This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009] See more...

Aliases for NPFFR2 Gene

Aliases for NPFFR2 Gene

  • Neuropeptide FF Receptor 2 2 3 4 5
  • NPFF2 2 3 4
  • NPGPR 2 3 4
  • Neuropeptide G-Protein Coupled Receptor 3 4
  • G-Protein Coupled Receptor HLWAR77 3 4
  • G-Protein Coupled Receptor 74 3 4
  • Neuropeptide FF 2 2 3
  • GPR74 3 4
  • G Protein-Coupled Receptor 74 2
  • HLWAR77 3
  • NPFFR2 5

External Ids for NPFFR2 Gene

Previous HGNC Symbols for NPFFR2 Gene

  • GPR74

Previous GeneCards Identifiers for NPFFR2 Gene

  • GC04P073116
  • GC04P072897
  • GC04P068702

Summaries for NPFFR2 Gene

Entrez Gene Summary for NPFFR2 Gene

  • This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

GeneCards Summary for NPFFR2 Gene

NPFFR2 (Neuropeptide FF Receptor 2) is a Protein Coding gene. Diseases associated with NPFFR2 include Nutmeg Liver. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and neuropeptide receptor activity. An important paralog of this gene is NPFFR1.

UniProtKB/Swiss-Prot Summary for NPFFR2 Gene

  • Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Tocris Summary for NPFFR2 Gene

  • Neuropeptide FF/AF (NPFF) receptors are a group of Gi/Go-protein-coupled receptors that are divided into two subtypes; NPFF1 and NPFF2. NPFF receptors have been implicated in hormonal modulation, regulation of food intake, thermoregulation and nociception.

Gene Wiki entry for NPFFR2 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NPFFR2 Gene

Genomics for NPFFR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NPFFR2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J072031 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE CraniofacialAtlas 268 +0.6 597 2 SCRT1 GLIS1 CEBPB GLIS2 POLR2A SCRT2 NPFFR2 piR-37052 ADAMTS3
GH04J072039 Promoter 1.3 EPDnew Ensembl 268.6 +7.6 7596 0.8 NCOR1 NFATC3 NBN NKRF SKIL HLTF SUPT5H SMARCA4 FOXM1 RAD51 NPFFR2 piR-37052 ADAMTS3
GH04J072094 Promoter 0.3 EPDnew 250.2 +62.9 62940 0.1 NPFFR2 piR-40163-075 piR-37052 ADAMTS3
GH04J072113 Enhancer 1.3 FANTOM5 Ensembl ENCODE 7.4 +81.0 80974 1.6 BCLAF1 SP1 JUND ATF2 ZBTB10 BCL11A CEBPB ZNF592 TRIM22 BHLHE40 HMGA1P2 NPFFR2 piR-40163-075 piR-37052 ADAMTS3
GH04J072209 Enhancer 0.7 Ensembl ENCODE 4.7 +177.7 177696 1.8 FOXA1 IKZF1 NR2F1 JUNB FOS IKZF2 CREM DPF2 RUNX3 RELB HSALNG0035100 NPFFR2 HSALNG0035101 ADAMTS3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NPFFR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NPFFR2

Top Transcription factor binding sites by QIAGEN in the NPFFR2 gene promoter:
  • AML1a
  • AREB6
  • Cart-1
  • FOXO3
  • FOXO3a
  • FOXO3b

Genomic Locations for NPFFR2 Gene

Latest Assembly
chr4:72,031,804-72,148,305
(GRCh38/hg38)
Size:
116,502 bases
Orientation:
Plus strand

Previous Assembly
chr4:72,897,717-73,014,022
(GRCh37/hg19 by Entrez Gene)
Size:
116,306 bases
Orientation:
Plus strand

chr4:72,897,521-73,013,784
(GRCh37/hg19 by Ensembl)
Size:
116,264 bases
Orientation:
Plus strand

Genomic View for NPFFR2 Gene

Genes around NPFFR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPFFR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPFFR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPFFR2 Gene

Proteins for NPFFR2 Gene

  • Protein details for NPFFR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5X5-NPFF2_HUMAN
    Recommended name:
    Neuropeptide FF receptor 2
    Protein Accession:
    Q9Y5X5
    Secondary Accessions:
    • Q96RV1
    • Q9NR49

    Protein attributes for NPFFR2 Gene

    Size:
    522 amino acids
    Molecular mass:
    60270 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAK58513.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for NPFFR2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPFFR2 Gene

Post-translational modifications for NPFFR2 Gene

  • Glycosylation at Asn110, Asn122, Asn133, and Asn300
  • Modification sites at PhosphoSitePlus

