Neurodegeneration with brain iron accumulation (NBIA) subtypes pathway (Homo sapiens)

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131416103Coenzyme A synthesisBPAN DiseaseFAHN DiseaseLegendSphingolipid metabolism PathwayPalmitoyl-CoA(R)-4'-phosphopantothenateL-cysteinesphingomyelinSPTLC13-DehydrosphinganinedihydrosphingosineD-pantetheine 4'-phosphateACACA(R)-pantothenatediphosphateceramideFA2HMECP2Coenzyme Adihydroxysphingolipids1,2-saturated fatty acid(2R)-2-hydroxy fatty acid anionL-serinedihydroceramideCOASYPANK2acetyl-CoAFe(II)-cytochrome b5malonyl-CoA3'-dephospho-CoAsphingolipidsN-[(R)-4'-Phosphopantothenoyl]-L-cysteineFe(III)-cytochrome b51197592612128111896PIK3C3ATG10WIPI2ATG7ATG14AKT1S1ATG13RB1CC1AMPKRHEBULK1ATG16L1ATG12BECN1DEPTORLC3ATG2ALKB1ATG7PIK3R4TSC1ATG5MLST8TSC2ATG12WIPI1ATG4WDR45MTORRPTORPtdIns3PATG101ATG3ATG12ATG12ATG5LC3LC3LC3COASYCoPAN DiseasePKAN DiseaseIronLipid MetabolismFe2+Enoplasmic reticulumLysosomePLA2G6PeroxisomePantothenateMitochondrionAutophagosomeDCAF17NucleusWDR45MyelinsynthesisMembrane remodellingPLA2G6C19orf12FA2HATP13A2GTPBP2COASYPANK2FTLSCPxCoACPFe3+Lysosome / autophagosome synthesisIron homeostasisLipid metabolism and/or membrane remodellingUnknown function4


Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term for 12 disease subtypes, all characterized by the build-up of iron within the brain. One of these subtypes is beta-propeller protein-associated neurodegeneration (BPAN) caused by a mutation in the WDR45 gene. This protein is involved in the autophagy pathway; the exact mechanism is still unknown. Other NBIA subtypes are PKAN, CoPAN, and FAHN. PKAN and CoPAN are involved in Coenzyme A synthesis within mitochondria and FAHN is found in myelin synthesis. Dysfunctioning of these pathways leads to a phenotype characterized by developmental delay and intellectual disabilities. Nevertheless, the exact relation between mutation and phenotype remains unknown.

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109208view14:28, 27 February 2020Marvin M2Connected line
107175view14:26, 17 September 2019MaintBotChEBI identifier normalization
105274view21:32, 25 July 2019KhanspersModified title
104795view06:57, 18 June 2019GMKeulenChanged background color of lipid metabolism.
104775view10:32, 13 June 2019GMKeulenAdded pathway node.
104774view10:16, 13 June 2019GMKeulenAdded CheBI identifiers, changed mim-interactions to arrows.
104766view17:09, 12 June 2019GMKeulenFixed interactions within the overview figure.
104762view15:59, 12 June 2019GMKeulenAdded ensembl IDs to geneproducts
104761view15:43, 12 June 2019GMKeulenChanged text lables to geneproducts within the overview figure.
104685view11:21, 11 June 2019GMKeulenAdded literature reference for mTOR ULK1 inhibition.
104618view11:03, 4 June 2019GMKeulenAdded annotation and literature reference to PANK2 reaction.
104387view12:56, 23 May 2019GMKeulenAdded colors
104385view12:46, 23 May 2019GMKeulenAdded literature reference to figure
104384view12:44, 23 May 2019GMKeulenChanged title
104383view12:42, 23 May 2019GMKeulenAdded legend to the figure and pathway
104382view11:15, 23 May 2019GMKeulenAdded overview of different NBIA subtypes
104378view16:57, 22 May 2019GMKeulenChanged arrows to diseases
104352view09:18, 20 May 2019GMKeulenChanged names in disease lables, Corrected FA2H reaction. Added lables to the green and blue boxes.
104283view12:34, 15 May 2019FehrhartOntology Term : 'neuron' added !
104281view12:29, 15 May 2019Fehrhartgraphical fix
104207view09:00, 10 May 2019GMKeulenModified description
104064view08:24, 1 May 2019GMKeulenadded L-cysteine and diphosphate to phosphopantothenate reaction
104057view14:22, 29 April 2019GMKeulenadded MECP2 and FA2H reaction
104054view10:50, 29 April 2019GMKeulenAdded enzymatic function of FA2H
104046view06:11, 27 April 2019EgonwReplaced a secondary ChEBI ID with its primary ID.
104045view12:59, 26 April 2019GMKeulenAdded metabolites, and disease FAHN
104044view12:09, 26 April 2019GMKeulenAdded rhea identifiers, annotated metabolites and added metabolites
104041view09:08, 26 April 2019GMKeulenOntology Term : 'disease pathway' added !
104040view09:08, 26 April 2019GMKeulenOntology Term : 'neurodegeneration with brain iron accumulation' added !
104008view14:22, 25 April 2019GMKeulenchanged layout
104005view12:46, 25 April 2019GMKeulenAnnotated metabolites with chebi identifier, linked diseases to OMIM and connected reactions.
104004view12:15, 25 April 2019GMKeulenconnected AMPK
103998view08:11, 25 April 2019GMKeulenModified description
103997view08:08, 25 April 2019DeSlConnected PANK2
103996view07:58, 25 April 2019DeSlConnected CoPAN
103995view07:54, 25 April 2019DeSlChanged characters for Muller and Urbe
103994view07:51, 25 April 2019DeSlchanged character to beta.
103993view07:41, 25 April 2019DeSlConnected AMPK to group, layout change
103989view12:50, 24 April 2019GMKeulenNew pathway

