NMRK2

Summary

NMRK2 (nicotinamide riboside kinase 2, HGNC:17871) is a protein-coding gene on chromosome 19p13.3, encoding Nicotinamide riboside kinase 2 (Q9NPI5). Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN).

Enables ribosylnicotinamide kinase activity and ribosylnicotinate kinase activity. Predicted to be involved in NAD metabolic process. Predicted to act upstream of or within negative regulation of myoblast differentiation. Located in nucleoplasm and plasma membrane.

Source: NCBI Gene 27231 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_170678

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17871
Approved symbol	NMRK2
Name	nicotinamide riboside kinase 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MIBP, NRK2
Ensembl gene	ENSG00000077009
Ensembl biotype	protein_coding
OMIM	608705
Entrez	27231

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 21 protein_coding, 1 nonsense_mediated_decay

ENST00000168977, ENST00000593949, ENST00000597889, ENST00000599576, ENST00000616156, ENST00000861808, ENST00000861809, ENST00000861810, ENST00000861811, ENST00000861812, ENST00000861813, ENST00000913543, ENST00000913544, ENST00000913545, ENST00000913546, ENST00000913547, ENST00000913548, ENST00000913549, ENST00000968742, ENST00000968743, ENST00000968744, ENST00000968745

RefSeq mRNA: 5 — MANE Select: NM_170678 NM_001289117, NM_001375467, NM_001375468, NM_001375469, NM_170678

CCDS: CCDS12115, CCDS74259

Canonical transcript exons

ENST00000168977 — 8 exons

Exon	Start	End
ENSE00000664670	3937240	3937288
ENSE00001052267	3933458	3933697
ENSE00001269125	3938603	3938759
ENSE00003123626	3942083	3942416
ENSE00003575836	3936575	3936665
ENSE00003621681	3939900	3939971
ENSE00003642877	3941071	3941177
ENSE00003934546	3933069	3933178

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 99.80.

FANTOM5 (CAGE): breadth broad, TPM avg 11.8685 / max 1977.2637, expressed in 360 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173248	9.7051	332
173247	1.7284	200
173245	0.2229	88
173246	0.1208	72
208652	0.0914	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.80	gold quality
right atrium auricular region	UBERON:0006631	99.73	gold quality
cardiac atrium	UBERON:0002081	99.62	gold quality
heart left ventricle	UBERON:0002084	99.10	gold quality
cardiac ventricle	UBERON:0002082	99.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.40	gold quality
myocardium	UBERON:0002349	98.20	gold quality
gastrocnemius	UBERON:0001388	97.13	gold quality
triceps brachii	UBERON:0001509	96.92	gold quality
left ventricle myocardium	UBERON:0006566	96.70	gold quality
heart right ventricle	UBERON:0002080	96.07	gold quality
gluteal muscle	UBERON:0002000	96.02	gold quality
vastus lateralis	UBERON:0001379	95.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.55	gold quality
heart	UBERON:0000948	95.46	gold quality
quadriceps femoris	UBERON:0001377	95.24	gold quality
muscle of leg	UBERON:0001383	94.97	gold quality
muscle organ	UBERON:0001630	94.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.81	gold quality
biceps brachii	UBERON:0001507	94.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.94	gold quality
skeletal muscle tissue	UBERON:0001134	93.59	gold quality
diaphragm	UBERON:0001103	93.24	gold quality
body of tongue	UBERON:0011876	91.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.54	gold quality
tibialis anterior	UBERON:0001385	90.35	gold quality
muscle tissue	UBERON:0002385	90.13	gold quality
deltoid	UBERON:0001476	88.15	silver quality
vena cava	UBERON:0004087	87.70	gold quality
tongue	UBERON:0001723	82.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	12.21
E-ANND-3	yes	7.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting NMRK2, 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-4283	100.00	66.42	2097
HSA-MIR-381-5P	91.91	65.03	65
HSA-MIR-3186-5P	87.11	67.29	51

Literature-anchored findings (GeneRIF, showing 2)

• Up-regulation of NMRK2 mediated by TFE3 fusions is the key for energy metabolism adaption of Xp11.2 translocation renal cell carcinoma. (PMID:35447281)
• LncRNA like NMRK2 mRNA functions as a key molecular scaffold to enhance mitochondrial respiration of NONO-TFE3 rearranged renal cell carcinoma in an NAD[+] kinase-independent manner. (PMID:37770905)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mibp2	ENSDARG00000101844
mus_musculus	Nmrk2	ENSMUSG00000004939
rattus_norvegicus	Nmrk2	ENSRNOG00000042897
drosophila_melanogaster	CG12016	FBGN0035436

Paralogs (3): NMRK1 (ENSG00000106733), MBIP (ENSG00000151332), MOCS2 (ENSG00000164172)

Protein

Protein identifiers

Nicotinamide riboside kinase 2 — Q9NPI5 (reviewed: Q9NPI5)

Alternative names: Integrin beta-1-binding protein 3, Muscle integrin-binding protein, Nicotinic acid riboside kinase 2, Ribosylnicotinamide kinase 2, Ribosylnicotinic acid kinase 2

All UniProt accessions (3): Q9NPI5, M0QX67, M0R0T8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. Involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. May play a role in the regulation of terminal myogenesis.

Subunit / interactions. Monomer. Interacts with ITGB1 alone or when associated with alpha-7, but not with alpha-5.

Tissue specificity. Predominantly expressed in skeletal muscle and, at a much lower level, in the heart (at protein level). No expression in brain, kidney, liver, lung, pancreas nor placenta.

Induction. Down-regulated during myoblast differentiation.

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis.

Similarity. Belongs to the uridine kinase family. NRK subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPI5-1	1	yes
Q9NPI5-3	2

RefSeq proteins (5): NP_001276046, NP_001362396, NP_001362397, NP_001362398, NP_733778* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF13238

Enzyme classification (BRENDA):

• EC 2.7.1.173 — nicotinate riboside kinase (BRENDA: 3 organisms, 22 substrates, 0 inhibitors, 14 Km, 14 kcat entries)
• EC 2.7.1.22 — ribosylnicotinamide kinase (BRENDA: 8 organisms, 14 substrates, 1 inhibitors, 9 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BETA-D-RIBOSYLNICOTINATE	0.051–30	6
1-(BETA-D-RIBOFURANOSYL)-NICOTINAMIDE	0.068–30	4
BETA-D-RIBOSYLNICOTINAMIDE	0.051–0.063	2
CYTIDINE	15–30	2
TIAZOFURIN	0.11–0.27	2
URIDINE	1.3–17	2
ATP	1.2	1
N-RIBOSYLNICOTINAMIDE	0.08	1
NICOTINAMIDE MONONUCLEOTIDE	0.14	1
NICOTINAMIDE RIBOSIDE	1.1	1
PHOSPHATE	0.28	1

Catalyzed reactions (Rhea), 2 shown:

• beta-nicotinamide D-riboside + ATP = beta-nicotinamide D-ribonucleotide + ADP + H(+) (RHEA:14017)
• beta-D-ribosylnicotinate + ATP = nicotinate beta-D-ribonucleotide + ADP + H(+) (RHEA:25568)

UniProt features (17 total): binding site 10, mutagenesis site 2, chain 1, region of interest 1, splice variant 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPI5-F1	88.56	0.76

Functional residue map

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

Catalytic / active sites (1): 35 (proton acceptor)

Ligand- & substrate-binding residues (10): 134–136; 136–137; 174–176; 9–17; 16; 35–38; 35; 54–55; 130; 131

Mutagenesis-validated functional residues (2):

Position	Phenotype
35	loss of activity.
100	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism

MSigDB gene sets: 84 (showing top): SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GNF2_MYL3, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_MYOBLAST_DIFFERENTIATION, THUM_MIR21_TARGETS_HEART_DISEASE_UP, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (8): NADP+ biosynthetic process (GO:0006741), NAD+ biosynthetic process via the salvage pathway (GO:0034355), negative regulation of myoblast differentiation (GO:0045662), nicotinamide riboside metabolic process (GO:0046495), nicotinate metabolic process (GO:1901847), NAD+ biosynthetic process (GO:0009435), pyridine nucleotide biosynthetic process (GO:0019363), NAD+ metabolic process (GO:0019674)

GO Molecular Function (9): ATP binding (GO:0005524), metal ion binding (GO:0046872), ribosylnicotinamide kinase activity (GO:0050262), nicotinate riboside kinase activity (GO:0061769), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), obsolete nicotinate riboside kinase activity (GO:0034317)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
purine nucleotide biosynthetic process	2
nicotinamide nucleotide biosynthetic process	2
kinase activity	2
phosphotransferase activity, alcohol group as acceptor	2
NADP+ metabolic process	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
myoblast differentiation	1
negative regulation of cell differentiation	1
regulation of myoblast differentiation	1
pyridine nucleoside metabolic process	1
alkaloid metabolic process	1
monocarboxylic acid metabolic process	1
pyridine-containing compound metabolic process	1
NAD+ metabolic process	1
nucleotide biosynthetic process	1
pyridine-containing compound biosynthetic process	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NMRK2	ITGA7	Q13683	760
NMRK2	ITGB1	P05556	655
NMRK2	NAPRT	Q6XQN6	646
NMRK2	A0A2R8YFG2	A0A2R8YFG2	624
NMRK2	PXN	P49023	619
NMRK2	NADSYN1	Q6IA69	616
NMRK2	NMNAT1	Q9HAN9	572
NMRK2	QPRT	Q15274	534
NMRK2	NAMPT	P43490	465
NMRK2	FN1	P02751	442
NMRK2	NMNAT2	Q9BZQ4	439
NMRK2	GPR160	Q9UJ42	423
NMRK2	NF1	P21359	382
NMRK2	ITGB1BP2	Q9UKP3	377
NMRK2	CREB1	P16220	374

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LRP12	NMRK2	psi-mi:“MI:0915”(physical association)	0.510
IGF2	NMRK2	psi-mi:“MI:0915”(physical association)	0.370
NMRK2	SAT1	psi-mi:“MI:0915”(physical association)	0.000
CDKN1A	NMRK2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): NMRK2 (Affinity Capture-Western), NMRK2 (Two-hybrid), ST7 (Affinity Capture-Western), NMRK2 (Affinity Capture-MS), NMRK2 (Two-hybrid), NMRK2 (Two-hybrid), APP (Reconstituted Complex)

ESM2 similar proteins: A4II32, A7MCT6, D3ZRW8, G5E872, O35465, O54783, O55229, P50747, P61797, Q14164, Q14318, Q14CH1, Q1JP61, Q3B7U9, Q496Y0, Q497B8, Q52WX2, Q5I0I5, Q7TQC5, Q7YRZ1, Q7YRZ2, Q7Z2E3, Q7Z695, Q80WC9, Q8BNV1, Q8BYN3, Q8CGA0, Q8HXH0, Q8IYL2, Q8IZ69, Q8K4H4, Q8N371, Q8NF37, Q8NI29, Q8QZX0, Q920N2, Q96EN8, Q9BGQ0, Q9CXT6, Q9D2Q2

Diamond homologs: C0ZAS6, Q6AY91, Q91W63, Q9D7C9, Q9NPI5, Q9NWW6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1277 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3936573:A:AG	acceptor_gain	1.0000
19:3936574:G:GG	acceptor_gain	1.0000
19:3936574:GC:G	acceptor_gain	1.0000
19:3936574:GCAT:G	acceptor_gain	1.0000
19:3936651:G:GT	donor_gain	1.0000
19:3938734:G:GT	donor_gain	1.0000
19:3938735:A:T	donor_gain	1.0000
19:3938754:C:G	donor_gain	1.0000
19:3938760:G:GG	donor_gain	1.0000
19:3941068:CA:C	acceptor_loss	1.0000
19:3941069:A:AC	acceptor_loss	1.0000
19:3941069:A:AG	acceptor_gain	1.0000
19:3941070:G:A	acceptor_loss	1.0000
19:3941070:G:GT	acceptor_gain	1.0000
19:3941070:GT:G	acceptor_gain	1.0000
19:3941070:GTA:G	acceptor_gain	1.0000
19:3941070:GTAC:G	acceptor_gain	1.0000
19:3941070:GTACC:G	acceptor_gain	1.0000
19:3941173:AGTGG:A	donor_loss	1.0000
19:3941174:G:GG	donor_gain	1.0000
19:3941176:GG:G	donor_gain	1.0000
19:3941177:GG:G	donor_gain	1.0000
19:3941178:G:GC	donor_loss	1.0000
19:3941178:G:GG	donor_gain	1.0000
19:3941179:T:A	donor_loss	1.0000
19:3942079:TCAG:T	acceptor_loss	1.0000
19:3942080:CAGT:C	acceptor_loss	1.0000
19:3942081:A:AG	acceptor_gain	1.0000
19:3942082:G:GA	acceptor_gain	1.0000
19:3942082:GT:G	acceptor_gain	1.0000

AlphaMissense

1509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3936595:C:T	T16I	0.997
19:3936657:T:C	F37L	0.997
19:3936659:C:A	F37L	0.997
19:3936659:C:G	F37L	0.997
19:3938740:T:C	F102L	0.997
19:3938742:C:A	F102L	0.997
19:3938742:C:G	F102L	0.997
19:3939965:G:C	R130T	0.997
19:3939966:G:C	R130S	0.997
19:3939966:G:T	R130S	0.997
19:3939968:G:C	R131T	0.997
19:3936652:A:C	D35A	0.996
19:3936652:A:T	D35V	0.996
19:3936653:T:A	D35E	0.996
19:3936653:T:G	D35E	0.996
19:3938737:G:C	G101R	0.996
19:3941108:T:C	F145L	0.996
19:3941110:C:A	F145L	0.996
19:3941110:C:G	F145L	0.996
19:3936580:C:T	T11I	0.995
19:3936650:G:C	Q34H	0.995
19:3936650:G:T	Q34H	0.995
19:3936651:G:C	D35H	0.995
19:3939969:A:C	R131S	0.995
19:3939969:A:T	R131S	0.995
19:3941123:T:A	W150R	0.995
19:3941123:T:C	W150R	0.995
19:3936591:A:C	K15Q	0.994
19:3936660:T:C	F38L	0.994
19:3936662:C:A	F38L	0.994

dbSNP variants (sampled 300 via entrez): RS1000064884 (19:3932402 C>A,T), RS1000587207 (19:3935244 C>G,T), RS1000882643 (19:3931721 G>A,T), RS1000912792 (19:3937203 G>A,C), RS1001092269 (19:3936312 G>A), RS1001476842 (19:3937284 G>A), RS1001533393 (19:3936919 A>G), RS1001545089 (19:3935980 G>A), RS1001583582 (19:3934955 G>A,C), RS1001729306 (19:3934500 T>C), RS1001743722 (19:3941233 C>A), RS1001866934 (19:3935951 C>T), RS1002087654 (19:3935808 C>G,T), RS1002174779 (19:3941532 C>T), RS1002289565 (19:3942766 A>ATGG)

Disease associations

OMIM: gene MIM:608705 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001814_2	Age-related macular degeneration	6.000000e-06
GCST001814_7	Age-related macular degeneration	7.000000e-06
GCST009856_48	Leukocyte telomere length	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Doxorubicin	decreases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
Pioglitazone	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Folic Acid	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases methylation	1
beta-Naphthoflavone	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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