WARBM3
MCID: WRB004
MIFTS: 43

Warburg Micro Syndrome 3 (WARBM3)

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

Aliases & Classifications for Warburg Micro Syndrome 3

Summaries for Warburg Micro Syndrome 3

OMIM : 56 Warburg Micro syndrome is a rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism (summary by Morris-Rosendahl et al., 2010). For a discussion of genetic heterogeneity of Warburg Micro syndrome, see 600118. (614222)

MalaCards based summary : Warburg Micro Syndrome 3, also known as micro syndrome 3, is related to spastic cerebral palsy and rab18 deficiency, and has symptoms including seizures An important gene associated with Warburg Micro Syndrome 3 is RAB18 (RAB18, Member RAS Oncogene Family), and among its related pathways/superpathways are Vesicle-mediated transport and Sertoli-Sertoli Cell Junction Dynamics. Affiliated tissues include testes and cortex, and related phenotypes are narrow palate and macrotia

Disease Ontology : 12 A Warburg micro syndrome that has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the RAB18 gene on chromosome 10p12.

UniProtKB/Swiss-Prot : 73 Warburg micro syndrome 3: A rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism.

Related Diseases for Warburg Micro Syndrome 3

Graphical network of the top 20 diseases related to Warburg Micro Syndrome 3:



Diseases related to Warburg Micro Syndrome 3

Symptoms & Phenotypes for Warburg Micro Syndrome 3

Human phenotypes related to Warburg Micro Syndrome 3:

31 (show all 35)
# Description HPO Frequency HPO Source Accession
1 narrow palate 31 HP:0000189
2 macrotia 31 HP:0000400
3 short nose 31 HP:0003196
4 optic atrophy 31 HP:0000648
5 flexion contracture 31 HP:0001371
6 brachycephaly 31 HP:0000248
7 spastic tetraplegia 31 HP:0002510
8 decreased muscle mass 31 HP:0003199
9 nystagmus 31 HP:0000639
10 wide intermamillary distance 31 HP:0006610
11 postnatal growth retardation 31 HP:0008897
12 micrognathia 31 HP:0000347
13 kyphoscoliosis 31 HP:0002751
14 cerebral cortical atrophy 31 HP:0002120
15 downturned corners of mouth 31 HP:0002714
16 clinodactyly of the 5th finger 31 HP:0004209
17 micropenis 31 HP:0000054
18 microphthalmia 31 HP:0000568
19 ventriculomegaly 31 HP:0002119
20 low anterior hairline 31 HP:0000294
21 blepharophimosis 31 HP:0000581
22 microcornea 31 HP:0000482
23 decreased testicular size 31 HP:0008734
24 polymicrogyria 31 HP:0002126
25 scrotal hypoplasia 31 HP:0000046
26 hypoplasia of the corpus callosum 31 HP:0002079
27 intellectual disability, profound 31 HP:0002187
28 postnatal microcephaly 31 HP:0005484
29 muscular hypotonia of the trunk 31 HP:0008936
30 developmental cataract 31 HP:0000519
31 ankle clonus 31 HP:0011448
32 hypertrichosis 31 HP:0000998
33 hypoplastic labia minora 31 HP:0000064
34 shallow anterior chamber 31 HP:0000594
35 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Mouth:
narrow palate
downturned corners of mouth

Head And Neck Nose:
short nose
prominent root of nose

Head And Neck Eyes:
nystagmus
microphthalmia
microcornea
shallow anterior chamber
cataract, congenital
more
Head And Neck Face:
micrognathia
short prominent overhanging philtrum

Skin Nails Hair Hair:
low anterior hairline
centrally placed hair whorl
hypertrichosis of upper back

Chest Breasts:
widely spaced nipples

Head And Neck Ears:
large ears

Skeletal Hands:
flexion contractures of fingers
cortical thumbs
bilateral fifth finger clinodactyly

Head And Neck Teeth:
prominent secondary alveolar ridges

Skeletal Limbs:
distal limb contractures

Muscle Soft Tissue:
decreased muscle mass, especially distally

Neurologic Central Nervous System:
seizures
polymicrogyria
enlarged ventricles
hypoplastic corpus callosum
cortical atrophy
more
Head And Neck Head:
brachycephaly
postnatal microcephaly

Growth Height:
postnatal growth retardation

Skeletal Spine:
kyphoscoliosis

Neurologic Peripheral Nervous System:
ankle clonus
increased deep tendon responses of lower extremities

Skeletal Skull:
microcephaly, postnatal

Genitourinary External Genitalia Male:
hypoplastic scrotum
small penis

Genitourinary Internal Genitalia Male:
small testes
retractile testes
soft testes

