NADK2

Chr 5AR

NAD kinase 2, mitochondrial

Also known as: C5orf33, DECRD, MNADK, NADKD1

The protein is a mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+), using either ATP or inorganic polyphosphate as the phosphoryl donor. Mutations cause 2,4-dienoyl-CoA reductase deficiency, which follows autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.52), suggesting some tolerance to complete gene loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.521 OMIM phenotype
Clinical SummaryNADK2
🧬
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.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 144 VUS of 327 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.065
Z-score 3.37
OE 0.28 (0.160.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.05Z-score
OE missense 0.60 (0.520.70)
124 obs / 206.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.160.52)
00.351.4
Missense OE0.60 (0.520.70)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 7 / 25.3Missense obs/exp: 124 / 206.8Syn Z: 0.40

ClinVar Variant Classifications

327 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic4
VUS144
Likely Benign127
Benign29
Conflicting5
18
Pathogenic
4
Likely Pathogenic
144
VUS
127
Likely Benign
29
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
1
0
3
0
4
VUS
9
122
11
2
144
Likely Benign
1
2
62
62
127
Benign
0
4
22
3
29
Conflicting
5
Total1112811667327

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

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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