NADK2

NAD kinase 2, mitochondrial

Basic information

Region (hg38): 5:36192589-36242279

Previous symbols: [ "C5orf33", "NADKD1" ]

Links

ENSG00000152620NCBI:133686OMIM:615787HGNC:26404Uniprot:Q4G0N4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • progressive encephalopathy with leukodystrophy due to DECR deficiency (Strong), mode of inheritance: AR
  • progressive encephalopathy with leukodystrophy due to DECR deficiency (Moderate), mode of inheritance: AR
  • progressive encephalopathy with leukodystrophy due to DECR deficiency (Supportive), mode of inheritance: AR
  • progressive encephalopathy with leukodystrophy due to DECR deficiency (Limited), mode of inheritance: AR
  • progressive encephalopathy with leukodystrophy due to DECR deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
2,4-dienoyl-CoA reductase deficiencyARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Neurologic24847004

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NADK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NADK2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
3
clinvar
43
clinvar
3
clinvar
49
missense
75
clinvar
1
clinvar
3
clinvar
79
nonsense
1
clinvar
2
clinvar
3
start loss
3
clinvar
3
frameshift
1
clinvar
4
clinvar
5
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
7
6
1
14
non coding
6
clinvar
45
clinvar
19
clinvar
70
Total 0 2 94 90 25

Variants in NADK2

This is a list of pathogenic ClinVar variants found in the NADK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
5-36195163-G-A Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jun 29, 2023)1523201
5-36195168-A-C Likely benign (Jan 01, 2024)3026372
5-36195177-T-A Inborn genetic diseases Uncertain significance (Mar 02, 2023)2469266
5-36195196-G-A Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Nov 08, 2022)1427734
5-36195203-T-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jan 11, 2024)959061
5-36195225-A-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Likely benign (Feb 11, 2023)2738933
5-36195237-A-G Progressive encephalopathy with leukodystrophy due to DECR deficiency Likely benign (Sep 26, 2023)2875080
5-36195238-T-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jan 30, 2023)2832870
5-36195244-A-G Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jan 24, 2023)2912678
5-36195248-T-C Progressive encephalopathy with leukodystrophy due to DECR deficiency • NADK2-related disorder • Inborn genetic diseases Conflicting classifications of pathogenicity (Jan 29, 2024)798229
5-36195252-G-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Likely benign (Aug 23, 2022)1634430
5-36195255-A-G Likely benign (Jul 20, 2018)764749
5-36195263-A-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jun 20, 2023)3013040
5-36195271-C-T Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jun 14, 2022)1990508
5-36195288-C-A not specified Likely benign (Apr 21, 2017)508264
5-36195346-A-C Likely benign (May 13, 2021)1321582
5-36195346-A-G Benign (Jun 29, 2018)1235193
5-36197529-G-C Progressive encephalopathy with leukodystrophy due to DECR deficiency Likely benign (Feb 26, 2023)2740993
5-36197535-G-A Progressive encephalopathy with leukodystrophy due to DECR deficiency • Inborn genetic diseases Uncertain significance (Jul 21, 2022)1036792
5-36197555-A-G Progressive encephalopathy with leukodystrophy due to DECR deficiency Likely benign (Mar 30, 2021)1639639
5-36197556-C-T Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Apr 09, 2023)2722590
5-36197563-G-A Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Jun 03, 2023)2187785
5-36197579-T-C Likely benign (Mar 01, 2024)1695123
5-36197582-A-G not specified Likely benign (Jul 11, 2017)518098
5-36197598-C-T Progressive encephalopathy with leukodystrophy due to DECR deficiency Uncertain significance (Mar 24, 2021)1503907

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NADK2protein_codingprotein_codingENST00000381937 1249688
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.06520.935125732081257400.0000318
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.051242070.6000.00001072807
Missense in Polyphen3380.9490.407671007
Synonymous0.4026771.30.9390.00000342877
Loss of Function3.37725.30.2770.00000137306

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00009090.0000905
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003670.0000352
Middle Eastern0.000.00
South Asian0.00006770.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. {ECO:0000269|PubMed:23212377}.;
Pathway
Nicotinate and nicotinamide metabolism - Homo sapiens (human);Metabolism;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Intolerance Scores

loftool
rvis_EVS
0.53
rvis_percentile_EVS
80.73

Haploinsufficiency Scores

pHI
0.156
hipred
Y
hipred_score
0.673
ghis
0.448

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nadk2
Phenotype
liver/biliary system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); limbs/digits/tail phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype;

Gene ontology

Biological process
NADP biosynthetic process;phosphorylation;NAD metabolic process
Cellular component
mitochondrion;mitochondrial matrix
Molecular function
NAD+ kinase activity;ATP binding;protein homodimerization activity