Genitourinary External Genitalia Female:
fused, hypoplastic labia minora

Skeletal Feet:
externally rotated feet in valgus position

Clinical features from OMIM:

614222

UMLS symptoms related to Warburg Micro Syndrome 3:


seizures

MGI Mouse Phenotypes related to Warburg Micro Syndrome 3:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.36 EXO1 GSK3B HACD1 PRNP RAB2A RAB3A

Drugs & Therapeutics for Warburg Micro Syndrome 3

Search Clinical Trials , NIH Clinical Center for Warburg Micro Syndrome 3

Genetic Tests for Warburg Micro Syndrome 3

Genetic tests related to Warburg Micro Syndrome 3:

# Genetic test Affiliating Genes
1 Warburg Micro Syndrome 3 29 RAB18

Anatomical Context for Warburg Micro Syndrome 3

MalaCards organs/tissues related to Warburg Micro Syndrome 3:

40
Testes, Cortex

Publications for Warburg Micro Syndrome 3

Articles related to Warburg Micro Syndrome 3:

# Title Authors PMID Year
1
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. 6 56
23420520 2013
2
Loss-of-function mutations in RAB18 cause Warburg micro syndrome. 56 6
21473985 2011
3
MICRO syndrome: an entity distinct from COFS syndrome. 6 56
15216543 2004
4
RAB18 Deficiency 6
29300443 2018
5
New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. 56
20512159 2010
6
Micro syndrome in Muslim Pakistan children. 56
11237903 2001

