NBIA2B
MCID: NRD009
MIFTS: 45

Neurodegeneration with Brain Iron Accumulation 2b (NBIA2B)

Categories: Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Neurodegeneration with Brain Iron Accumulation 2b

MalaCards integrated aliases for Neurodegeneration with Brain Iron Accumulation 2b:

Name: Neurodegeneration with Brain Iron Accumulation 2b 57 12 72 29 13 6 15
Nbia2b 57 12 72
Neurodegeneration with Brain Iron Accumulation, Pla2g6-Related 57 12
Neuroaxonal Dystrophy, Atypical 57 12
Karak Syndrome 72 70
Neurodegeneration with Brain Iron Accumulation Pla2g6-Related 72
Neurodegeneration, with Brain Iron Accumulation, Type 2b 39
Neurodegeneration with Brain Iron Accumulation 2 70
Atypical Neuroaxonal Dystrophy 72

Characteristics:

OMIM®:

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

Miscellaneous:
variable phenotype
progressive disorder
childhood onset (average 4 to 6 years)
allelic disorder to infantile neuroaxonal dystrophy


HPO:

31
neurodegeneration with brain iron accumulation 2b:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


Classifications:



Summaries for Neurodegeneration with Brain Iron Accumulation 2b

UniProtKB/Swiss-Prot : 72 Neurodegeneration with brain iron accumulation 2B: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive extrapyramidal dysfunction leading to rigidity, dystonia, dysarthria and sensorimotor impairment.

MalaCards based summary : Neurodegeneration with Brain Iron Accumulation 2b, also known as nbia2b, is related to neurodegeneration with brain iron accumulation 2a and dystonia, and has symptoms including seizures, dysdiadochokinesis and gait ataxia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 2b is PLA2G6 (Phospholipase A2 Group VI), and among its related pathways/superpathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include brain, eye and cerebellum, and related phenotypes are spasticity and nystagmus

Disease Ontology : 12 A neurodegeneration with brain iron accumulation that has material basis in autosomal recessive inheritance of mutation in the PLA2G6 gene on chromosome 22q13.1.

More information from OMIM: 610217 PS234200

Related Diseases for Neurodegeneration with Brain Iron Accumulation 2b

Diseases in the Neurodegeneration with Brain Iron Accumulation family:

Neurodegeneration with Brain Iron Accumulation 1 Neurodegeneration with Brain Iron Accumulation 2a
Neurodegeneration with Brain Iron Accumulation 5 Neurodegeneration with Brain Iron Accumulation 3
Neurodegeneration with Brain Iron Accumulation 2b Neurodegeneration with Brain Iron Accumulation 4
Neurodegeneration with Brain Iron Accumulation 6 Neurodegeneration with Brain Iron Accumulation 7
Neurodegeneration with Brain Iron Accumulation 8

