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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NMRK1
nicotinamide riboside kinase 1
Chromosome 9 · 9q21.13
NCBI Gene: 54981Ensembl: ENSG00000106733.21HGNC: HGNC:26057UniProt: B3KUG3
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingribosylnicotinamide kinase activitynicotinate riboside kinase activitycytoplasmAbnormality of the skeletal systempyogenic granulomaskin diseaseplacental retention
✦AI Summary

NMRK1 (nicotinamide riboside kinase 1) catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN), respectively, serving as a key enzyme in the NAD+ salvage pathway 1. The enzyme plays a critical role in maintaining hepatic NAD+ levels; NRK1 overexpression in mouse liver elevates NAD+ content, reduces hepatic steatosis, and improves glucose tolerance and insulin sensitivity in both diet-induced and age-induced metabolic dysfunction models 1. NMRK1 expression is downregulated in response to high-fat diet and aging 1. Beyond hepatic metabolism, NMRK1 is a BMAL1-regulated circadian gene in mouse liver, exhibiting rhythmic expression patterns that are lost in BMAL1-knockout models, linking circadian clock function to NAD+ biosynthesis 2. NMRK1 is identified as a shared gene between sarcopenia and type 2 diabetes mellitus pathophysiology 3. Clinically, NMRK1-dependent NAD+ synthesis represents a compensatory pathway in cancer cells resistant to NAMPT inhibitors, with NMRK1 silencing failing to restore sensitivity to such inhibitors in triple-negative breast cancer models 4. These findings establish NMRK1 as a therapeutically relevant target for metabolic diseases and highlight its role in NAD+-dependent cellular adaptation.

Sources cited
1
NRK1 catalyzes NR conversion to NMN and is critical for maintaining hepatic NAD+ levels; overexpression reduces steatosis and improves insulin sensitivity in diet- and age-induced models
PMID: 29678570
2
NMRK1 is a BMAL1-regulated circadian gene in mouse liver with rhythmic expression patterns
PMID: 38183795
3
NMRK1 is identified as a shared differentially expressed gene between sarcopenia and type 2 diabetes mellitus
PMID: 35271662
4
NMRK1 silencing does not increase FK866 sensitivity in FK866-resistant triple-negative breast cancer cells, indicating NMRK1 is not a compensatory mechanism for NAD+ production in this context
PMID: 37148658
5
NMRK1-dependent NAD+ synthesis represents a resistance mechanism to NAMPT inhibitors in tumors dependent on the NAD+ salvage pathway
PMID: 31019297
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.39Weak
pyogenic granulomaOpen Targets
0.23Weak
skin diseaseOpen Targets
0.22Weak
placental retentionOpen Targets
0.22Weak
pregnancy disorderOpen Targets
0.21Weak
nephrotic syndromeOpen Targets
0.20Weak
adolescent idiopathic scoliosisOpen Targets
0.20Weak
gliomaOpen Targets
0.10Suggestive
chronic kidney diseaseOpen Targets
0.08Suggestive
allergic rhinitisOpen Targets
0.07Suggestive
retinopathyOpen Targets
0.07Suggestive
myositisOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
renal fibrosisOpen Targets
0.05Suggestive
osteosarcomaOpen Targets
0.05Suggestive
retinoschisisOpen Targets
0.04Suggestive
acute myeloid leukemiaOpen Targets
0.04Suggestive
SepsisOpen Targets
0.04Suggestive
myeloid leukemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PNPProtein interaction97%NMNAT2Protein interaction97%ENPP1Protein interaction91%NUDT12Protein interaction91%ENPP3Protein interaction90%NMRK2Protein interaction86%
Tissue Expression6 tissues
Liver
100%
Ovary
60%
Lung
59%
Bone Marrow
45%
Brain
29%
Heart
29%
Gene Interaction Network
Click a node to explore
NMRK1PNPNMNAT2ENPP1NUDT12ENPP3NMRK2
PROTEIN STRUCTURE
Preparing viewer…
PDB2QT1 · 1.32 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.67 [0.39–1.20]
RankingsWhere NMRK1 stands among ~20K protein-coding genes
  • #15,637of 20,598
    Most Researched15
  • #12,660of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedNMRK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus.
PMID: 35271662
PLoS One · 2022
1.00
2
Overexpression of NRK1 ameliorates diet- and age-induced hepatic steatosis and insulin resistance.
PMID: 29678570
Biochem Biophys Res Commun · 2018
0.90
3
Identification of BMAL1-Regulated circadian genes in mouse liver and their potential association with hepatocellular carcinoma: Gys2 and Upp2 as promising candidates.
PMID: 38183795
Biochem Biophys Res Commun · 2024
0.80
4
Chemoenzymatic Preparation of 4'-Thioribose NAD
PMID: 30951610
Curr Protoc Nucleic Acid Chem · 2019
0.70
5
Mitochondrial rewiring drives metabolic adaptation to NAD(H) shortage in triple negative breast cancer cells.
PMID: 37148658
Neoplasia · 2023
0.60