NADK2

Chr 5AR

NAD kinase 2, mitochondrial

Also known as: C5orf33, DECRD, MNADK, NADKD1

NCBI Gene: 133686ENSG00000152620UniProt: Q4G0N4

This gene encodes a mitochondrial kinase that catalyzes the phosphorylation of NAD to yield NADP. Mutations in this gene result in 2,4-dienoyl-CoA reductase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

2,4-dienoyl-CoA reductase deficiencyMIM #616034
AR
0
ClinVar variants
0
Pathogenic / LP
0.07
pLI score
0
Active trials
Clinical Summary— NADK2
🧬
Gene-Disease Validity (ClinGen)
progressive encephalopathy with leukodystrophy due to DECR deficiency · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.52LOEUF
pLI 0.065
Z-score 3.37
OE 0.28 (0.16–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.05Z-score
OE missense 0.60 (0.52–0.70)
124 obs / 206.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.28 (0.16–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.52–0.70)
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.0.94
0≤1.21.6
LoF obs/exp: 7 / 25.3Missense obs/exp: 124 / 206.8Syn Z: 0.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NADK2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NADK2-related dienoyl-CoA reductase deficiency with hyperlysinemia

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

2,4-dienoyl-CoA reductase deficiency

MIM #616034

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant.
Pomerantz DJ et al.·Am J Med Genet A
2018Review
Molecular mechanism of melatonin-mediated mitophagy regulating proline production to ameliorate skin aging.
Quan T et al.·Exp Gerontol
2025Functional
The Undiagnosed Diseases Network (UDN) Solves Ocular Syndromic Diagnostic Dilemmas.
Tinker RJ et al.·Am J Ophthalmol
2025Case report
Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient.
Tort F et al.·Pediatrics
2016Case report
Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.
Houten SM et al.·Hum Mol Genet
2014Case report
The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand.
Kim H et al.·Mol Metab
2022
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