Human Gene GDAP1 (uc003yah.3) Description and Page Index
  Description: Homo sapiens ganglioside induced differentiation associated protein 1 (GDAP1), transcript variant 1, mRNA.
RefSeq Summary (NM_018972): This gene encodes a member of the ganglioside-induced differentiation-associated protein family, which may play a role in a signal transduction pathway during neuronal development. Mutations in this gene have been associated with various forms of Charcot-Marie-Tooth Disease and neuropathy. Two transcript variants encoding different isoforms and a noncoding variant have been identified for this gene. [provided by RefSeq, Feb 2012].
Transcript (Including UTRs)
   Position: hg19 chr8:75,262,618-75,279,335 Size: 16,718 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg19 chr8:75,262,697-75,276,602 Size: 13,906 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesGeneReviewsModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:75,262,618-75,279,335)mRNA (may differ from genome)Protein (358 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: GDAP1_HUMAN
DESCRIPTION: RecName: Full=Ganglioside-induced differentiation-associated protein 1; Short=GDAP1;
FUNCTION: Regulates the mitochondrial network by promoting mitochondrial fission.
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass membrane protein. Cytoplasm (By similarity).
TISSUE SPECIFICITY: Highly expressed in whole brain and spinal cord. Predominant expression in central tissues of the nervous system not only in neurons but also in Schwann cells.
DISEASE: Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease type 4A (CMT4A) [MIM:214400]. CMT4A is a form of Charcot- Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. Autosomal recessive forms of demyelinating Charcot-Marie- Tooth disease are by convention designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence.
DISEASE: Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease axonal recessive with vocal cord paresis (CMT2RV) [MIM:607706]. CMT2RV is a form of Charcot-Marie-Tooth disease characterized by the association of axonal neuropathy with vocal cord paresis.
DISEASE: Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease type 2K (CMT2K) [MIM:607831]. CMT2K is an axonal form of Charcot-Marie-Tooth disease. Axonal CMT neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2K onset is in early childhood (younger than 3 years). This phenotype is characterized by foot deformities, kyphoscoliosis, distal limb muscle weakness and atrophy, areflexia, and diminished sensation in the lower limbs. Weakness in the upper limbs is observed in the first decade, with clawing of the fingers. Inheritance can be autosomal dominant or recessive.
DISEASE: Defects in GDAP1 are the cause of Charcot-Marie-Tooth disease recessive intermediate type A (CMTRIA) [MIM:608340]. CMTRIA is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
MISCELLANEOUS: Does not have glutathione transferase activity, although it appears to be structurally related to other cytosolic glutathione S-transferases (GST).
SIMILARITY: Belongs to the GST superfamily.
SIMILARITY: Contains 1 GST C-terminal domain.
SIMILARITY: Contains 1 GST N-terminal domain.
WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; URL="http://www.molgen.ua.ac.be/CMTMutations/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GDAP1";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GDAP1
CDC HuGE Published Literature: GDAP1
Positive Disease Associations: Arthritis, Rheumatoid , Body Weight , Body Weights and Measures , Myocardial Infarction , Myoglobin , protein quantitative trait loci , Waist Circumference , waist circumference traits
Related Studies:
  1. Arthritis, Rheumatoid
    J Wang et al. The pharmacogenomics journal 2012, Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis., The pharmacogenomics journal. [PubMed 22491018]
  2. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: GDAP1
Diseases sorted by gene-association score: charcot-marie-tooth disease, type 4a* (1678), charcot-marie-tooth disease, axonal, type 2k* (1568), charcot-marie-tooth disease, recessive intermediate, a* (1550), charcot-marie-tooth disease, axonal, with vocal cord paresis* (1231), charcot-marie-tooth disease type 2g* (500), gdap1-related intermediate charcot-marie-tooth neuropathy* (500), sensory peripheral neuropathy* (425), charcot-marie-tooth disease type 2k* (419), polyneuropathy* (406), isolated hyperckemia* (400), charcot-marie-tooth disease* (337), creatine phosphokinase, elevated serum* (283), roussy-levy syndrome* (107), charcot-marie-tooth neuropathy type 2h/2k* (100), neuropathy, congenital hypomyelinating* (38), charcot-marie-tooth disease, axonal, type 2h* (29), tooth disease (23), neuropathy (18), charcot-marie-tooth neuropathy (15), charcot-marie-tooth disease, type 4f (12), axonal neuropathy (9), charcot-marie-tooth disease, type 4b3 (8), charcot-marie-tooth disease, type 4b1 (8), charcot-marie-tooth disease, type 4b2 (8), charcot-marie-tooth disease, type 4c (7), charcot-marie-tooth disease, type 4d (7), hereditary motor and sensory neuropathy, type iic (7), charcot-marie-tooth disease, type 2b2 (7), charcot-marie-tooth disease, type 2b1 (7), charcot-marie-tooth disease, type 4j (6), dejerine-sottas disease (6), neuropathy, recurrent, with pressure palsies (6), charcot-marie-tooth disease, type 1e (6), charcot-marie-tooth disease, type 1a (5), peripheral nervous system disease (5), myoclonic epilepsy associated with ragged-red fibers (3), mitochondrial complex i deficiency (2), charcot-marie-tooth disease, type 2e (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 32.18 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 359.06 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -32.2079-0.408 Picture PostScript Text
3' UTR -732.842733-0.268 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR010987 - Glutathione-S-Trfase_C-like
IPR004045 - Glutathione_S-Trfase_N
IPR017933 - Glutathione_S_Trfase/Cl_chnl_C
IPR012336 - Thioredoxin-like_fold

