NMNAT2 nicotinamide nucleotide adenylyltransferase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NMNAT2provided by HGNC
Official Full Name: nicotinamide nucleotide adenylyltransferase 2provided by HGNC
Primary source: HGNC:HGNC:16789
See related: Ensembl:ENSG00000157064 MIM:608701; AllianceGenome:HGNC:16789
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PNAT2; C1orf15
Summary: This gene product belongs to the nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme family, members of which catalyze an essential step in NAD (NADP) biosynthetic pathway. Unlike the other human family member, which is localized to the nucleus, and is ubiquitously expressed; this enzyme is cytoplasmic, and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 32.6), heart (RPKM 7.5) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q25.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (183248237..183418380, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (182607574..182777689, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (183217372..183387515, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy.
Title: Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy.
we present the first human variants in NMNAT2 identified in two fetuses with severe skeletal muscle hypoplasia and fetal akinesia. Functional studies in vitro showed that the mutations impair both NMNAT2 NAD(+) synthase and chaperone functions. This work identifies the critical role of NMNAT2 in human development.
Title: Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.
We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia
Title: Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia.
PAM polyubiquitinates NMNAT2 and regulates NMNAT2 protein stability and degradation by the proteasome
Title: PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and degrades NMNAT2.
Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with Kawasaki disease (KD) susceptibility, including the previously reported BLK locus. The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5).
Title: A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease.
analyses found that rs10494561, located in the intron region within NMNAT2, was associated with the severity of the prodromal symptoms of psychosis implicitly, mediated through the volume of the left hemisphere of the superior frontal region
Title: Genome-wide mediation analysis of psychiatric and cognitive traits through imaging phenotypes.
Data indicate a chaperone function of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2), independent from its enzymatic activity, and NMNAT2 complexes with heat shock protein 90 (HSP90) to refold aggregated protein substrates.
Title: NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies.
We confirmed association at NMNAT2 and identified independent SMG7 association with systemic lupus erythematosus in European American and Amerindian/Hispanic ancestries.
Title: Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production.
NMNAT2 might participate in tumorigenesis of CRC.
Title: Nicotinamide Mononucleotide Adenylyl Transferase 2: A Promising Diagnostic and Therapeutic Target for Colorectal Cancer.
Knockdown of NMNAT-2 significantly reduces cellular NAD(+) levels and protects cells from p53-dependent cell death upon DNA damage, suggesting an important functional role of NMNAT-2 in p53-mediated signaling.
Title: The NAD+ synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT-2) is a p53 downstream target.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:374339 (e-PCR)
- UniSTS:156956

SHGC-76014 (e-PCR)
- UniSTS:32372

SHGC-145660 (e-PCR)
- UniSTS:174712

D6S1383E (e-PCR)
- UniSTS:153754

MARC_7499-7500:992008415:1 (e-PCR)
- UniSTS:231332

NIB342 (e-PCR)
- UniSTS:27354

SHGC-75976 (e-PCR)
- UniSTS:77822

D18S1370 (e-PCR)
- UniSTS:55295

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables nicotinamide-nucleotide adenylyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nicotinate-nucleotide adenylyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nicotinate-nucleotide adenylyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein ADP-ribosyltransferase-substrate adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in NAD biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in NAD biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in axon development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of cytoplasmic translation	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleotide biosynthetic process	IC Inferred by Curator more info	PubMed

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in trans-Golgi network	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2

Names: NMN adenylyltransferase 2; NMN/NaMN adenylyltransferase 2; NaMN adenylyltransferase 2; nicotinamide mononucleotide adenylyltransferase 2; nicotinate-nucleotide adenylyltransferase 2; pyridine nucleotide adenylyltransferase 2

NP_055854.1

EC 2.7.7.1

EC 2.7.7.18

NP_733820.1

EC 2.7.7.1

EC 2.7.7.18

XP_054191247.1

EC 2.7.7.1

EC 2.7.7.18

XP_054191248.1

EC 2.7.7.1

EC 2.7.7.18

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_015039.4 → NP_055854.1 nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 isoform 1

See identical proteins and their annotated locations for NP_055854.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AF288395, AL354953, BI493003

Consensus CDS

CCDS1353.1

UniProtKB/Swiss-Prot

O75067, Q5T1Q3, Q8WU99, Q96QW1, Q9BZQ4

UniProtKB/TrEMBL

A8K5S5

Related

ENSP00000287713.6, ENST00000287713.7

Conserved Domains (1) summary

cd09286
Location:9 → 302

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic
NM_170706.4 → NP_733820.1 nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 isoform 2

See identical proteins and their annotated locations for NP_733820.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AL354953, BC020998, BI493003

Consensus CDS

CCDS1354.1

UniProtKB/TrEMBL

A8K5S5

Related

ENSP00000294868.4, ENST00000294868.8

Conserved Domains (1) summary

cd09286
Location:24 → 297

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

183248237..183418380 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

182607574..182777689 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054335272.1 → XP_054191247.1 nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 isoform X1
XM_054335273.1 → XP_054191248.1 nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 isoform X1