Variations for Warburg Micro Syndrome 3

ClinVar genetic disease variations for Warburg Micro Syndrome 3:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAB18 NM_021252.5(RAB18):c.71T>A (p.Leu24Gln)SNV Pathogenic 30247 rs387906832 10:27798806-27798806 10:27509877-27509877
2 RAB18 RAB18, EX2DELdeletion Pathogenic 30248
3 RAB18 NM_021252.5(RAB18):c.274_276AGA[1] (p.Arg93del)short repeat Pathogenic 30249 rs587776875 10:27822677-27822679 10:27533748-27533750
4 RAB18 NM_021252.5(RAB18):c.619T>C (p.Ter207Gln)SNV Pathogenic 30250 rs387906833 10:27826978-27826978 10:27538049-27538049
5 RAB18 NM_021252.5(RAB18):c.284C>G (p.Thr95Arg)SNV Pathogenic 100768 rs587777151 10:27822688-27822688 10:27533759-27533759
6 RAB18 NM_021252.5(RAB18):c.*764A>GSNV Uncertain significance 299836 rs749045175 10:27827744-27827744 10:27538815-27538815
7 RAB18 NM_021252.5(RAB18):c.*890G>ASNV Uncertain significance 299837 rs539207601 10:27827870-27827870 10:27538941-27538941
8 RAB18 NM_021252.5(RAB18):c.*956A>CSNV Uncertain significance 299838 rs770434733 10:27827936-27827936 10:27539007-27539007
9 RAB18 NM_021252.5(RAB18):c.*992C>ASNV Uncertain significance 299839 rs763254596 10:27827972-27827972 10:27539043-27539043
10 RAB18 NM_021252.5(RAB18):c.*1136G>ASNV Uncertain significance 299841 rs753649409 10:27828116-27828116 10:27539187-27539187
11 RAB18 NM_021252.5(RAB18):c.*1141T>CSNV Uncertain significance 299842 rs751708158 10:27828121-27828121 10:27539192-27539192
12 RAB18 NM_021252.5(RAB18):c.*3543G>ASNV Uncertain significance 878658 10:27830523-27830523 10:27541594-27541594
13 RAB18 NM_021252.5(RAB18):c.*3766C>ASNV Uncertain significance 879257 10:27830746-27830746 10:27541817-27541817
14 RAB18 NM_021252.5(RAB18):c.*3832C>ASNV Uncertain significance 879258 10:27830812-27830812 10:27541883-27541883
15 RAB18 NM_021252.5(RAB18):c.*3906G>ASNV Uncertain significance 879259 10:27830886-27830886 10:27541957-27541957
16 RAB18 NM_021252.5(RAB18):c.*407G>TSNV Uncertain significance 878560 10:27827387-27827387 10:27538458-27538458
17 RAB18 NM_021252.5(RAB18):c.*419G>ASNV Uncertain significance 878561 10:27827399-27827399 10:27538470-27538470
18 RAB18 NM_021252.5(RAB18):c.*4008C>TSNV Uncertain significance 880445 10:27830988-27830988 10:27542059-27542059
19 RAB18 NM_021252.5(RAB18):c.*4038A>TSNV Uncertain significance 880446 10:27831018-27831018 10:27542089-27542089
20 RAB18 NM_021252.5(RAB18):c.*560C>TSNV Uncertain significance 879152 10:27827540-27827540 10:27538611-27538611
21 RAB18 NM_021252.5(RAB18):c.*635G>ASNV Uncertain significance 879153 10:27827615-27827615 10:27538686-27538686
22 RAB18 NM_021252.5(RAB18):c.*822T>CSNV Uncertain significance 880354 10:27827802-27827802 10:27538873-27538873
23 RAB18 NM_021252.5(RAB18):c.*906A>GSNV Uncertain significance 880355 10:27827886-27827886 10:27538957-27538957
24 RAB18 NM_021252.5(RAB18):c.*946G>TSNV Uncertain significance 880356 10:27827926-27827926 10:27538997-27538997
25 RAB18 NM_021252.5(RAB18):c.*1041A>GSNV Uncertain significance 877584 10:27828021-27828021 10:27539092-27539092
26 RAB18 NM_021252.5(RAB18):c.*1047T>GSNV Uncertain significance 877585 10:27828027-27828027 10:27539098-27539098
27 RAB18 NM_021252.5(RAB18):c.*1110A>GSNV Uncertain significance 877586 10:27828090-27828090 10:27539161-27539161
28 RAB18 NM_021252.5(RAB18):c.*1452G>ASNV Uncertain significance 878601 10:27828432-27828432 10:27539503-27539503
29 RAB18 NM_021252.5(RAB18):c.*1589T>CSNV Uncertain significance 878602 10:27828569-27828569 10:27539640-27539640
30 RAB18 NM_021252.5(RAB18):c.*1779A>TSNV Uncertain significance 878603 10:27828759-27828759 10:27539830-27539830
31 RAB18 NM_021252.5(RAB18):c.*1800A>GSNV Uncertain significance 879199 10:27828780-27828780 10:27539851-27539851
32 RAB18 NM_021252.5(RAB18):c.*1842A>GSNV Uncertain significance 879200 10:27828822-27828822 10:27539893-27539893
33 RAB18 NM_021252.5(RAB18):c.*2085A>CSNV Uncertain significance 879201 10:27829065-27829065 10:27540136-27540136
34 RAB18 NC_000010.11:g.27504220G>ASNV Uncertain significance 879100 10:27793149-27793149 10:27504220-27504220
35 RAB18 NM_021252.5(RAB18):c.422G>A (p.Arg141Gln)SNV Uncertain significance 877531 10:27822900-27822900 10:27533971-27533971
36 RAB18 NM_021252.5(RAB18):c.*8G>ASNV Uncertain significance 877532 10:27826988-27826988 10:27538059-27538059
37 RAB18 NM_021252.5(RAB18):c.*150C>ASNV Uncertain significance 877533 10:27827130-27827130 10:27538201-27538201
38 RAB18 NM_021252.5(RAB18):c.*2327T>CSNV Uncertain significance 880404 10:27829307-27829307 10:27540378-27540378
39 RAB18 NM_021252.5(RAB18):c.*2985T>GSNV Uncertain significance 877644 10:27829965-27829965 10:27541036-27541036
40 RAB18 NM_021252.5(RAB18):c.*3222C>TSNV Uncertain significance 878654 10:27830202-27830202 10:27541273-27541273
41 RAB18 NM_021252.5(RAB18):c.*3227A>GSNV Uncertain significance 878655 10:27830207-27830207 10:27541278-27541278
42 RAB18 NM_021252.5(RAB18):c.*3330G>CSNV Uncertain significance 878656 10:27830310-27830310 10:27541381-27541381
43 RAB18 NM_021252.5(RAB18):c.*1696T>ASNV Uncertain significance 299848 rs886046973 10:27828676-27828676 10:27539747-27539747
44 RAB18 NM_021252.5(RAB18):c.*1845G>TSNV Uncertain significance 299849 rs186064414 10:27828825-27828825 10:27539896-27539896
45 RAB18 NM_021252.5(RAB18):c.*1895G>CSNV Uncertain significance 299850 rs746613469 10:27828875-27828875 10:27539946-27539946
46 RAB18 NM_021252.5(RAB18):c.*382C>TSNV Uncertain significance 299828 rs886046971 10:27827362-27827362 10:27538433-27538433
47 RAB18 NM_021252.5(RAB18):c.*2420C>ASNV Uncertain significance 299855 rs770379811 10:27829400-27829400 10:27540471-27540471
48 RAB18 NM_021252.5(RAB18):c.*2788C>TSNV Uncertain significance 299860 rs886046974 10:27829768-27829768 10:27540839-27540839
49 RAB18 NM_021252.5(RAB18):c.*4039A>CSNV Uncertain significance 299882 rs886046982 10:27831019-27831019 10:27542090-27542090
50 RAB18 NM_021252.5(RAB18):c.68+10A>GSNV Uncertain significance 299815 rs886046965 10:27793376-27793376 10:27504447-27504447