Diseases related to Neurodegeneration with Brain Iron Accumulation 2b via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 32)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration with brain iron accumulation 2a 29.3 PNPLA8 PNPLA2 PLA2G6 PANK2 PANK1 FTL
2 dystonia 28.1 PLA2G6 PANK2 FTL FA2H DCAF17 COASY
3 neuroaxonal dystrophy 27.7 PNPLA8 PNPLA2 PLA2G6 PANK2 PANK1 FTL
4 karak syndrome 11.5
5 congenital disorder of glycosylation, type ip 10.1 PANK2 C19orf12
6 iron metabolism disease 10.1 PANK2 FTL
7 alacrima, achalasia, and mental retardation syndrome 10.0
8 parkinsonism 10.0
9 spastic paraplegia 43, autosomal recessive 9.9 PLA2G6 FA2H C19orf12
10 barth syndrome 9.8 PNPLA8 PLA2G6
11 hemochromatosis, type 1 9.8 PANK2 PANK1 FTL
12 complex hereditary spastic paraplegia 9.8 FA2H ATP13A2
13 choreoacanthocytosis 9.8 PANK2 PANK1 FTL C19orf12
14 spinocerebellar ataxia, autosomal recessive 24 9.7 FA2H ATP13A2
15 paraplegia 9.7 FA2H C19orf12 ATP13A2
16 fanconi anemia, complementation group d2 9.7 FA2H COASY
17 choreatic disease 9.5 PANK2 FTL C19orf12 ATP13A2
18 hereditary spastic paraplegia 9.5 PLA2G6 FA2H C19orf12 ATP13A2
19 neurodegeneration with brain iron accumulation 4 9.4 PLA2G6 PANK2 FTL FA2H DCAF17 C19orf12
20 oromandibular dystonia 9.4 PLA2G6 PANK2 FA2H C19orf12 ATP13A2
21 parkinson disease 15, autosomal recessive early-onset 9.4 PLA2G6 PANK2 FA2H C19orf12 ATP13A2
22 early-onset parkinson's disease 9.4 PLA2G6 PANK2 FA2H C19orf12 ATP13A2
23 movement disease 9.0 PLA2G6 PANK2 PANK1 FTL FA2H C19orf12
24 spastic paraplegia 35, autosomal recessive 8.9 PLA2G6 PANK2 FA2H DCAF17 COASY C19orf12
25 kufor-rakeb syndrome 8.7 PLA2G6 PANK2 PANK1 FA2H DCAF17 COASY
26 neurodegeneration with brain iron accumulation 5 8.7 PLA2G6 PANK2 PANK1 FA2H DCAF17 COASY
27 neurodegeneration with brain iron accumulation 3 8.5 PLA2G6 PANK2 PANK1 FTL FA2H DCAF17
28 aceruloplasminemia 8.5 PLA2G6 PANK2 PANK1 FTL FA2H DCAF17
29 acrocephalopolysyndactyly type iii 8.5 PLA2G6 PANK2 PANK1 FTL FA2H DCAF17
30 neurodegeneration with brain iron accumulation 6 8.4 PLA2G6 PANK3 PANK2 PANK1 FA2H DCAF17
31 neurodegeneration with brain iron accumulation 1 8.2 PLA2G6 PANK3 PANK2 PANK1 FTL FA2H
32 neurodegeneration with brain iron accumulation 8.1 PNPLA2 PLA2G6 PANK3 PANK2 PANK1 FTL

Graphical network of the top 20 diseases related to Neurodegeneration with Brain Iron Accumulation 2b:



Diseases related to Neurodegeneration with Brain Iron Accumulation 2b

Symptoms & Phenotypes for Neurodegeneration with Brain Iron Accumulation 2b

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation 2b:

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 HP:0001257
2 nystagmus 31 HP:0000639
3 emotional lability 31 HP:0000712
4 dysarthria 31 HP:0001260
5 dysphagia 31 HP:0002015
6 chorea 31 HP:0002072
7 delayed speech and language development 31 HP:0000750
8 optic atrophy 31 HP:0000648
9 hypertonia 31 HP:0001276
10 dysmetria 31 HP:0001310
11 mental deterioration 31 HP:0001268
12 dystonia 31 HP:0001332
13 dysdiadochokinesis 31 HP:0002075
14 gait ataxia 31 HP:0002066
15 babinski sign 31 HP:0003487
16 feeding difficulties 31 HP:0011968
17 cerebellar atrophy 31 HP:0001272
18 cerebral atrophy 31 HP:0002059
19 hyperactivity 31 HP:0000752
20 intention tremor 31 HP:0002080
21 impulsivity 31 HP:0100710
22 short attention span 31 HP:0000736
23 talipes calcaneovalgus 31 HP:0001884
24 bradykinesia 31 HP:0002067
25 neurofibrillary tangles 31 HP:0002185
26 lewy bodies 31 HP:0100315
27 neurodegeneration 31 HP:0002180
28 impaired smooth pursuit 31 HP:0007772
29 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
spasticity
dysarthria
hypertonia
dysmetria
more
Neurologic Behavioral Psychiatric Manifestations:
emotional lability
hyperactivity
impulsivity
autistic features
poor attention span
more
Skeletal Feet:
pes calcaneovarus

Head And Neck Eyes:
nystagmus
impaired smooth pursuit
abnormal saccades
optic atrophy (67%)

Abdomen Gastrointestinal:
dysphagia
feeding difficulties

Clinical features from OMIM®:

610217 (Updated 20-May-2021)

UMLS symptoms related to Neurodegeneration with Brain Iron Accumulation 2b:


seizures; dysdiadochokinesis; gait ataxia; bradykinesia; action tremor; muscle spasticity; cerebellar ataxia

MGI Mouse Phenotypes related to Neurodegeneration with Brain Iron Accumulation 2b:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.81 ATP13A2 COASY FA2H FTL PANK1 PANK2
2 cellular MP:0005384 9.56 ATP13A2 COASY DCAF17 PANK1 PANK2 PLA2G6
3 homeostasis/metabolism MP:0005376 9.32 ATP13A2 COASY FA2H FTL PANK1 PANK2

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation 2b

Search Clinical Trials , NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation 2b

Genetic Tests for Neurodegeneration with Brain Iron Accumulation 2b

Genetic tests related to Neurodegeneration with Brain Iron Accumulation 2b:

# Genetic test Affiliating Genes
1 Neurodegeneration with Brain Iron Accumulation 2b 29 PLA2G6

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 2b

MalaCards organs/tissues related to Neurodegeneration with Brain Iron Accumulation 2b:

40
Brain, Eye, Cerebellum

Publications for Neurodegeneration with Brain Iron Accumulation 2b

Articles related to Neurodegeneration with Brain Iron Accumulation 2b:

(show all 15)
# Title Authors PMID Year
1
Neurodegeneration associated with genetic defects in phospholipase A(2). 57 6
18799783 2008
2
Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). 6 57
18443314 2008
3
PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. 57 6
16783378 2006
4
The structure of iPLA2β reveals dimeric active sites and suggests mechanisms of regulation and localization. 6
29472584 2018
5
PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes. 6
30619057 2018
6
Child Neurology: Two sisters with dystonia and regression: PLA2G6-associated neurodegeneration. 6
27378808 2016
7
Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration. 6
26668131 2016
8
PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease. 6
24745848 2014
9
Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. 6
20619503 2012
10
Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. 6
20886109 2010
11
Clinical and genetic delineation of neurodegeneration with brain iron accumulation. 57
18981035 2009
12
PLA2G6-Associated Neurodegeneration 6
20301718 2008
13
Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. 57
17142829 2007
14
Karak syndrome: a novel degenerative disorder of the basal ganglia and cerebellum. 57
12843330 2003
15
PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia. 61
30302010 2019

Variations for Neurodegeneration with Brain Iron Accumulation 2b

ClinVar genetic disease variations for Neurodegeneration with Brain Iron Accumulation 2b:

