NADK2

Chr 5AR

NAD kinase 2, mitochondrial

Also known as: C5orf33, DECRD, MNADK, NADKD1

NCBI Gene: 133686 ENSG00000152620 UniProt: Q4G0N4 OMIM: 615787

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.521 OMIM phenotype

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.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 142 VUS of 305 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.28 (0.16–0.52)

0≤0.351.4

Missense OE?0.60 (0.52–0.70)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 25.3Missense obs/exp: 124 / 206.8Syn Z: 0.40

ClinVar Variant Classifications

305 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS142

Likely Benign127

Benign29

Conflicting5

Pathogenic

Likely Pathogenic

142

VUS

127

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	1	0	0	0	1
VUS	9	123	8	2	142
Likely Benign	1	2	62	62	127
Benign	0	4	22	3	29
Conflicting	—				5
Total	11	129	93	67	305

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap NADK2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →