NAXD

Chr 13AR

NAD(P)HX dehydratase

Also known as: CARKD, LP3298, PEBEL2

NCBI Gene: 55739ENSG00000213995UniProt: Q8IW45OMIM: 615910

NAXD encodes a mitochondrial enzyme that catalyzes ATP-dependent dehydration of NAD(P)HX to repair damaged NAD(P)H cofactors. Mutations cause autosomal recessive progressive encephalopathy with early onset, characterized by brain edema and leukoencephalopathy. The gene shows tolerance to loss-of-function variants (pLI 0.007, LOEUF 0.8), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical Summary— NAXD
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
129 unique Pathogenic / Likely Pathogenic· 85 VUS of 322 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.007
Z-score 2.12
OE 0.41 (0.22–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.89Z-score
OE missense 0.84 (0.75–0.94)
203 obs / 242.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.22–0.80)
0≤0.351.4
Missense OE0.84 (0.75–0.94)
0≤0.61.4
Synonymous OE1.15
0≤1.21.6
LoF obs/exp: 6 / 14.8Missense obs/exp: 203 / 242.2Syn Z: -1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNAXD-related neurodegenerative disorder exacerbated by febrile illnessesLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.5464th %ile
LOF
0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

322 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic120
Likely Pathogenic9
VUS85
Likely Benign72
Benign17
Conflicting6
120
Pathogenic
9
Likely Pathogenic
85
VUS
72
Likely Benign
17
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
2
112
0
120
Likely Pathogenic
6
1
2
0
9
VUS
4
61
20
0
85
Likely Benign
0
8
18
46
72
Benign
1
4
8
4
17
Conflicting
—6
Total177616050309

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

View in ClinVar →

Protein Context — Lollipop Plot

NAXD · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients