NADK2

Summary

NADK2 (NAD kinase 2, mitochondrial, HGNC:26404) is a protein-coding gene on chromosome 5p13.2, encoding NAD kinase 2, mitochondrial (Q4G0N4). Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+).

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.

Source: NCBI Gene 133686 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive encephalopathy with leukodystrophy due to DECR deficiency (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 241 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 63
• MANE Select transcript: NM_001085411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26404
Approved symbol	NADK2
Name	NAD kinase 2, mitochondrial
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30596, MNADK
Ensembl gene	ENSG00000152620
Ensembl biotype	protein_coding
OMIM	615787
Entrez	133686

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000282512, ENST00000381937, ENST00000397338, ENST00000404560, ENST00000502355, ENST00000506945, ENST00000509225, ENST00000511088, ENST00000511613, ENST00000514504, ENST00000617628, ENST00000948923, ENST00000948924

RefSeq mRNA: 4 — MANE Select: NM_001085411 NM_001085411, NM_001287340, NM_001287341, NM_153013

CCDS: CCDS3917, CCDS47197, CCDS75235

Canonical transcript exons

ENST00000381937 — 12 exons

Exon	Start	End
ENSE00001082241	36219596	36219679
ENSE00001082244	36217748	36217884
ENSE00002068299	36192589	36195282
ENSE00003472169	36200227	36200280
ENSE00003492221	36211844	36211922
ENSE00003492476	36197541	36197664
ENSE00003500193	36225542	36225623
ENSE00003517146	36207170	36207265
ENSE00003563811	36227477	36227565
ENSE00003620101	36201106	36201161
ENSE00003672078	36226475	36226563
ENSE00003847187	36241499	36241925

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7384 / max 185.3021, expressed in 1748 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61316	5.4616	1593
61313	3.5311	1260
61315	0.9664	496
61317	0.5795	317
61314	0.1437	59
61318	0.0369	7
61310	0.0193	5

Top tissues by expression

258 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	97.96	gold quality
right lobe of liver	UBERON:0001114	97.92	gold quality
epithelial cell of pancreas	CL:0000083	97.45	gold quality
ventricular zone	UBERON:0003053	96.46	gold quality
endothelial cell	CL:0000115	96.39	gold quality
medulla oblongata	UBERON:0001896	95.90	gold quality
renal medulla	UBERON:0000362	95.61	gold quality
kidney epithelium	UBERON:0004819	95.43	gold quality
adrenal tissue	UBERON:0018303	95.25	gold quality
oviduct epithelium	UBERON:0004804	95.16	gold quality
superior vestibular nucleus	UBERON:0007227	94.91	gold quality
ventral tegmental area	UBERON:0002691	94.90	gold quality
medial globus pallidus	UBERON:0002477	94.89	gold quality
corpus callosum	UBERON:0002336	94.88	gold quality
globus pallidus	UBERON:0001875	94.74	gold quality
saphenous vein	UBERON:0007318	94.54	gold quality
parotid gland	UBERON:0001831	94.53	gold quality
layer of synovial tissue	UBERON:0007616	94.36	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.98	gold quality
cardia of stomach	UBERON:0001162	93.73	gold quality
lateral globus pallidus	UBERON:0002476	93.65	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.56	gold quality
subthalamic nucleus	UBERON:0001906	93.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.48	gold quality
synovial joint	UBERON:0002217	93.44	gold quality
sperm	CL:0000019	93.38	gold quality
penis	UBERON:0000989	93.28	gold quality
pancreatic ductal cell	CL:0002079	93.09	gold quality
substantia nigra pars compacta	UBERON:0001965	93.01	gold quality
body of pancreas	UBERON:0001150	92.77	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting NADK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 9)

• exhibits NAD kinase activity, utilizing ATP or inorganic polyphosphate, and is localized in mitochondria of HEK293A cells (PMID:23212377)
• MNADK is localized to mitochondria in Hep G2 cells, and a recombinant MNADK showed NAD kinase activity. MNADK is abundant in mitochondrion-rich tissues, such as liver. MNADK expression was suppressed in human liver tumors. Identification of MNADK immediately suggests a model in which NADK and MNADK are responsible for de novo synthesis of NADP(+) in cytosol and mitochondria, respectively. (PMID:23616928)
• An autosomal recessive defect in NADK2 causes mitochondrial NADPH deficiency with secondary deficiencies in several mitochondrial processes including polyunsaturated fatty acid oxidation and lysine degradation. (PMID:24847004)
• The use of whole exome sequencing has allowed us to identify a new homozygous mutation in NADK2, leading to a premature stop codon and absence of protein. To our knowledge this is the second reported individual with mutations in NADK2. (PMID:27940755)
• Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes. (PMID:29388319)
• Mitochondrial NADP(H) generation is essential for proline biosynthesis. (PMID:33888598)
• Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation. (PMID:35868311)
• Deleting MNADK (NADK2) in mice reduced fat oxidation upon energy demand triggered by endurance exercise or fasting. NADK2 is a major metabolic regulator upon increased energy demand. (PMID:35944895)
• The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand. (PMID:35944895)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nadk2	ENSDARG00000007181
mus_musculus	Nadk2	ENSMUSG00000022253
rattus_norvegicus	Nadk2	ENSRNOG00000054157
drosophila_melanogaster	Nadk2	FBGN0033373
caenorhabditis_elegans		WBGENE00012463
caenorhabditis_elegans		WBGENE00022307

Protein

Protein identifiers

NAD kinase 2, mitochondrial — Q4G0N4 (reviewed: Q4G0N4)

Alternative names: Mitochondrial NAD kinase, NAD kinase domain-containing protein 1, mitochondrial

All UniProt accessions (5): Q4G0N4, A0A0C4DGV3, B7Z8V7, D6RHI4, H0Y9H7

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Tissue specificity. Widely expressed.

Disease relevance. 2,4-dienoyl-CoA reductase deficiency (DECRD) [MIM:616034] A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by NADH, NADPH and NADP(+).

Similarity. Belongs to the NAD kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q4G0N4-1	1	yes
Q4G0N4-2	2
Q4G0N4-3	3

RefSeq proteins (4): NP_001078880, NP_001274269, NP_001274270, NP_694558 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002504	NADK	Family
IPR012355	NADK2_mit	Family
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017437	ATP-NAD_kinase_PpnK-typ_C	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily

Pfam: PF01513

Enzyme classification (BRENDA):

• EC 2.7.1.23 — NAD+ kinase (BRENDA: 57 organisms, 133 substrates, 131 inhibitors, 140 Km, 41 kcat entries)

Substrate kinetics (BRENDA)

21 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.032–4.5	55
NAD+	0.022–6.5	55
POLYPHOSPHATE	2.2–2.7	4
GTP	0.2–2.86	3
NADH	0.042–2	3
NADP+	0.18–1.01	3
POLY(P)4	0.21–0.33	2
ADP	4.3	1
CTP	0.59	1
FRUCTOSE-1,6-BISPHOSPHATE	0.43	1
ITP	1.54	1
NADPH	0.3	1
POLYPHOSPHATE(20)	5.9	1
POLYPHOSPHATE(25)	17.2	1
POLYPHOSPHATE(45)	14.1	1

Catalyzed reactions (Rhea), 1 shown:

• NAD(+) + ATP = ADP + NADP(+) + H(+) (RHEA:18629)

UniProt features (51 total): strand 19, helix 14, modified residue 8, turn 4, splice variant 2, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7R4M	X-RAY DIFFRACTION	2.29
7R4L	X-RAY DIFFRACTION	2.6
7N29	X-RAY DIFFRACTION	2.8
7R4J	X-RAY DIFFRACTION	2.95
7R4K	X-RAY DIFFRACTION	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0N4-F1	84.13	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 367, 397, 76, 76, 188, 302, 317, 317

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 276 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_NADPPLUS_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, AACTTT_UNKNOWN, CUI_TCF21_TARGETS_2_DN, ACEVEDO_LIVER_CANCER_UP, YAMAZAKI_TCEB3_TARGETS_DN, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_MATRIX

GO Biological Process (2): NADP+ biosynthetic process (GO:0006741), NAD+ metabolic process (GO:0019674)

GO Molecular Function (7): NAD+ kinase activity (GO:0003951), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, alcohol group as acceptor (GO:0016773)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of proteins	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transferase activity, transferring phosphorus-containing groups	2
purine nucleotide biosynthetic process	1
NADP+ metabolic process	1
nicotinamide nucleotide biosynthetic process	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NADK2	NADK	O95544	792
NADK2	CALM1	P02593	542
NADK2	NMNAT1	Q9HAN9	500
NADK2	NADSYN1	Q6IA69	489
NADK2	NNT	Q13423	478
NADK2	A0A2R8YFG2	A0A2R8YFG2	463
NADK2	HMGXB3	Q12766	461
NADK2	NAPRT	Q6XQN6	453
NADK2	LMBRD2	Q68DH5	436
NADK2	RANBP3L	Q86VV4	395
NADK2	MTAP	Q13126	387
NADK2	ACSF2	Q96CM8	386
NADK2	PYCR1	P32322	385
NADK2	TMEM267	Q0VDI3	385
NADK2	QPRT	Q15274	373

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ETFRF1	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
ORF70	PDHX	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MTPN	PLCG1	psi-mi:“MI:0914”(association)	0.350
NADK2	ACTB	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	PIPSL	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (76): NADK2 (Affinity Capture-MS), NADK2 (Affinity Capture-MS), NADK2 (Affinity Capture-MS), NADK2 (Affinity Capture-MS), NADK2 (Proximity Label-MS), NADK2 (Proximity Label-MS), NADK2 (Proximity Label-MS), NADK2 (Proximity Label-MS), NADK2 (Proximity Label-MS), NADK2 (Affinity Capture-MS), NADK2 (Affinity Capture-MS), NADK2 (Proximity Label-MS), NADK2 (Proximity Label-MS), NADK2 (Affinity Capture-MS), NADK2 (Affinity Capture-MS)

ESM2 similar proteins: A2AV36, A7E2V1, C0LT23, F4JKI3, O00763, O08764, O95870, P47823, P51398, P52429, P82922, Q08BI9, Q08CZ6, Q13144, Q1HCL7, Q1JPD2, Q1LWG4, Q1PDI2, Q28DH9, Q28DV7, Q49MI3, Q4G0N4, Q4R8P0, Q4U2V3, Q56YN3, Q58E26, Q5EBA1, Q5JK52, Q5R6S0, Q5ZJT0, Q60E60, Q64350, Q6DDX8, Q6MG55, Q6PBN5, Q7TQI7, Q7XQT2, Q7ZW00, Q7ZYJ3, Q80YD1

Diamond homologs: Q08CZ6, Q1HCL7, Q4G0N4, Q500Y9, Q8C5H8, Q6EQG2, A0L8H9, A0LG64, A0Q7Q7, A1U2D4, A5F368, A5IHZ7, A7I809, A7NAY2, A8GI41, B2SDS9, B3DSX1, B3EI21, B3QLE4, B8GEC2, C3LTA3, Q031V6, Q0BMU7, Q1QXZ6, Q2A4H0, Q2SDI1, Q3A241, Q3IR96, Q46AH3, Q5L911, Q5WSY8, Q5X168, Q5ZRQ7, Q64P72, Q66DA9, Q67NC1, Q6D8Y0, Q6MII5, Q8A0V4, Q8G5G8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

241 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	106
Likely benign	106
Benign	22

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
830231	NM_001085411.3(NADK2):c.956+6T>C	Pathogenic
156239	NM_001085411.3(NADK2):c.1018C>T (p.Arg340Ter)	Likely pathogenic

SpliceAI

1757 predictions. Top by Δscore:

Variant	Effect	Δscore
5:36195281:CC:C	acceptor_gain	1.0000
5:36195282:CC:C	acceptor_gain	1.0000
5:36197535:GCTTA:G	donor_loss	1.0000
5:36197536:CTTA:C	donor_loss	1.0000
5:36197537:TTAC:T	donor_loss	1.0000
5:36197538:TACTT:T	donor_loss	1.0000
5:36197539:A:AC	donor_gain	1.0000
5:36197539:A:T	donor_loss	1.0000
5:36197540:C:CC	donor_gain	1.0000
5:36197540:CT:C	donor_gain	1.0000
5:36197540:CTT:C	donor_gain	1.0000
5:36197540:CTTT:C	donor_gain	1.0000
5:36197540:CTTTG:C	donor_gain	1.0000
5:36197660:TGTTA:T	acceptor_gain	1.0000
5:36197661:GTTA:G	acceptor_gain	1.0000
5:36197662:TTA:T	acceptor_gain	1.0000
5:36197662:TTAC:T	acceptor_loss	1.0000
5:36197663:TA:T	acceptor_gain	1.0000
5:36197663:TACTA:T	acceptor_loss	1.0000
5:36197665:C:CC	acceptor_gain	1.0000
5:36197665:CTAC:C	acceptor_loss	1.0000
5:36197668:C:CT	acceptor_gain	1.0000
5:36200222:CTGA:C	donor_loss	1.0000
5:36200223:TGAC:T	donor_loss	1.0000
5:36200224:GACC:G	donor_loss	1.0000
5:36200225:A:C	donor_loss	1.0000
5:36200277:TTTG:T	acceptor_gain	1.0000
5:36200278:TTG:T	acceptor_gain	1.0000
5:36200278:TTGCT:T	acceptor_loss	1.0000
5:36200279:TG:T	acceptor_gain	1.0000

AlphaMissense

2840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:36195199:G:T	A425D	1.000
5:36195217:A:G	F419S	1.000
5:36195235:C:T	G413E	1.000
5:36195238:T:A	D412V	1.000
5:36195239:C:G	D412H	1.000
5:36195261:A:C	C404W	1.000
5:36195268:G:A	S402F	1.000
5:36195274:A:T	V400D	1.000
5:36197573:G:C	F386L	1.000
5:36197573:G:T	F386L	1.000
5:36197575:A:G	F386L	1.000
5:36201161:C:A	W319C	1.000
5:36201161:C:G	W319C	1.000
5:36207171:A:G	W319R	1.000
5:36207171:A:T	W319R	1.000
5:36207182:C:T	G315E	1.000
5:36207188:C:A	G313V	1.000
5:36207188:C:T	G313E	1.000
5:36207189:C:G	G313R	1.000
5:36207189:C:T	G313R	1.000
5:36207206:C:T	G307E	1.000
5:36207207:C:A	G307W	1.000
5:36207211:A:C	S305R	1.000
5:36207211:A:T	S305R	1.000
5:36207213:T:G	S305R	1.000
5:36207214:C:A	K304N	1.000
5:36207214:C:G	K304N	1.000
5:36211862:C:T	G281E	1.000
5:36211863:C:A	G281W	1.000
5:36211867:G:C	F279L	1.000

dbSNP variants (sampled 300 via entrez): RS1000052327 (5:36201087 T>C), RS1000087711 (5:36213643 T>C), RS1000097524 (5:36240943 C>A), RS1000113633 (5:36213055 A>C), RS1000132333 (5:36234184 C>T), RS1000152632 (5:36194664 A>G), RS1000239140 (5:36206345 G>A), RS1000347545 (5:36221369 C>T), RS1000357724 (5:36199167 G>A), RS1000514663 (5:36206340 G>A), RS1000554203 (5:36240668 C>A,T), RS1000559585 (5:36239351 T>C), RS1000593308 (5:36192172 A>G), RS1000596879 (5:36205972 A>G), RS1000617477 (5:36232390 C>T)

Disease associations

OMIM: gene MIM:615787 | disease phenotypes: MIM:616034, MIM:615987

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive encephalopathy with leukodystrophy due to DECR deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive encephalopathy with leukodystrophy due to DECR deficiency	Moderate	AR

Mondo (2): progressive encephalopathy with leukodystrophy due to DECR deficiency (MONDO:0014464), Bardet-Biedl syndrome 10 (MONDO:0014438)

Orphanet (2): Progressive encephalopathy with leukodystrophy due to DECR deficiency (Orphanet:431361), Bardet-Biedl syndrome (Orphanet:110)

HPO phenotypes

63 total (30 of 63 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000496	Abnormality of eye movement
HP:0000540	Hypermetropia
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001298	Encephalopathy
HP:0001319	Neonatal hypotonia
HP:0001332	Dystonia
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001733	Pancreatitis
HP:0001942	Metabolic acidosis
HP:0001947	Renal tubular acidosis
HP:0001992	Organic aciduria
HP:0002033	Poor suck
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002151	Increased circulating lactate concentration

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_17	Night sleep phenotypes	4.000000e-06
GCST003542_3	Night sleep phenotypes	1.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C565624	2,4-Dienoyl-CoA Reductase Deficiency (supp.)
C565919	Bardet-Biedl Syndrome 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects cotreatment	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
uranyl acetate	increases expression	1
bisphenol A	decreases methylation	1
mono-(2-ethylhexyl)phthalate	increases abundance, decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	decreases expression	1
bisphenol S	increases expression	1
Bortezomib	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7VH	Ubigene A-549 NADK2 KO	Cancer cell line	Male
CVCL_E2D2	HAP1 NADK2 (-) 2	Cancer cell line	Male
CVCL_E2D3	HAP1 NADK2 (-) 3	Cancer cell line	Male
CVCL_XQ85	HAP1 NADK2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.