GDAP1

Chr 8ADAR

ganglioside induced differentiation associated protein 1

Also known as: CMT4, CMT4A, CMTRIA

NCBI Gene: 54332ENSG00000104381UniProt: Q8TB36

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]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2KMIM #607831
ADAR
Charcot-Marie-Tooth disease, axonal, with vocal cord paresisMIM #607706
AR
Charcot-Marie-Tooth disease, recessive intermediate, AMIM #608340
AR
Charcot-Marie-Tooth disease, type 4AMIM #214400
AR
669
ClinVar variants
80
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GDAP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
80 Pathogenic / Likely Pathogenic· 237 VUS of 669 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 1.03
OE 0.74 (0.49–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.00Z-score
OE missense 0.80 (0.69–0.91)
150 obs / 188.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.49–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.69–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 14 / 18.8Missense obs/exp: 150 / 188.7Syn Z: -0.51

ClinVar Variant Classifications

669 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic35
VUS237
Likely Benign125
Benign26
Conflicting22
45
Pathogenic
35
Likely Pathogenic
237
VUS
125
Likely Benign
26
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
3
24
0
45
Likely Pathogenic
16
11
8
0
35
VUS
3
171
63
0
237
Likely Benign
0
0
54
71
125
Benign
0
0
25
1
26
Conflicting
—22
Total3718517472490

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GDAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, axonal, type 2K

MIM #607831

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Charcot-Marie-Tooth disease, axonal, with vocal cord paresis

MIM #607706

Molecular basis of disorder known

Autosomal recessive

Charcot-Marie-Tooth disease, recessive intermediate, A

MIM #608340

Molecular basis of disorder known

Autosomal recessive

Charcot-Marie-Tooth disease, type 4A

MIM #214400

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited mitochondrial neuropathies.
Finsterer J·J Neurol Sci
2011Review
Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease.
González-Sánchez P et al.·Int J Mol Sci
2019Review
[Charcot-Marie-Tooth disease].
Birouk N·Presse Med
2009
Variants in mitochondrial disease genes are common causes of inherited peripheral neuropathies.
Ferreira T et al.·J Neurol
2024
Mitochondrial dysfunction and pathophysiology of Charcot-Marie-Tooth disease involving GDAP1 mutations.
Cassereau J et al.·Exp Neurol
2011Review
GDAP1-Related Charcot-Marie-Tooth Disease: Axonal or Demyelinating Subtype? Autosomal Recessive or Autosomal Dominant Inheritance?
Ravanbod M et al.·J Peripher Nerv Syst
2025
A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?
Kamińska J et al.·Int J Mol Sci
2024Review
Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain.
Sivera R et al.·Sci Rep
2017
Differential effects of Mendelian GDAP1 clinical variants on mitochondria-lysosome membrane contacts sites.
Cantarero L et al.·Biol Open
2023
Genetic and clinical profile of 15 Chinese families with GDAP1-related Charcot-Marie-Tooth disease and identification of H256R as a frequent mutation.
Li Z et al.·J Peripher Nerv Syst
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools