GDAP1 ganglioside induced differentiation associated protein 1 [Homo sapiens] - Gene

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Summary

Official Symbol: GDAP1provided by HGNC
Official Full Name: ganglioside induced differentiation associated protein 1provided by HGNC
Primary source: HGNC:15968
See related: Ensembl:ENSG00000104381; HPRD:05963; MIM:606598; Vega:OTTHUMG00000164509
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CMT4; CMT4A; CMTRIA
Summary: 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]

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Genomic context

Location :: 8q21.11

Sequence :: Chromosome: 8; NC_000008.10 (75262618..75279345)

See GDAP1 in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Patients of type 4 Charcot-Marie-Tooth disease showed reduced GDAP1 levels, GHS concentration and mitochondrial membrane potential.
Title: Charcot-Marie-Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential.
Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase in Saccharomyces cerevisiae fis1 gene-defective cells
Title: Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase in Saccharomyces cerevisiae fis1 gene-defective cells.
we report two recessive intermediate Charcot-Marie-Tooth (RI-CMT) patients with GDAP1 missense mutations
Title: Two recessive intermediate Charcot-Marie-Tooth patients with GDAP1 mutations.
We show that patients with dominant GDAP1 mutations may display clear axonal Charcot-Marie-Tooth disease
Title: Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.
Clinical outcome of Charcot-Marie-Tooth disease caused by mutations in the GDAP1 gene cannot be predicted solely on the basis of genetic results (missense/nonsense mutations).
Title: A new missense GDAP1 mutation disturbing targeting to the mitochondrial membrane causes a severe form of AR-CMT2C disease.
An p.R120W mutation has been identified in GDAP1 causing autosomal dominant Charcot-Marie-Tooth disease with a wide clinical profile.
Title: Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease.
This review provide that Mitochondrial dysfunction and pathophysiology of Charcot-Marie-Tooth disease involving GDAP1 mutations.
Title: Mitochondrial dysfunction and pathophysiology of Charcot-Marie-Tooth disease involving GDAP1 mutations.
A mutations frquency of 27% in the GST domain of GDAP1 in the dominant form of axonal Charcot Marie Tooth type 2K was observed.
Title: The GST domain of GDAP1 is a frequent target of mutations in the dominant form of axonal Charcot Marie Tooth type 2K.
Charcot-Marie-Tooth type 4C4 (CMT4C4) phenotype associated with the third recurrent GDAP1 mutation having a common origin in European population was characterized.
Title: L239F founder mutation in GDAP1 is associated with a mild Charcot-Marie-Tooth type 4C4 (CMT4C4) phenotype.
different cellular mechanisms that disturb mitochondrial dynamics underlie the similar clinical manifestations caused by GDAP1 mutations, depending on the mode of inheritance
Title: GDAP1 mutations differ in their effects on mitochondrial dynamics and apoptosis depending on the mode of inheritance.

Submit: New GeneRIF Correction See all (31)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide association study identifies protein quantitative trait loci (pQTLs).

Charcot-Marie-Tooth neuropathy type 4A (CMT4A), an aggressive form of hereditary motor and sensory neuropathy (HMSN), is confined to the peripheral nervous system, and typically affects the lower extremities earlier and more severely than the upper extremities. As the neuropathy progresses, the distal upper extremities also become severely affected. Even proximal muscles can become weak. Age at onset is from infancy to early childhood. In most cases, disease progression causes disabilities within the first or second decade of life. At the end of the second decade, most individuals are wheelchair bound. Disease progression varies considerably even within the same family. The neuropathy can be either of the demyelinating type with reduced nerve conduction velocities or the axonal type with normal nerve conduction velocities. Vocal cord paresis is common. Intelligence is normal. Life expectancy is usually not affected, but on occasion may be reduced because of secondary complications.

Diagnosis Testing

Diagnosis of CMT4A is based on clinical findings and confirmed by molecular genetic testing of GDAP1, the only gene known to be associated with CMT4A. Such testing is clinically available.

Genetic Counseling

CMT4A is usually inherited in an autosomal recessive manner. The asymptomatic parents of an affected individual are obligate heterozygotes (carriers) and therefore carry one mutant allele. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible for families in which the disease-causing mutations have been identified.

References

PMID: 20301711

Charcot-Marie-Tooth disease, recessive intermediate, A

MIM: 608340

Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project.

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:119934	BioGRID:119230	FIS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119934	BioGRID:128444	TUBB	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:119934	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

RH18434 (e-PCR)
- UniSTS:27659

MARC_17537-17538:1017261090:1 (e-PCR)
- UniSTS:268335

A004Y31 (e-PCR)
- UniSTS:83002

RH12692 (e-PCR)
- UniSTS:29032

RH91794 (e-PCR)
- UniSTS:86207

GDAP1_9778 (e-PCR)
- UniSTS:468435

Genotypes

See GDAP1 SNP Geneview Report
See GDAP1 SNP Genotype Report
See GDAP1 SNP Variation Viewer Report

Homology

Homologs of the GDAP1 gene: The GDAP1 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, A.thaliana, and rice.
Map Viewer (Mouse, Rat)

Gene Ontology Provided by GOA

Process	Evidence Code	Pubs
response to retinoic acid	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info

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General protein information

Preferred Names: ganglioside-induced differentiation-associated protein 1

Names: ganglioside-induced differentiation-associated protein 1; Charcot-Marie-Tooth neuropathy 4A; ganglioside differentiation associated protein 1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008787.2 RefSeqGene

Range

34254..50981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001040875.2 → NP_001035808.1 ganglioside-induced differentiation-associated protein 1 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate in-frame exon and uses an alternate splice site in the 5' coding region, and uses a downstream start codon, compared to variant 1. Isoform b has a shorter N-terminus, compared to isoform a.

Source sequence(s)

AB551556, BC024939, DB505741

Consensus CDS

CCDS47877.1

UniProtKB/TrEMBL

E7FJF3

UniProtKB/Swiss-Prot

Q8TB36

Related

ENSP00000417006, OTTHUMP00000226875, ENST00000434412, OTTHUMT00000379062

Conserved Domains (3) summary

TIGR01262
Location:2 – 76
Blast Score: 96

maiA; maleylacetoacetate isomerase

cd10303
Location:111 – 221
Blast Score: 569

GST_C_GDAP1; C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1

cl00388
Location:1 – 30
Blast Score: 150

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
NM_018972.2 → NP_061845.2 ganglioside-induced differentiation-associated protein 1 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest variant and encodes the longer isoform (a).

Source sequence(s)

AC103952, DB505741, Y17849

Consensus CDS

CCDS34911.1

UniProtKB/Swiss-Prot

Q8TB36

Related

ENSP00000220822, OTTHUMP00000226874, ENST00000220822, OTTHUMT00000379061

Conserved Domains (3) summary

COG0625
Location:26 – 292
Blast Score: 190

Gst; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]

cd03052
Location:26 – 98
Blast Score: 377

GST_N_GDAP1; GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have ...

cd10303
Location:179 – 289
Blast Score: 566

GST_C_GDAP1; C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1

RNA

NR_046346.1 RNA Sequence

Description

Transcript Variant: This variant (3) uses an alternate splice junction at the 3' end of an exon compared to variant 1, that causes a frameshift. The putative ORF is overlapped by a uORF with a strong Kozak signal, so it is not likely that this transcript is translated.

Source sequence(s)

AB551556, AK295594, DB505741

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p5 Primary Assembly

Range

75262618..75279345

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

70753599..70770326

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC103952.5 (22093..38785)	None
genomic	CH471068.1	EAW87032.1
		EAW87033.1
mRNA	AB551556.1	BAJ65577.1
mRNA	AB551557.1	BAJ65578.1
mRNA	AB551558.1	BAJ65579.1
mRNA	AK292572.1	BAF85261.1
mRNA	AK295594.1	BAG58484.1
mRNA	AL110252.1	None
mRNA	BC024939.1	AAH24939.1
mRNA	BC035450.1	None
mRNA	BC036496.1	None
mRNA	DB505741.1	None
mRNA	Y17849.1	CAA76892.1