6 (show all 29)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PLA2G6 NM_003560.4(PLA2G6):c.1349-2A>G SNV Pathogenic 211909 rs797045888 GRCh37: 22:38522458-38522458
GRCh38: 22:38126451-38126451
2 PLA2G6 NM_003560.4(PLA2G6):c.1880-9del Deletion Pathogenic 623393 rs1569243771 GRCh37: 22:38511697-38511697
GRCh38: 22:38115690-38115690
3 PLA2G6 NM_003560.4(PLA2G6):c.319del (p.Leu107fs) Deletion Pathogenic 984695 GRCh37: 22:38541551-38541551
GRCh38: 22:38145544-38145544
4 PLA2G6 NM_003560.4(PLA2G6):c.1442T>A (p.Leu481Gln) SNV Pathogenic 159731 rs587784330 GRCh37: 22:38519251-38519251
GRCh38: 22:38123244-38123244
5 PLA2G6 NM_003560.4(PLA2G6):c.2070_2072del (p.Val691del) Deletion Pathogenic 6198 rs587784343 GRCh37: 22:38509624-38509626
GRCh38: 22:38113617-38113619
6 PLA2G6 NM_003560.4(PLA2G6):c.2370T>G (p.Tyr790Ter) SNV Pathogenic 6195 rs121908680 GRCh37: 22:38508219-38508219
GRCh38: 22:38112212-38112212
7 PLA2G6 NM_003560.4(PLA2G6):c.1894C>T (p.Arg632Trp) SNV Pathogenic 6199 rs121908683 GRCh37: 22:38511674-38511674
GRCh38: 22:38115667-38115667
8 PLA2G6 NM_003560.4(PLA2G6):c.1933C>T (p.Arg645Ter) SNV Pathogenic 1028628 GRCh37: 22:38511635-38511635
GRCh38: 22:38115628-38115628
9 PLA2G6 NM_003560.4(PLA2G6):c.1634A>C (p.Lys545Thr) SNV Pathogenic 6196 rs121908681 GRCh37: 22:38516874-38516874
GRCh38: 22:38120867-38120867
10 PLA2G6 NM_003560.4(PLA2G6):c.2370_2371del (p.Tyr790_Glu791delinsTer) Deletion Pathogenic 6201 rs587784353 GRCh37: 22:38508218-38508219
GRCh38: 22:38112211-38112212
11 PLA2G6 NM_003560.4(PLA2G6):c.238G>A (p.Ala80Thr) SNV Pathogenic 6202 rs121908685 GRCh37: 22:38541632-38541632
GRCh38: 22:38145625-38145625
12 PLA2G6 NM_003560.4(PLA2G6):c.2222G>A (p.Arg741Gln) SNV Pathogenic 6203 rs121908686 GRCh37: 22:38508565-38508565
GRCh38: 22:38112558-38112558
13 PLA2G6 NM_003560.4(PLA2G6):c.2370T>G (p.Tyr790Ter) SNV Pathogenic 6195 rs121908680 GRCh37: 22:38508219-38508219
GRCh38: 22:38112212-38112212
14 PLA2G6 NM_003560.4(PLA2G6):c.1799G>A (p.Arg600Gln) SNV Pathogenic/Likely pathogenic 159748 rs149712244 GRCh37: 22:38512162-38512162
GRCh38: 22:38116155-38116155
15 PLA2G6 NM_003560.4(PLA2G6):c.2233C>T (p.Arg745Trp) SNV Likely pathogenic 159762 rs587784350 GRCh37: 22:38508554-38508554
GRCh38: 22:38112547-38112547
16 PLA2G6 NM_003560.4(PLA2G6):c.1976A>G (p.Asn659Ser) SNV Likely pathogenic 436319 rs1555978219 GRCh37: 22:38511592-38511592
GRCh38: 22:38115585-38115585
17 PLA2G6 NM_003560.4(PLA2G6):c.2239C>T (p.Arg747Trp) SNV Likely pathogenic 6204 rs121908687 GRCh37: 22:38508548-38508548
GRCh38: 22:38112541-38112541
18 PLA2G6 NM_003560.4(PLA2G6):c.1427+1G>A SNV Likely pathogenic 437465 rs750939090 GRCh37: 22:38522377-38522377
GRCh38: 22:38126370-38126370
19 PLA2G6 NM_003560.4(PLA2G6):c.945_947dup (p.Ala316dup) Duplication Likely pathogenic 211911 rs797045889 GRCh37: 22:38528967-38528968
GRCh38: 22:38132960-38132961
20 PLA2G6 NM_003560.4(PLA2G6):c.1742+2T>G SNV Likely pathogenic 973564 GRCh37: 22:38516764-38516764
GRCh38: 22:38120757-38120757
21 PLA2G6 NM_003560.4(PLA2G6):c.1506G>C (p.Lys502Asn) SNV Likely pathogenic 436320 rs1555988382 GRCh37: 22:38519187-38519187
GRCh38: 22:38123180-38123180
22 PLA2G6 NM_003560.4(PLA2G6):c.238G>A (p.Ala80Thr) SNV Uncertain significance 6202 rs121908685 GRCh37: 22:38541632-38541632
GRCh38: 22:38145625-38145625
23 PLA2G6 NM_003560.4(PLA2G6):c.16C>T (p.Arg6Cys) SNV Uncertain significance 493345 rs143250889 GRCh37: 22:38565418-38565418
GRCh38: 22:38169411-38169411
24 PLA2G6 NM_003560.4(PLA2G6):c.1615G>A (p.Gly539Ser) SNV Uncertain significance 159740 rs143826762 GRCh37: 22:38516893-38516893
GRCh38: 22:38120886-38120886
25 PLA2G6 NM_003560.4(PLA2G6):c.898G>A (p.Ala300Thr) SNV Uncertain significance 235257 rs528966598 GRCh37: 22:38529017-38529017
GRCh38: 22:38133010-38133010
26 PLA2G6 NM_003560.4(PLA2G6):c.416G>A (p.Arg139His) SNV Uncertain significance 426191 rs141825182 GRCh37: 22:38541454-38541454
GRCh38: 22:38145447-38145447
27 PLA2G6 NM_003560.4(PLA2G6):c.101C>T (p.Ser34Leu) SNV Uncertain significance 341649 rs147948449 GRCh37: 22:38565333-38565333
GRCh38: 22:38169326-38169326
28 PLA2G6 NM_003560.4(PLA2G6):c.91G>A (p.Asp31Asn) SNV Uncertain significance 341650 rs150024227 GRCh37: 22:38565343-38565343
GRCh38: 22:38169336-38169336
29 PLA2G6 NM_003560.4(PLA2G6):c.2152G>A (p.Ala718Thr) SNV Uncertain significance 973857 GRCh37: 22:38509544-38509544
GRCh38: 22:38113537-38113537

UniProtKB/Swiss-Prot genetic disease variations for Neurodegeneration with Brain Iron Accumulation 2b:

72
# Symbol AA change Variation ID SNP ID
1 PLA2G6 p.Lys545Thr VAR_029372 rs121908681
2 PLA2G6 p.Arg632Trp VAR_029373 rs121908683

Expression for Neurodegeneration with Brain Iron Accumulation 2b

Search GEO for disease gene expression data for Neurodegeneration with Brain Iron Accumulation 2b.

Pathways for Neurodegeneration with Brain Iron Accumulation 2b

GO Terms for Neurodegeneration with Brain Iron Accumulation 2b

Biological processes related to Neurodegeneration with Brain Iron Accumulation 2b according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.76 PANK3 PANK2 PANK1 COASY
2 lipid metabolic process GO:0006629 9.73 PNPLA8 PNPLA2 PLA2G6 FA2H
3 lipid catabolic process GO:0016042 9.5 PNPLA8 PNPLA2 PLA2G6
4 cellular iron ion homeostasis GO:0006879 9.48 FTL ATP13A2
5 phosphatidylcholine acyl-chain remodeling GO:0036151 9.4 PNPLA8 PLA2G6
6 phosphatidylethanolamine acyl-chain remodeling GO:0036152 9.37 PNPLA8 PLA2G6
7 lipid homeostasis GO:0055088 9.33 PNPLA8 PNPLA2 ATP13A2
8 phosphatidylcholine catabolic process GO:0034638 9.26 PNPLA8 PLA2G6
9 phosphatidylethanolamine catabolic process GO:0046338 8.96 PNPLA8 PLA2G6
10 coenzyme A biosynthetic process GO:0015937 8.92 PANK3 PANK2 PANK1 COASY

Molecular functions related to Neurodegeneration with Brain Iron Accumulation 2b according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.8 PNPLA8 PANK3 PANK2 PANK1 COASY ATP13A2
2 kinase activity GO:0016301 9.71 PANK3 PANK2 PANK1 COASY
3 lysophospholipase activity GO:0004622 9.37 PNPLA8 PLA2G6
4 phosphatidyl phospholipase B activity GO:0102545 9.26 PNPLA8 PLA2G6
5 calcium-independent phospholipase A2 activity GO:0047499 9.16 PNPLA8 PLA2G6
6 acetyl-CoA binding GO:1905502 8.96 PANK3 PANK1
7 pantothenate kinase activity GO:0004594 8.8 PANK3 PANK2 PANK1

Sources for Neurodegeneration with Brain Iron Accumulation 2b

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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