External references


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NameTypeDatabase referenceComment
(2R)-2-hydroxy fatty acid anionMetaboliteCHEBI:76177 (ChEBI)
(R)-4'- phosphopantothenateMetaboliteCHEBI:10986 (ChEBI)
(R)-pantothenateMetaboliteCHEBI:29032 (ChEBI)
1,2-saturated fatty acidMetaboliteCHEBI:83955 (ChEBI)
3'-dephospho -CoAMetaboliteCHEBI:57328 (ChEBI)
3-DehydrosphinganineMetaboliteCHEBI:17862 (ChEBI)
ACACAGeneProductENSG00000278540 (Ensembl)
AKT1S1GeneProductENSG00000204673 (Ensembl)
AMPKGeneProductENSG00000132356 (Ensembl)
ATG101GeneProductENSG00000123395 (Ensembl)
ATG10GeneProductENSG00000152348 (Ensembl)
ATG12GeneProductENSG00000145782 (Ensembl)
ATG13GeneProductENSG00000175224 (Ensembl)
ATG14GeneProductENSG00000126775 (Ensembl)
ATG16L1GeneProductENSG00000085978 (Ensembl)
ATG2AGeneProductENSG00000110046 (Ensembl)
ATG3GeneProductENSG00000144848 (Ensembl)
ATG4GeneProductENSG00000101844 (Ensembl)
ATG5GeneProductENSG00000057663 (Ensembl)
ATG7GeneProductENSG00000197548 (Ensembl)
ATP13A2GeneProductENSG00000159363 (Ensembl)
BECN1GeneProductENSG00000126581 (Ensembl)
C19orf12GeneProductENSG00000131943 (Ensembl)
COASYGeneProductENSG00000068120 (Ensembl)
CPGeneProductENSG00000047457 (Ensembl)
Coenzyme AMetaboliteCHEBI:57287 (ChEBI)
D-pantetheine 4'-phosphateMetaboliteCHEBI:61723 (ChEBI)
DCAF17GeneProductENSG00000115827 (Ensembl)
DEPTORGeneProductENSG00000155792 (Ensembl)
FA2HGeneProductENSG00000103089 (Ensembl)
FTLGeneProductENSG00000087086 (Ensembl)
Fe(II)-cytochrome b5MetaboliteCHEBI:29033 (ChEBI)
Fe(III)-cytochrome b5MetaboliteCHEBI:29034 (ChEBI)
GTPBP2GeneProductENSG00000172432 (Ensembl)
L-cysteineMetaboliteCHEBI:35235 (ChEBI)
L-serineMetaboliteCHEBI:33384 (ChEBI)
LC3GeneProductENSG00000101460 (Ensembl)
LKB1GeneProductENSG00000118046 (Ensembl)
MECP2GeneProductENSG00000169057 (Ensembl)
MLST8GeneProductENSG00000167965 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
N-[(R)-4'-Phospho pantothenoyl]-L-cysteineMetaboliteCHEBI:59458 (ChEBI)
PANK2GeneProductENSG00000125779 (Ensembl)
PIK3C3GeneProductENSG00000078142 (Ensembl)
PIK3R4GeneProductENSG00000196455 (Ensembl)
PLA2G6GeneProductENSG00000184381 (Ensembl)
Palmitoyl-CoAMetaboliteCHEBI:57379 (ChEBI)
PtdIns3PMetaboliteCHEBI:26034 (ChEBI)
RB1CC1GeneProductENSG00000023287 (Ensembl)
RHEBGeneProductENSG00000106615 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)
SCPxGeneProductENSG00000116171 (Ensembl)
SPTLC1GeneProductENSG00000090054 (Ensembl)
Sphingolipid metabolism PathwayPathwayWP4142 (WikiPathways)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
ULK1GeneProductENSG00000177169 (Ensembl)
WDR45GeneProductENSG00000196998 (Ensembl)
WIPI1GeneProductENSG00000070540 (Ensembl)
WIPI2GeneProductENSG00000157954 (Ensembl)
acetyl-CoAMetaboliteCHEBI:57288 (ChEBI)
ceramideMetaboliteCHEBI:17761 (ChEBI)
dihydroceramideMetaboliteCHEBI:139048 (ChEBI)
dihydrosphingosineMetabolite46878428 (PubChem-compound)
diphosphateMetaboliteCHEBI:33019 (ChEBI)
malonyl-CoAMetaboliteCHEBI:57384 (ChEBI)
sphingolipidsMetaboliteCHEBI:26739 (ChEBI)
sphingomyelinMetaboliteCHEBI:17636 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(R)-4'- phosphopantothenateN-[(R)-4'-Phospho pantothenoyl]-L-cysteinemim-conversion25156 (Rhea)
(R)-pantothenate(R)-4'- phosphopantothenatemim-conversion16374 (Rhea) Phosphorylation
1,2-saturated fatty acid(2R)-2-hydroxy fatty acid anionmim-conversion38855 (Rhea)
3'-dephospho -CoACoenzyme Amim-conversion18246 (Rhea)
D-pantetheine 4'-phosphate3'-dephospho -CoAmim-conversion19802 (Rhea)
N-[(R)-4'-Phospho pantothenoyl]-L-cysteineD-pantetheine 4'-phosphatemim-conversion16793 (Rhea)
Palmitoyl-CoAL-serine14761 (Rhea)
acetyl-CoAmalonyl-CoAmim-conversion18818 (Rhea)
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