Pfam Domains:
PF00043 - Glutathione S-transferase, C-terminal domain
PF02798 - Glutathione S-transferase, N-terminal domain
PF13409 - Glutathione S-transferase, N-terminal domain
PF13410 - Glutathione S-transferase, C-terminal domain
PF13417 - Glutathione S-transferase, N-terminal domain
PF14497 - Glutathione S-transferase, C-terminal domain

SCOP Domains:
47616 - Glutathione S-transferase (GST), C-terminal domain
52833 - Thioredoxin-like

ModBase Predicted Comparative 3D Structure on Q8TB36
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserNo orthologNo ortholog
Gene Details  Gene Details  
Gene Sorter  Gene Sorter  
  EnsemblFlyBase  
  Protein SequenceProtein Sequence  
  AlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004364 glutathione transferase activity

Biological Process:
GO:0000266 mitochondrial fission
GO:0006626 protein targeting to mitochondrion
GO:0006749 glutathione metabolic process
GO:0008053 mitochondrial fusion
GO:0032526 response to retinoic acid
GO:0071305 cellular response to vitamin D

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005829 cytosol
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031307 integral component of mitochondrial outer membrane


-  Descriptions from all associated GenBank mRNAs
  AB551556 - Homo sapiens GDAP1 mRNA for ganglioside differentiation associated protein 1, complete cds, c179g mutation.
AB551557 - Homo sapiens GDAP1 mRNA for ganglioside differentiation associated protein 1, complete cds, a756t mutation.
AB551558 - Homo sapiens GDAP1 mRNA for truncated ganglioside differentiation associated protein 1, complete cds, 2-bp deletion.
BC024939 - Homo sapiens ganglioside-induced differentiation-associated protein 1, mRNA (cDNA clone MGC:18012 IMAGE:3923335), complete cds.
BC035450 - Homo sapiens, clone IMAGE:3923326, mRNA.
AK292572 - Homo sapiens cDNA FLJ75809 complete cds, highly similar to Homo sapiens ganglioside-induced differentiation-associated protein 1 (GDAP1), mRNA.
AK295594 - Homo sapiens cDNA FLJ60563 complete cds, highly similar to Ganglioside-induceddifferentiation-associated protein 1.
Y17849 - Homo sapiens mRNA for ganglioside-induced differentiation associated protein 1.
KJ894015 - Synthetic construct Homo sapiens clone ccsbBroadEn_03409 GDAP1 gene, encodes complete protein.
KR709602 - Synthetic construct Homo sapiens clone CCSBHm_00003908 GDAP1 (GDAP1) mRNA, encodes complete protein.
KR709603 - Synthetic construct Homo sapiens clone CCSBHm_00003915 GDAP1 (GDAP1) mRNA, encodes complete protein.
KR709604 - Synthetic construct Homo sapiens clone CCSBHm_00003923 GDAP1 (GDAP1) mRNA, encodes complete protein.
KR709605 - Synthetic construct Homo sapiens clone CCSBHm_00003928 GDAP1 (GDAP1) mRNA, encodes complete protein.
BC036496 - Homo sapiens cDNA clone IMAGE:5263960.
AL110252 - Homo sapiens mRNA; cDNA DKFZp566A1046 (from clone DKFZp566A1046).

-  Other Names for This Gene
  Alternate Gene Symbols: GDAP1_HUMAN, NM_018972, NP_001035808, Q8TB36
UCSC ID: uc003yah.3
RefSeq Accession: NM_018972
Protein: Q8TB36 (aka GDAP1_HUMAN or GDP1_HUMAN)
CCDS: CCDS34911.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GDAP1:
cmt (Charcot-Marie-Tooth Hereditary Neuropathy Overview)
cmt-4a (GDAP1-Related Hereditary Motor and Sensory Neuropathy)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_018972.2
exon count: 6CDS single in 3' UTR: no RNA size: 3899
ORF size: 1077CDS single in intron: no Alignment % ID: 99.97
txCdsPredict score: 2354.00frame shift in genome: no % Coverage: 99.74
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.