Other Protein References for NPFFR2 Gene

No data available for DME Specific Peptides for NPFFR2 Gene

Domains & Families for NPFFR2 Gene

Gene Families for NPFFR2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • G-protein coupled receptors
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for NPFFR2 Gene

InterPro:
Blocks:
  • Neuropeptide FF receptor family signature
  • Type 2 neuropeptide FF receptor signature

Suggested Antigen Peptide Sequences for NPFFR2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ75415, highly similar to Homo sapiens G protein-coupled receptor 74 (GPR74), transcript variant 2, mRNA (A0PJM9_HUMAN)
  • Neuropeptide G-protein coupled receptor (NPFF2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y5X5

UniProtKB/Swiss-Prot:

NPFF2_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with NPFFR2: view

Function for NPFFR2 Gene

Molecular function for NPFFR2 Gene

UniProtKB/Swiss-Prot Function:
Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Phenotypes From GWAS Catalog for NPFFR2 Gene

Gene Ontology (GO) - Molecular Function for NPFFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity TAS,IBA 21873635
GO:0005515 protein binding IPI --
GO:0008188 neuropeptide receptor activity IEA --
GO:0031628 opioid receptor binding IEA --
GO:0042277 peptide binding IBA 21873635
genes like me logo Genes that share ontologies with NPFFR2: view
genes like me logo Genes that share phenotypes with NPFFR2: view

Animal Models for NPFFR2 Gene

MGI Knock Outs for NPFFR2:

Animal Models for research

  • Taconic Biosciences Mouse Models for NPFFR2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPFFR2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for NPFFR2 Gene

Localization for NPFFR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPFFR2 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPFFR2 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 4
nucleus 2
extracellular 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Actin filaments (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NPFFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS,IBA 21873635
GO:0015629 actin cytoskeleton IDA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with NPFFR2: view

Pathways & Interactions for NPFFR2 Gene

genes like me logo Genes that share pathways with NPFFR2: view

SIGNOR curated interactions for NPFFR2 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NPFFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007218 neuropeptide signaling pathway IEA --
GO:0009582 detection of abiotic stimulus TAS 10851242
GO:0043408 regulation of MAPK cascade IEA --
genes like me logo Genes that share ontologies with NPFFR2: view

Drugs & Compounds for NPFFR2 Gene

(19) Drugs for NPFFR2 Gene - From: ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pancreatic Polypeptide Investigational Pharma 24
neuropeptide FF Pharma Agonist, Full agonist Endogenous NPFF1 and NPFF2 agonist 0
BIBP3226 Pharma Antagonist 0
Neuropeptide AF (human) Pharma Implicated in pain modulation, opioid function and metabolism 0
Neuropeptide SF (mouse, rat) Pharma NPFF1 and NPFF2 agonist 0

(1) Additional Compounds for NPFFR2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(3) Tocris Compounds for NPFFR2 Gene

Compound Action Cas Number
Neuropeptide AF (human) Implicated in pain modulation, opioid function and metabolism 192387-38-5
Neuropeptide FF Endogenous NPFF1 and NPFF2 agonist 99566-27-5
Neuropeptide SF (mouse, rat) NPFF1 and NPFF2 agonist 230960-31-3

(5) ApexBio Compounds for NPFFR2 Gene

Compound Action Cas Number
BIBP 3226 trifluoroacetate Mixed NPY1-R and NPFF receptor inhibitor 1068148-47-9
Neuropeptide AF (human) 192387-38-5
Neuropeptide SF (mouse, rat) 230960-31-3
RF 9 neuropeptide FF receptors antagonist 876310-60-0
RFRP 3 (human) 311309-27-0
genes like me logo Genes that share compounds with NPFFR2: view

Drug products for research

Transcripts for NPFFR2 Gene

mRNA/cDNA for NPFFR2 Gene

3 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPFFR2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for NPFFR2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c
SP1: - -
SP2: - - -
SP3: -
SP4: - - - -
SP5:

Relevant External Links for NPFFR2 Gene

GeneLoc Exon Structure for
NPFFR2

Expression for NPFFR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NPFFR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NPFFR2 Gene

This gene is overexpressed in Brain - Hypothalamus (x5.5) and Brain - Anterior cingulate cortex (BA24) (x4.4).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NPFFR2

SOURCE GeneReport for Unigene cluster for NPFFR2 Gene:

Hs.99231

mRNA Expression by UniProt/SwissProt for NPFFR2 Gene:

Q9Y5X5-NPFF2_HUMAN
Tissue specificity: Isoform 1 is abundant in placenta. Relatively highly expressed in thymus, testis, and small intestine. Expressed at low levels in several tissues including spleen, prostate, brain, heart, ovary, colon, kidney, lung, liver and pancreas and not expressed in skeletal muscle and leukocytes. Isoform 2 expression is highest in placenta (but at relatively low level compared to isoform 1). Very low level of expression in numerous tissues including adipose tissue and many brain regions. Isoform 3 is expressed in brain and heart and, at lower levels, in kidney, liver, lung and pancreas.

Evidence on tissue expression from TISSUES for NPFFR2 Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with NPFFR2: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NPFFR2 Gene

Orthologs for NPFFR2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NPFFR2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NPFFR2 29 30
  • 99.23 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NPFFR2 29 30
  • 87.99 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NPFFR2 29 30
  • 86.26 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Npffr2 29 16 30
  • 82.25 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Npffr2 29
  • 81.57 (n)
Oppossum
(Monodelphis domestica)
Mammalia NPFFR2 30
  • 72 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NPFFR2 30
  • 56 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NPFFR2 29 30
  • 68.61 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NPFFR2 30
  • 61 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia npffr2 29
  • 65.54 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.19325 29
Zebrafish
(Danio rerio)
Actinopterygii npffr2.1 29
  • 64.95 (n)
NPFFR2.1 30
  • 61 (a)
OneToMany
npffr2.2 30
  • 55 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta SIFR 29 30
  • 48.15 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta GPRNNA7 29
  • 46.44 (n)
Species where no ortholog for NPFFR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for NPFFR2 Gene

ENSEMBL:
Gene Tree for NPFFR2 (if available)
TreeFam:
Gene Tree for NPFFR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NPFFR2: view image
Alliance of Genome Resources:
Additional Orthologs for NPFFR2

Paralogs for NPFFR2 Gene

(13) SIMAP similar genes for NPFFR2 Gene using alignment to 2 proteins:

  • NPFF2_HUMAN
  • A0PJM9_HUMAN
genes like me logo Genes that share paralogs with NPFFR2: view

Variants for NPFFR2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NPFFR2 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs115834666 Benign: not provided 72,032,006(+) C/G
NM_004885.2(NPFFR2):c.105C>G (p.Ser35Arg)
MISSENSE
rs61733659 Benign: not provided 72,146,992(+) T/C
NM_004885.2(NPFFR2):c.749T>C (p.Val250Ala)
MISSENSE
rs77060411 Likely Benign: not provided 72,138,099(+) G/A
NM_004885.2(NPFFR2):c.694G>A (p.Ala232Thr)
MISSENSE
rs77812923 Benign: not provided 72,128,808(+) A/G
NM_004885.2(NPFFR2):c.523A>G (p.Asn175Asp)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NPFFR2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NPFFR2 Gene

Variant ID Type Subtype PubMed ID
dgv9128n54 CNV loss 21841781
esv22388 CNV loss 19812545
esv2289844 CNV deletion 18987734
esv2663080 CNV deletion 23128226
esv3305821 CNV mobile element insertion 20981092
esv3393306 CNV insertion 20981092
esv3569516 CNV loss 25503493
nsv1114546 CNV deletion 24896259
nsv1119008 CNV deletion 24896259
nsv508287 CNV deletion 20534489
nsv518185 CNV loss 19592680
nsv829968 CNV gain 17160897

Variation tolerance for NPFFR2 Gene

Residual Variation Intolerance Score: 84.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.72; 57.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NPFFR2 Gene

Human Gene Mutation Database (HGMD)
NPFFR2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPFFR2
Leiden Open Variation Database (LOVD)
NPFFR2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPFFR2 Gene

Disorders for NPFFR2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NPFFR2 Gene - From: COP

Disorder Aliases PubMed IDs
nutmeg liver
  • chronic passive congestion of liver
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NPFFR2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NPFFR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NPFFR2 Gene

Publications for NPFFR2 Gene

  1. Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor. (PMID: 10851242) Elshourbagy NA … Sarau HM (The Journal of biological chemistry 2000) 2 3 4
  2. Identification and characterization of two G protein-coupled receptors for neuropeptide FF. (PMID: 11024015) Bonini JA … Borowsky B (The Journal of biological chemistry 2000) 3 4 22
  3. Sequence and tissue distribution of a novel G-protein-coupled receptor expressed prominently in human placenta. (PMID: 10079187) Cikos S … Koppel J (Biochemical and biophysical research communications 1999) 2 3 4
  4. A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis. (PMID: 17503329) Dahlman I … Arner P (American journal of human genetics 2007) 3 40
  5. Characterization of the NPGP receptor and identification of a novel short mRNA isoform in human hypothalamus. (PMID: 12609745) Laemmle B … Wieland HA (Regulatory peptides 2003) 3 22

Products for NPFFR2 Gene

Sources for NPFFR2 Gene