WARBM4
MCID: WRB005
MIFTS: 37

Warburg Micro Syndrome 4 (WARBM4)

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

Aliases & Classifications for Warburg Micro Syndrome 4

MalaCards integrated aliases for Warburg Micro Syndrome 4:

Name: Warburg Micro Syndrome 4 57 12 72 29 6 15 70
Warbm4 57 12 72
Warburg Micro Syndrome, Type 4 39
Micro Syndrome 4 12

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
congenital hypotonia from 8 to 12 months, then progressive spasticity resulting in contractures and spastic quadriplegia


HPO:

31
warburg micro syndrome 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Warburg Micro Syndrome 4

OMIM® : 57 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. (615663) (Updated 20-May-2021)

MalaCards based summary : Warburg Micro Syndrome 4, also known as warbm4, is related to spastic cerebral palsy and lens disease. An important gene associated with Warburg Micro Syndrome 4 is TBC1D20 (TBC1 Domain Family Member 20), and among its related pathways/superpathways are Vesicle-mediated transport and Golgi-to-ER retrograde transport. Affiliated tissues include eye and testes, and related phenotypes are brachycephaly and hirsutism

Disease Ontology : 12 A Warburg micro syndrome that has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the TBC1D20 gene on chromosome 20p13.

UniProtKB/Swiss-Prot : 72 Warburg micro syndrome 4: A form of Warburg micro syndrome, 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 4

Graphical network of the top 20 diseases related to Warburg Micro Syndrome 4:



Diseases related to Warburg Micro Syndrome 4

Symptoms & Phenotypes for Warburg Micro Syndrome 4

Human phenotypes related to Warburg Micro Syndrome 4:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 brachycephaly 31 occasional (7.5%) HP:0000248
2 hirsutism 31 occasional (7.5%) HP:0001007
3 seizure 31 occasional (7.5%) HP:0001250
4 ptosis 31 HP:0000508
5 wide nasal bridge 31 HP:0000431
6 optic atrophy 31 HP:0000648
7 flexion contracture 31 HP:0001371
8 spastic tetraplegia 31 HP:0002510
9 decreased muscle mass 31 HP:0003199
10 intellectual disability, severe 31 HP:0010864
11 cryptorchidism 31 HP:0000028
12 cerebral cortical atrophy 31 HP:0002120
13 glaucoma 31 HP:0000501
14 narrow mouth 31 HP:0000160
15 micropenis 31 HP:0000054
16 microphthalmia 31 HP:0000568
17 deeply set eye 31 HP:0000490
18 low anterior hairline 31 HP:0000294
19 microcornea 31 HP:0000482
20 decreased testicular size 31 HP:0008734
21 scrotal hypoplasia 31 HP:0000046
22 severe postnatal growth retardation 31 HP:0008850
23 hypoplasia of the corpus callosum 31 HP:0002079
24 cerebellar atrophy 31 HP:0001272
25 postnatal microcephaly 31 HP:0005484
26 developmental cataract 31 HP:0000519
27 frontoparietal polymicrogyria 31 HP:0007095

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
ptosis
glaucoma
microphthalmia
microcornea
deep-set eyes
more
Muscle Soft Tissue:
decreased muscle mass

Head And Neck Mouth:
narrow mouth

Skin Nails Hair Hair:
low anterior hairline
hirsutism (rare)

Head And Neck Head:
postnatal microcephaly
brachycephaly (in some patients)

Neurologic Central Nervous System:
hypoplastic corpus callosum
seizures (in some patients)
cortical atrophy
spastic quadriplegia
mental retardation, severe to profound
more
Skeletal Limbs:
contractures

Head And Neck Nose:
wide nasal bridge
prominent subnasal region

Genitourinary Internal Genitalia Male:
cryptorchidism
small testes

Head And Neck Face:
low anterior hairline

Growth Height:
severe postnatal growth retardation

Skeletal Skull:
postnatal microcephaly

Genitourinary External Genitalia Male:
hypoplastic scrotum
small penis

Neurologic Behavioral Psychiatric Manifestations:
autistic features (in some patients)

Clinical features from OMIM®:

615663 (Updated 20-May-2021)

Drugs & Therapeutics for Warburg Micro Syndrome 4

Search Clinical Trials , NIH Clinical Center for Warburg Micro Syndrome 4

Genetic Tests for Warburg Micro Syndrome 4

Genetic tests related to Warburg Micro Syndrome 4:

