LIS3
MCID: LSS009
MIFTS: 39

Lissencephaly 3 (LIS3)

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

Aliases & Classifications for Lissencephaly 3

MalaCards integrated aliases for Lissencephaly 3:

Name: Lissencephaly 3 57 12 72 29 13 6 70
Lis3 57 12 72
Type Iii Lissencephaly 29 6
Lissencephaly Due to Tuba1a Mutation 58
Lissencephaly, Type 3 39
Lissencephaly Type 3 58

Characteristics:

Orphanet epidemiological data:

58
lissencephaly due to tuba1a mutation
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation (in most patients)


HPO:

31
lissencephaly 3:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0112232
OMIM® 57 611603
OMIM Phenotypic Series 57 PS607432
MeSH 44 D054082
ICD10 via Orphanet 33 Q04.3
UMLS via Orphanet 71 C1969029
MedGen 41 C1969029
UMLS 70 C1969029

Summaries for Lissencephaly 3

UniProtKB/Swiss-Prot : 72 Lissencephaly 3: A classic type lissencephaly associated with psychomotor retardation and seizures. Features include agyria or pachygyria or laminar heterotopia, severe mental retardation, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem.

MalaCards based summary : Lissencephaly 3, also known as lis3, is related to lissencephaly and lissencephaly with cerebellar hypoplasia, and has symptoms including seizures and ataxia. An important gene associated with Lissencephaly 3 is TUBA1A (Tubulin Alpha 1a). Affiliated tissues include brain, and related phenotypes are agenesis of corpus callosum and ataxia

Disease Ontology : 12 A lissencephaly characterized by brain malformations, microcephaly, developmental delay and epilepsy that has material basis in heterozygous mutation in TUBA1A on chromosome 12q13.12.

More information from OMIM: 611603 PS607432

Related Diseases for Lissencephaly 3

Graphical network of the top 20 diseases related to Lissencephaly 3:



Diseases related to Lissencephaly 3

Symptoms & Phenotypes for Lissencephaly 3

Human phenotypes related to Lissencephaly 3:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 HP:0001274
2 ataxia 31 HP:0001251
3 microcephaly 31 HP:0000252
4 spastic tetraplegia 31 HP:0002510
5 intellectual disability, severe 31 HP:0010864
6 motor delay 31 HP:0001270
7 ventriculomegaly 31 HP:0002119
8 polymicrogyria 31 HP:0002126
9 pachygyria 31 HP:0001302
10 hypoplasia of the corpus callosum 31 HP:0002079
11 gray matter heterotopia 31 HP:0002282
12 cerebellar vermis hypoplasia 31 HP:0001320
13 generalized hypotonia 31 HP:0001290
14 hypoplasia of the brainstem 31 HP:0002365
15 agyria 31 HP:0031882
16 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
spastic tetraplegia
polymicrogyria
lissencephaly
more
Head And Neck Head:
microcephaly

Clinical features from OMIM®:

611603 (Updated 05-Apr-2021)

UMLS symptoms related to Lissencephaly 3:


seizures; ataxia

GenomeRNAi Phenotypes related to Lissencephaly 3 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-114 9.23 AIPL1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-115 9.23 TUBA1A
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-134 9.23 AIPL1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-140 9.23 TUBA1A
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.23 TUBA1A
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 9.23 TUBA1A
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.23 AIPL1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-76 9.23 TUBA1A

MGI Mouse Phenotypes related to Lissencephaly 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.13 CENPJ NKX2-5 TUBA1A
2 nervous system MP:0003631 8.92 AIPL1 CENPJ NKX2-5 TUBA1A

Drugs & Therapeutics for Lissencephaly 3

Search Clinical Trials , NIH Clinical Center for Lissencephaly 3

Genetic Tests for Lissencephaly 3

Genetic tests related to Lissencephaly 3:

# Genetic test Affiliating Genes
1 Lissencephaly 3 29 TUBA1A
2 Type Iii Lissencephaly 29

Anatomical Context for Lissencephaly 3

MalaCards organs/tissues related to Lissencephaly 3:

40
Brain

Publications for Lissencephaly 3

Articles related to Lissencephaly 3:

(show all 15)
# Title Authors PMID Year
1
TUBA1A mutations: from isolated lissencephaly to familial polymicrogyria. 6 57
21403111 2011
2
TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. 57 6
20466733 2010
3
Refining the phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly. 6 57
18954413 2008
4
Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations. 6 57
18728072 2008
5
Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A). 6 57
17584854 2007
6
Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. 6 57
17218254 2007
7
Comprehensive genomic analysis of patients with disorders of cerebral cortical development. 6
29706646 2018
8
Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation. 6
30087272 2018
9
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
10
Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. 57
25059107 2014
11
The wide spectrum of tubulinopathies: what are the key features for the diagnosis? 6
24860126 2014
12
Expanding the spectrum of TUBA1A-related cortical dysgenesis to Polymicrogyria. 57
22948023 2013
13
Disease-associated mutations in TUBA1A result in a spectrum of defects in the tubulin folding and heterodimer assembly pathway. 6
20603323 2010
14
Iterative ACORN as a high throughput tool in structural genomics. 61
17133764 2006
15
Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. 61
7751941 1995

Variations for Lissencephaly 3

ClinVar genetic disease variations for Lissencephaly 3:

6 (show top 50) (show all 73)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TUBA1A NM_006009.4(TUBA1A):c.562A>C (p.Ile188Leu) SNV Pathogenic 7072 rs137853045 GRCh37: 12:49579587-49579587
GRCh38: 12:49185804-49185804
2 TUBA1A NM_006009.4(TUBA1A):c.787C>A (p.Pro263Thr) SNV Pathogenic 7073 rs137853046 GRCh37: 12:49579362-49579362
GRCh38: 12:49185579-49185579
3 TUBA1A NM_006009.4(TUBA1A):c.1256C>T (p.Ser419Leu) SNV Pathogenic 7074 rs137853047 GRCh37: 12:49578893-49578893
GRCh38: 12:49185110-49185110
4 TUBA1A NM_006009.4(TUBA1A):c.1190T>C (p.Leu397Pro) SNV Pathogenic 7075 rs137853048 GRCh37: 12:49578959-49578959
GRCh38: 12:49185176-49185176
5 TUBA1A NM_006009.4(TUBA1A):c.13A>C (p.Ile5Leu) SNV Pathogenic 30268 rs387906840 GRCh37: 12:49580607-49580607
GRCh38: 12:49186824-49186824
6 TUBA1A NM_006009.4(TUBA1A):c.1205G>T (p.Arg402Leu) SNV Pathogenic 160147 rs137853044 GRCh37: 12:49578944-49578944
GRCh38: 12:49185161-49185161
7 TUBA1A NM_006009.4(TUBA1A):c.481T>G (p.Tyr161Asp) SNV Pathogenic 160158 rs587784488 GRCh37: 12:49579668-49579668
GRCh38: 12:49185885-49185885
8 TUBA1A NM_006009.4(TUBA1A):c.1224C>A (p.Tyr408Ter) SNV Pathogenic 209200 rs753719501 GRCh37: 12:49578925-49578925
GRCh38: 12:49185142-49185142
9 TUBA1A NM_006009.4(TUBA1A):c.167C>T (p.Thr56Met) SNV Pathogenic 625513 rs1565627727 GRCh37: 12:49580453-49580453
GRCh38: 12:49186670-49186670
10 TUBA1A NM_006009.4(TUBA1A):c.701T>G (p.Ile234Ser) SNV Pathogenic 976320 GRCh37: 12:49579448-49579448
GRCh38: 12:49185665-49185665
11 TUBA1A NM_006009.4(TUBA1A):c.545T>C (p.Val182Ala) SNV Pathogenic 977324 GRCh37: 12:49579604-49579604
GRCh38: 12:49185821-49185821
12 TUBA1A NM_006009.4(TUBA1A):c.1169G>A (p.Arg390His) SNV Pathogenic 488628 rs1064796460 GRCh37: 12:49578980-49578980
GRCh38: 12:49185197-49185197
13 TUBA1A NM_006009.4(TUBA1A):c.1264C>T (p.Arg422Cys) SNV Pathogenic 7076 rs137853049 GRCh37: 12:49578885-49578885
GRCh38: 12:49185102-49185102
14 TUBA1A NM_006009.4(TUBA1A):c.1226T>C (p.Val409Ala) SNV Pathogenic 208490 rs797045005 GRCh37: 12:49578923-49578923
GRCh38: 12:49185140-49185140
15 TUBA1A NM_006009.4(TUBA1A):c.652G>A (p.Asp218Asn) SNV Pathogenic 372561 rs1057517858 GRCh37: 12:49579497-49579497
GRCh38: 12:49185714-49185714
16 CENPJ NM_018451.5(CENPJ):c.1132C>T (p.Arg378Ter) SNV Pathogenic 503611 rs201111299 GRCh37: 13:25481044-25481044
GRCh38: 13:24906906-24906906
17 TUBA1A NM_006009.4(TUBA1A):c.790C>T (p.Arg264Cys) SNV Pathogenic 7070 rs137853043 GRCh37: 12:49579359-49579359
GRCh38: 12:49185576-49185576
18 TUBA1A NM_006009.4(TUBA1A):c.1205G>A (p.Arg402His) SNV Pathogenic 7071 rs137853044 GRCh37: 12:49578944-49578944
GRCh38: 12:49185161-49185161
19 TUBA1A NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His) SNV Pathogenic 7077 rs137853050 GRCh37: 12:49578884-49578884
GRCh38: 12:49185101-49185101
20 TUBA1A NM_006009.4(TUBA1A):c.1204C>T (p.Arg402Cys) SNV Pathogenic 160146 rs587784483 GRCh37: 12:49578945-49578945
GRCh38: 12:49185162-49185162
21 CENPJ NM_018451.5(CENPJ):c.289dup (p.Thr97fs) Duplication Pathogenic 279750 rs759188041 GRCh37: 13:25486874-25486875
GRCh38: 13:24912736-24912737
22 TUBA1A NM_006009.4(TUBA1A):c.986A>G (p.Asn329Ser) SNV Pathogenic 160167 rs587784495 GRCh37: 12:49579163-49579163
GRCh38: 12:49185380-49185380
23 TUBA1A NM_006009.4(TUBA1A):c.958C>T (p.Arg320Cys) SNV Pathogenic 864866 GRCh37: 12:49579191-49579191
GRCh38: 12:49185408-49185408
24 TUBA1A NM_006009.4(TUBA1A):c.641G>A (p.Arg214His) SNV Pathogenic/Likely pathogenic 372542 rs1057517843 GRCh37: 12:49579508-49579508
GRCh38: 12:49185725-49185725
25 TUBA1A NM_006009.4(TUBA1A):c.1169G>C (p.Arg390Pro) SNV Pathogenic/Likely pathogenic 423490 rs1064796460 GRCh37: 12:49578980-49578980
GRCh38: 12:49185197-49185197
26 TUBA1A NM_006009.4(TUBA1A):c.5G>A (p.Arg2His) SNV Pathogenic/Likely pathogenic 160161 rs587784491 GRCh37: 12:49580615-49580615
GRCh38: 12:49186832-49186832
27 TUBA1A NM_006009.4(TUBA1A):c.521C>T (p.Ala174Val) SNV Likely pathogenic 160159 rs587784489 GRCh37: 12:49579628-49579628
GRCh38: 12:49185845-49185845
28 TUBA1A NM_006009.4(TUBA1A):c.1105G>A (p.Ala369Thr) SNV Likely pathogenic 212488 rs797046071 GRCh37: 12:49579044-49579044
GRCh38: 12:49185261-49185261
29 TUBA1A NM_006009.4(TUBA1A):c.652G>A (p.Asp218Asn) SNV Likely pathogenic 372561 rs1057517858 GRCh37: 12:49579497-49579497
GRCh38: 12:49185714-49185714
30 TUBA1A NM_006009.4(TUBA1A):c.1156G>A (p.Glu386Lys) SNV Likely pathogenic 1028470 GRCh37: 12:49578993-49578993
GRCh38: 12:49185210-49185210
31 TUBA1A NM_006009.4(TUBA1A):c.703G>C (p.Val235Leu) SNV Likely pathogenic 1028472 GRCh37: 12:49579446-49579446
GRCh38: 12:49185663-49185663
32 TUBA1A NM_006009.4(TUBA1A):c.217A>G (p.Thr73Ala) SNV Likely pathogenic 689469 rs1592260393 GRCh37: 12:49580403-49580403
GRCh38: 12:49186620-49186620
33 TUBA1A NM_006009.4(TUBA1A):c.995T>C (p.Ile332Thr) SNV Likely pathogenic 160169 rs587784497 GRCh37: 12:49579154-49579154
GRCh38: 12:49185371-49185371
34 TUBA1A NM_006009.4(TUBA1A):c.1084G>C (p.Val362Leu) SNV Likely pathogenic 978812 GRCh37: 12:49579065-49579065
GRCh38: 12:49185282-49185282
35 TUBA1A NM_006009.4(TUBA1A):c.180G>T (p.Lys60Asn) SNV Likely pathogenic 632599 rs1565627707 GRCh37: 12:49580440-49580440
GRCh38: 12:49186657-49186657
36 TUBA1A NM_006009.4(TUBA1A):c.196_206delinsACGTGTGTCGC (p.Val66_Asp69delinsThrCysValAla) Indel Likely pathogenic 977831 GRCh37: 12:49580414-49580424
GRCh38: 12:49186631-49186641
37 TUBA1A NM_006009.4(TUBA1A):c.1049G>T (p.Gly350Val) SNV Likely pathogenic 873446 GRCh37: 12:49579100-49579100
GRCh38: 12:49185317-49185317
38 TUBA1A NM_006009.4(TUBA1A):c.47T>C (p.Ile16Thr) SNV Likely pathogenic 873454 GRCh37: 12:49580573-49580573
GRCh38: 12:49186790-49186790
39 TUBA1A NM_006009.4(TUBA1A):c.74G>A (p.Cys25Tyr) SNV Likely pathogenic 800951 rs1565627777 GRCh37: 12:49580546-49580546
GRCh38: 12:49186763-49186763
40 TUBA1A NM_006009.4(TUBA1A):c.1261G>A (p.Ala421Thr) SNV Likely pathogenic 802856 rs1592259391 GRCh37: 12:49578888-49578888
GRCh38: 12:49185105-49185105
41 TUBA1A NM_006009.4(TUBA1A):c.598T>C (p.Cys200Arg) SNV Likely pathogenic 864864 GRCh37: 12:49579551-49579551
GRCh38: 12:49185768-49185768
42 TUBA1A NM_006009.4(TUBA1A):c.746A>G (p.Asn249Ser) SNV Likely pathogenic 864865 GRCh37: 12:49579403-49579403
GRCh38: 12:49185620-49185620
43 TUBA1A NM_006009.4(TUBA1A):c.808G>T (p.Ala270Ser) SNV Likely pathogenic 160164 rs587784494 GRCh37: 12:49579341-49579341
GRCh38: 12:49185558-49185558
44 TUBA1A NM_006009.4(TUBA1A):c.962G>A (p.Gly321Asp) SNV Likely pathogenic 620024 GRCh37: 12:49579187-49579187
GRCh38: 12:49185404-49185404
45 TUBA1A NM_006009.4(TUBA1A):c.269A>G (p.Glu90Gly) SNV Likely pathogenic 212491 rs797046072 GRCh37: 12:49580199-49580199
GRCh38: 12:49186416-49186416
46 TUBA1A NM_006009.4(TUBA1A):c.970G>C (p.Val324Leu) SNV Likely pathogenic 212494 rs797046073 GRCh37: 12:49579179-49579179
GRCh38: 12:49185396-49185396
47 TUBA1A NM_006009.4(TUBA1A):c.352G>A (p.Val118Met) SNV Likely pathogenic 217023 rs863224938 GRCh37: 12:49580116-49580116
GRCh38: 12:49186333-49186333
48 TUBA1A NM_006009.4(TUBA1A):c.1144A>G (p.Thr382Ala) SNV Likely pathogenic 437121 rs1555162294 GRCh37: 12:49579005-49579005
GRCh38: 12:49185222-49185222
49 TUBA1A NM_006009.4(TUBA1A):c.368G>A (p.Arg123His) SNV Likely pathogenic 437122 rs1555162456 GRCh37: 12:49580100-49580100
GRCh38: 12:49186317-49186317
50 TUBA1A NM_006009.4(TUBA1A):c.1304T>C (p.Val435Ala) SNV Likely pathogenic 437120 rs1555162242 GRCh37: 12:49578845-49578845
GRCh38: 12:49185062-49185062