UniProtKB/Swiss-Prot genetic disease variations for Warburg Micro Syndrome 3:

73
# Symbol AA change Variation ID SNP ID
1 RAB18 p.Leu24Gln VAR_066495 rs387906832

Expression for Warburg Micro Syndrome 3

Search GEO for disease gene expression data for Warburg Micro Syndrome 3.

Pathways for Warburg Micro Syndrome 3

Pathways related to Warburg Micro Syndrome 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.97 TBC1D20 TBC1D1 RAB3GAP2 RAB3GAP1 RAB3A RAB18
2
Show member pathways
12.56 RAB3D RAB3A RAB2A RAB18 GSK3B
3 11.84 RAB3D RAB3A RAB2A RAB18
4 11.21 RAB3GAP2 RAB3GAP1 RAB3A RAB18
5 10.78 RAB3GAP2 RAB3GAP1 RAB18
6 10.74 RAB3D RAB3A RAB2A RAB18

GO Terms for Warburg Micro Syndrome 3

Cellular components related to Warburg Micro Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynapse GO:0098794 9.43 RAB3GAP1 PRNP GSK3B
2 endomembrane system GO:0012505 9.26 RAB3D RAB3A RAB2A RAB18
3 endoplasmic reticulum membrane GO:0005789 9.17 TYRO3 TBC1D20 RAB3GAP2 RAB3GAP1 RAB2A RAB18
4 endoplasmic reticulum tubular network GO:0071782 9.16 RAB3GAP1 RAB18

Biological processes related to Warburg Micro Syndrome 3 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.72 TBC1D20 RAB3GAP2 RAB3GAP1 GSK3B AGFG1
2 vesicle docking involved in exocytosis GO:0006904 9.52 RAB3D RAB3A
3 negative regulation of calcineurin-NFAT signaling cascade GO:0070885 9.51 PRNP GSK3B
4 acrosome assembly GO:0001675 9.49 TBC1D20 AGFG1
5 regulation of short-term neuronal synaptic plasticity GO:0048172 9.48 RAB3GAP1 RAB3A
6 positive regulation of autophagosome assembly GO:2000786 9.46 RAB3GAP2 RAB3GAP1
7 positive regulation of regulated secretory pathway GO:1903307 9.43 RAB3D RAB3A
8 positive regulation of endoplasmic reticulum tubular network organization GO:1903373 9.4 RAB3GAP2 RAB3GAP1
9 positive regulation of protein lipidation GO:1903061 9.37 RAB3GAP2 RAB3GAP1
10 lipid droplet organization GO:0034389 9.33 TBC1D20 RAB3GAP1 RAB18
11 establishment of protein localization to endoplasmic reticulum membrane GO:0097051 9.26 RAB3GAP2 RAB3GAP1
12 Rab protein signal transduction GO:0032482 9.26 RAB3D RAB3A RAB2A RAB18
13 intracellular protein transport GO:0006886 9.1 TBC1D1 RAB3GAP2 RAB3D RAB3A RAB2A RAB18

Molecular functions related to Warburg Micro Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.87 TYRO3 STK38L RAB3D RAB3A RAB2A RAB18
2 GTP binding GO:0005525 9.67 RAB3D RAB3A RAB2A RAB18
3 GTPase activity GO:0003924 9.46 RAB3D RAB3A RAB2A RAB18
4 Rab guanyl-nucleotide exchange factor activity GO:0017112 9.43 RAB3GAP2 RAB3GAP1
5 GTP-dependent protein binding GO:0030742 9.4 RAB3D RAB3A
6 myosin V binding GO:0031489 9.26 RAB3D RAB3A
7 Rab GTPase binding GO:0017137 9.26 TBC1D20 TBC1D1 RAB3GAP2 RAB3GAP1
8 GTPase activator activity GO:0005096 9.02 TBC1D20 TBC1D1 RAB3GAP2 RAB3GAP1 AGFG1

Sources for Warburg Micro Syndrome 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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