# Genetic test Affiliating Genes
1 Warburg Micro Syndrome 4 29 TBC1D20

Anatomical Context for Warburg Micro Syndrome 4

MalaCards organs/tissues related to Warburg Micro Syndrome 4:

40
Eye, Testes

Publications for Warburg Micro Syndrome 4

Articles related to Warburg Micro Syndrome 4:

# Title Authors PMID Year
1
Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. 6 57
24239381 2013
2
Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. 57
23420520 2013
3
New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. 57
20512159 2010
4
TBC1D20 mediates autophagy as a key regulator of autophagosome maturation. 61
27487390 2016
5
Targeted disruption of Tbc1d20 with zinc-finger nucleases causes cataracts and testicular abnormalities in mice. 61
25476608 2014

Variations for Warburg Micro Syndrome 4

ClinVar genetic disease variations for Warburg Micro Syndrome 4:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TBC1D20 NM_144628.4(TBC1D20):c.199C>T (p.Arg67Ter) SNV Pathogenic 100774 rs587777157 GRCh37: 20:428590-428590
GRCh38: 20:447946-447946
2 TBC1D20 NM_144628.4(TBC1D20):c.292C>T (p.Gln98Ter) SNV Pathogenic 100775 rs587777158 GRCh37: 20:425739-425739
GRCh38: 20:445095-445095
3 TBC1D20 NM_144628.4(TBC1D20):c.352_353del (p.Gln118fs) Deletion Pathogenic 100776 rs587777159 GRCh37: 20:422672-422673
GRCh38: 20:442028-442029
4 TBC1D20 NM_144628.4(TBC1D20):c.672G>A (p.Trp224Ter) SNV Pathogenic 100777 rs587777160 GRCh37: 20:420988-420988
GRCh38: 20:440344-440344
5 TBC1D20 NM_144628.2(TBC1D20):c.71-?_*1+?del Deletion Pathogenic 100778 GRCh37:
GRCh38: 20:435480-448074
6 TBC1D20 NM_144628.4(TBC1D20):c.932C>A (p.Ala311Asp) SNV Uncertain significance 976405 GRCh37: 20:419776-419776
GRCh38: 20:439132-439132
7 TBC1D20 NM_144628.4(TBC1D20):c.874A>G (p.Ile292Val) SNV Uncertain significance 1029160 GRCh37: 20:419834-419834
GRCh38: 20:439190-439190

Expression for Warburg Micro Syndrome 4

Search GEO for disease gene expression data for Warburg Micro Syndrome 4.

Pathways for Warburg Micro Syndrome 4

GO Terms for Warburg Micro Syndrome 4

Cellular components related to Warburg Micro Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.46 TBC1D23 RAB3GAP1 RAB2A RAB18
2 lipid droplet GO:0005811 9.32 RAB3GAP1 RAB18
3 endoplasmic reticulum-Golgi intermediate compartment membrane GO:0033116 9.26 TBC1D20 RAB2A
4 endoplasmic reticulum membrane GO:0005789 9.02 TBC1D20 RAB3GAP2 RAB3GAP1 RAB2A RAB18
5 endoplasmic reticulum tubular network GO:0071782 8.96 RAB3GAP1 RAB18

Biological processes related to Warburg Micro Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.58 TBC1D20 RAB3GAP2 RAB3GAP1
2 brain development GO:0007420 9.54 TBC1D23 RAB3GAP1 RAB18
3 Golgi organization GO:0007030 9.48 TBC1D20 RAB2A
4 regulation of GTPase activity GO:0043087 9.46 RAB3GAP2 RAB3GAP1
5 camera-type eye development GO:0043010 9.43 TBC1D20 RAB3GAP1
6 positive regulation of autophagosome assembly GO:2000786 9.32 RAB3GAP2 RAB3GAP1
7 positive regulation of endoplasmic reticulum tubular network organization GO:1903373 9.26 RAB3GAP2 RAB3GAP1
8 positive regulation of protein lipidation GO:1903061 9.16 RAB3GAP2 RAB3GAP1
9 establishment of protein localization to endoplasmic reticulum membrane GO:0097051 8.96 RAB3GAP2 RAB3GAP1
10 lipid droplet organization GO:0034389 8.8 TBC1D20 RAB3GAP1 RAB18

Molecular functions related to Warburg Micro Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GDP binding GO:0019003 9.16 RAB2A RAB18
2 small GTPase binding GO:0031267 9.13 TBC1D20 RAB3GAP2 RAB3GAP1
3 GTPase activator activity GO:0005096 8.8 TBC1D20 RAB3GAP2 RAB3GAP1

Sources for Warburg Micro Syndrome 4

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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