiliated tissues include eye, brain and testes, and related phenotype is nervous system.

GeneReviews: NBK475670

Related Diseases for Rab18 Deficiency

Graphical network of the top 20 diseases related to Rab18 Deficiency:



Diseases related to Rab18 Deficiency

Symptoms & Phenotypes for Rab18 Deficiency

MGI Mouse Phenotypes related to Rab18 Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 8.92 RAB18 RAB3GAP1 RAB3GAP2 TBC1D20

Drugs & Therapeutics for Rab18 Deficiency

Search Clinical Trials , NIH Clinical Center for Rab18 Deficiency

Genetic Tests for Rab18 Deficiency

Anatomical Context for Rab18 Deficiency

MalaCards organs/tissues related to Rab18 Deficiency:

40
Eye, Brain, Testes

Publications for Rab18 Deficiency

Articles related to Rab18 Deficiency:

(show all 43)
# Title Authors PMID Year
1
Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation. 25 61
26063829 2015
2
The RAB GTPase RAB18 modulates macroautophagy and proteostasis. 25
28342870 2017
3
Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract. 25
27878435 2017
4
Early detection of bilateral cataracts in utero may represent a manifestation of severe congenital disease. 25
27256633 2016
5
Consanguinity as an Adjunct Diagnostic Tool. 25
26138576 2016
6
Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg Micro syndrome. 25
26421802 2016
7
Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. 25
26846091 2016
8
Warburg micro syndrome type 1 associated with peripheral neuropathy and cardiomyopathy. 25
27764520 2016
9
Deletion 1q43-44 in a patient with clinical diagnosis of Warburg-Micro syndrome. 25
25899426 2015
10
RECURRENT RAB3GAP1 MUTATIONS IN THE TURKISH POPULATION. 25
26852512 2015
11
Two novel homozygous RAB3GAP1 mutations cause Warburg micro syndrome. 25
27081543 2015
12
A highly conserved program of neuronal microexons is misregulated in autistic brains. 25
25525873 2014
13
Large homozygous RAB3GAP1 gene microdeletion causes Warburg micro syndrome 1. 25
25332050 2014
14
Rab18 and a Rab18 GEF complex are required for normal ER structure. 25
24891604 2014
15
Exome sequencing as a diagnostic tool for pediatric-onset ataxia. 25
24108619 2014
16
Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. 25
24239381 2013
17
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. 25
23420520 2013
18
Catalytic mechanism of a mammalian Rab·RabGAP complex in atomic detail. 25
23236136 2012
19
Warburg micro syndrome in two children from a highly inbred Turkish family. 25
22876574 2012
20
Warburg Micro syndrome. 25
22768674 2012
21
Illuminating the functional and structural repertoire of human TBC/RABGAPs. 25
22251903 2012
22
Loss-of-function mutations in RAB18 cause Warburg micro syndrome. 25
21473985 2011
23
A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. 25
20967465 2011
24
Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity. 25
21829560 2011
25
New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. 25
20512159 2010
26
Rab18 and Rab43 have key roles in ER-Golgi trafficking. 25
18664496 2008
27
Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells. 25
17684057 2007
28
Rab18 inhibits secretory activity in neuroendocrine cells by interacting with secretory granules. 25
17488286 2007
29
Warburg Micro syndrome in a Turkish boy. 25
17351351 2007
30
Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation. 25
17114793 2007
31
Phenotypic variability in Micro syndrome: report of new cases. 25
18286824 2007
32
Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome. 25
16532399 2006
33
Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. 25
16207721 2005
34
Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. 25
15914536 2005
35
Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. 25
15696165 2005
36
MICRO syndrome: an entity distinct from COFS syndrome. 25
15216543 2004
37
Biochemical characterization of Rab3-GTPase-activating protein reveals a mechanism similar to that of Ras-GAP. 25
10859313 2000
38
Polymicrogyria and motor neuropathy in Micro syndrome. 25
11071150 2000
39
Autosomal recessive microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism. Micro syndrome. 25
8249951 1993
40
Severe mental retardation, cataracts, short stature, and primary hypogonadism in two brothers. 25
677168 1978
41
Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights. 61
32740904 2020
42
RAB18 Deficiency 61
29300443 2018
43
ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon degeneration caused by a deletion in Rab18. 61
25779931 2015

Variations for Rab18 Deficiency

Expression for Rab18 Deficiency

Search GEO for disease gene expression data for Rab18 Deficiency.

Pathways for Rab18 Deficiency

GO Terms for Rab18 Deficiency

Cellular components related to Rab18 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid droplet GO:0005811 9.16 RAB3GAP1 RAB18
2 endoplasmic reticulum tubular network GO:0071782 8.96 RAB3GAP1 RAB18
3 endoplasmic reticulum membrane GO:0005789 8.92 TBC1D20 RAB3GAP2 RAB3GAP1 RAB18

Biological processes related to Rab18 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.54 TBC1D20 RAB3GAP2 RAB3GAP1
2 brain development GO:0007420 9.46 RAB3GAP1 RAB18
3 regulation of GTPase activity GO:0043087 9.43 RAB3GAP2 RAB3GAP1
4 camera-type eye development GO:0043010 9.4 TBC1D20 RAB3GAP1
5 positive regulation of autophagosome assembly GO:2000786 9.32 RAB3GAP2 RAB3GAP1
6 positive regulation of endoplasmic reticulum tubular network organization GO:1903373 9.26 RAB3GAP2 RAB3GAP1
7 positive regulation of protein lipidation GO:1903061 9.16 RAB3GAP2 RAB3GAP1
8 establishment of protein localization to endoplasmic reticulum membrane GO:0097051 8.96 RAB3GAP2 RAB3GAP1
9 lipid droplet organization GO:0034389 8.8 TBC1D20 RAB3GAP1 RAB18

Molecular functions related to Rab18 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 9.16 RAB3GAP2 RAB3GAP1
2 small GTPase binding GO:0031267 9.13 TBC1D20 RAB3GAP2 RAB3GAP1
3 GTPase activator activity GO:0005096 8.8 TBC1D20 RAB3GAP2 RAB3GAP1

Sources for Rab18 Deficiency

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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