UniProtKB/Swiss-Prot genetic disease variations for Lissencephaly 3:

72
# Symbol AA change Variation ID SNP ID
1 TUBA1A p.Ile188Leu VAR_039332 rs137853045
2 TUBA1A p.Pro263Thr VAR_039333 rs137853046
3 TUBA1A p.Arg264Cys VAR_039334 rs137853043
4 TUBA1A p.Leu286Phe VAR_039335
5 TUBA1A p.Arg402Cys VAR_039336 rs587784483
6 TUBA1A p.Arg402His VAR_039337 rs137853044
7 TUBA1A p.Ser419Leu VAR_039338 rs137853047
8 TUBA1A p.Arg402Leu VAR_078711 rs137853044

Expression for Lissencephaly 3

Search GEO for disease gene expression data for Lissencephaly 3.

Pathways for Lissencephaly 3

GO Terms for Lissencephaly 3

Biological processes related to Lissencephaly 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G2/M transition of mitotic cell cycle GO:0000086 9.16 TUBA1A CENPJ
2 ciliary basal body-plasma membrane docking GO:0097711 8.96 TUBA1A CENPJ
3 regulation of G2/M transition of mitotic cell cycle GO:0010389 8.62 TUBA1A CENPJ

Molecular functions related to Lissencephaly 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein domain specific binding GO:0019904 8.62 TUBA1A CENPJ

Sources for Lissencephaly 3

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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