NADK2

NAD kinase 2, mitochondrial

Basic information

Region (hg38): 5:36192589-36242279

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

Links

ENSG00000152620 ∙ NCBI:133686 ∙ OMIM:615787 ∙ HGNC:26404 ∙ Uniprot:Q4G0N4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
2,4-dienoyl-CoA reductase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	24847004

ClinVar

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

• Progressive_encephalopathy_with_leukodystrophy_due_to_DECR_deficiency (191 variants)
• Inborn_genetic_diseases (57 variants)
• not_provided (35 variants)
• not_specified (17 variants)
• NADK2-related_disorder (7 variants)
• Bardet-Biedl_syndrome_10 (1 variants)

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. These statistics are base on transcript: NM_001085411.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	55	3	59
missense			109	3	4	116
nonsense		1	4			5
start loss			1			1
frameshift		1	4			5
splice donor/acceptor (+/-2bp)						0
Total	0	2	119	58	7

Highest pathogenic variant AF is 0.0000107167

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NADK2	protein_coding	protein_coding	ENST00000381937	12	49688

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0652	0.935	125732	0	8	125740	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	124	207	0.600	0.0000107	2807
Missense in Polyphen		33	80.949	0.40767		1007
Synonymous	0.402	67	71.3	0.939	0.00000342	877
Loss of Function	3.37	7	25.3	0.277	0.00000137	306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000909	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000367	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000677	0.0000653
Other	0.00	0.00

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

• 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_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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