NADK2
Basic information
Region (hg38): 5:36192589-36242279
Previous symbols: [ "C5orf33", "NADKD1" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
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 | 43 | 49 | ||||
missense | 75 | 79 | ||||
nonsense | 3 | |||||
start loss | 3 | |||||
frameshift | 5 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 7 | 6 | 1 | 14 | ||
non coding | 45 | 19 | 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) | ||
5-36195168-A-C | Likely benign (Jan 01, 2024) | |||
5-36195177-T-A | Inborn genetic diseases | Uncertain significance (Mar 02, 2023) | ||
5-36195196-G-A | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Nov 08, 2022) | ||
5-36195203-T-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jan 11, 2024) | ||
5-36195225-A-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Likely benign (Feb 11, 2023) | ||
5-36195237-A-G | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Likely benign (Sep 26, 2023) | ||
5-36195238-T-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jan 30, 2023) | ||
5-36195244-A-G | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jan 24, 2023) | ||
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) | ||
5-36195252-G-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Likely benign (Aug 23, 2022) | ||
5-36195255-A-G | Likely benign (Jul 20, 2018) | |||
5-36195263-A-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jun 20, 2023) | ||
5-36195271-C-T | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jun 14, 2022) | ||
5-36195288-C-A | not specified | Likely benign (Apr 21, 2017) | ||
5-36195346-A-C | Likely benign (May 13, 2021) | |||
5-36195346-A-G | Benign (Jun 29, 2018) | |||
5-36197529-G-C | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Likely benign (Feb 26, 2023) | ||
5-36197535-G-A | Progressive encephalopathy with leukodystrophy due to DECR deficiency • Inborn genetic diseases | Uncertain significance (Jul 21, 2022) | ||
5-36197555-A-G | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Likely benign (Mar 30, 2021) | ||
5-36197556-C-T | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Apr 09, 2023) | ||
5-36197563-G-A | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Jun 03, 2023) | ||
5-36197579-T-C | Likely benign (Mar 01, 2024) | |||
5-36197582-A-G | not specified | Likely benign (Jul 11, 2017) | ||
5-36197598-C-T | Progressive encephalopathy with leukodystrophy due to DECR deficiency | Uncertain significance (Mar 24, 2021) |
GnomAD
Source:
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:
- 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
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