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    NPAS3 neuronal PAS domain protein 3 [ Homo sapiens (human) ]

    Gene ID: 64067, updated on 2-Nov-2024

    Summary

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    Official Symbol
    NPAS3provided by HGNC
    Official Full Name
    neuronal PAS domain protein 3provided by HGNC
    Primary source
    HGNC:HGNC:19311
    See related
    Ensembl:ENSG00000151322 MIM:609430; AllianceGenome:HGNC:19311
    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
    MOP6; PASD6; bHLHe12
    Summary
    This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
    Expression
    Biased expression in brain (RPKM 3.9), endometrium (RPKM 1.3) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NPAS3 in Genome Data Viewer
    Location:
    14q13.1
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (32934785..33804173)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (27131685..28001533)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (33408085..34273379)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 11725 Neighboring gene A-kinase anchoring protein 6 Neighboring gene MT-CO1 pseudogene 2 Neighboring gene uncharacterized LOC124903298 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8241 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr14:33281639-33282368 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr14:33282369-33283098 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:33603289-33603866 Neighboring gene NANOG hESC enhancer GRCh37_chr14:33922151-33922707 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:33944722-33945332 Neighboring gene NANOG hESC enhancer GRCh37_chr14:33946898-33947463 Neighboring gene uncharacterized LOC124903299 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:34021175-34021810 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:34033742-34034271 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:34081250-34081760 Neighboring gene uncharacterized LOC124903300 Neighboring gene Sharpr-MPRA regulatory region 868 Neighboring gene small nucleolar RNA, H/ACA box 89 Neighboring gene Sharpr-MPRA regulatory region 9495 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:34366891-34367394 Neighboring gene GATA motif-containing MPRA enhancer 110 Neighboring gene NANOG hESC enhancer GRCh37_chr14:34400622-34401183 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:34407170-34408141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5660 Neighboring gene uncharacterized LOC102724945 Neighboring gene uncharacterized LOC105370446 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:34433111-34433612 Neighboring gene egl-9 family hypoxia inducible factor 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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?
    1. SYMPTOM SEVERITY IN SCHIZOPHRENIA PATIENTS WITH NPAS3, DYSBINDIN-1 AND/OR TRIOBP PROTEIN PATHOLOGY IN THEIR BLOOD SERUM: A PANSS-BASED FOLLOW UP STUDY.
      Title: SYMPTOM SEVERITY IN SCHIZOPHRENIA PATIENTS WITH NPAS3, DYSBINDIN-1 AND/OR TRIOBP PROTEIN PATHOLOGY IN THEIR BLOOD SERUM: A PANSS-BASED FOLLOW UP STUDY.
    2. Npas3 deficiency impairs cortical astrogenesis and induces autistic-like behaviors.
      Title: Npas3 deficiency impairs cortical astrogenesis and induces autistic-like behaviors.
    3. Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.
      Title: Molecular characterisation of rare loss-of-function NPAS3 and NPAS4 variants identified in individuals with neurodevelopmental disorders.
    4. NPAS3 is a true transcription factor capable of regulating expression of target genes through their promoters by directly cooperating with ARNT.
      Title: Molecular analysis of NPAS3 functional domains and variants.
    5. Study provides a clear, unbiased view of the full spectrum of genes regulated by NPAS1 and NPAS3 and shows that these transcription factors are master regulators of neuropsychiatric function. These findings expose the molecular pathophysiology of NPAS1/3 mutations and provide a striking example of the shared, combinatorial nature of molecular pathways that underlie diagnostically distinct neuropsychiatric conditions.
      Title: Neuronal PAS Domain Proteins 1 and 3 Are Master Regulators of Neuropsychiatric Risk Genes.
    6. Here the authors examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets.
      Title: NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.
    7. Authors hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia.
      Title: Cumulative role of rare and common putative functional genetic variants at NPAS3 in schizophrenia susceptibility.
    8. Identification of NPAS3-V304I helps strengthen the hypothesis that NPAS3 is involved in schizophrenia pathogenesis
      Title: A mutation in NPAS3 segregates with mental illness in a small family.
    9. The accelerated non-coding region 2xHAR142 of NPAS3 behaves as a developmental enhancer in the forebrain of transgenic mice.
      Title: A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice.
    10. Results indicate that the high density of HAEs present in the human NPAS3 locus could have modified the spatiotemporal expression pattern of NPAS3 in the developing human brain and, therefore, contributed to human brain evolution.
      Title: The developmental brain gene NPAS3 contains the largest number of accelerated regulatory sequences in the human genome.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.
    EBI GWAS Catalog
    A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.
    EBI GWAS Catalog
    A genome-wide association study in the genetic analysis of idiopathic thrombophilia project suggests sex-specific regulation of mitochondrial DNA levels.
    EBI GWAS Catalog
    A genome-wide association study of inflammatory biomarker changes in response to fenofibrate treatment in the Genetics of Lipid Lowering Drug and Diet Network.
    EBI GWAS Catalog
    Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.
    EBI GWAS Catalog
    Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression.
    EBI GWAS Catalog
    Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10003, FLJ11138, FLJ11605

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in positive regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    neuronal PAS domain-containing protein 3
    Names
    PAS domain-containing protein 6
    basic-helix-loop-helix-PAS protein MOP6
    class E basic helix-loop-helix protein 12
    member of PAS protein 6
    neuronal PAS3

    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.

    Genomic

    1. NG_013036.2 RefSeqGene

      Range
      4627..869921
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001164749.2 → NP_001158221.1  neuronal PAS domain-containing protein 3 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AB055962, AI811363, AL109769, AL157689, AY157302
      Consensus CDS
      CCDS53891.1
      UniProtKB/Swiss-Prot
      Q86US6, Q86US7, Q8IXF0, Q8IXF2, Q9BY81, Q9H323, Q9Y4L8
      UniProtKB/TrEMBL
      X5D2Q4, X5DNV7
      Related
      ENSP00000348460.4, ENST00000356141.9
      Conserved Domains (5) summary
      smart00091
      Location:152 → 210
      PAS; PAS domain
      cd00083
      Location:52 → 109
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:331 → 413
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:152 → 210
      PAS; PAS fold
      pfam08447
      Location:343 → 430
      PAS_3; PAS fold

    2. NM_001165893.2 → NP_001159365.1  neuronal PAS domain-containing protein 3 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AB054575, AI811363, AL109769, AL157689
      Consensus CDS
      CCDS55912.1
      UniProtKB/TrEMBL
      X5D988, X5DNV7
      Related
      ENSP00000448916.1, ENST00000548645.5
      Conserved Domains (5) summary
      smart00091
      Location:122 → 180
      PAS; PAS domain
      cd00083
      Location:22 → 79
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:301 → 383
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:122 → 180
      PAS; PAS fold
      pfam08447
      Location:313 → 400
      PAS_3; PAS fold

    3. NM_001394988.1 → NP_001381917.1  neuronal PAS domain-containing protein 3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL109769, AL139296, AL157689, AL158802, AL161851
      UniProtKB/TrEMBL
      X5DR67
      Conserved Domains (4) summary
      smart00091
      Location:137 → 195
      PAS; PAS domain
      pfam08447
      Location:328 → 415
      PAS_3; PAS fold
      cd19732
      Location:17 → 94
      bHLH-PAS_NPAS3_PASD6; basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 3 (NPAS3) and similar proteins
      NF033845
      Location:455 → 580
      MSCRAMM_ClfB; MSCRAMM family adhesin clumping factor ClfB

    4. NM_001394989.1 → NP_001381918.1  neuronal PAS domain-containing protein 3 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AL109769, AL139296, AL157689, AL158802, AL161851
      UniProtKB/TrEMBL
      X5D7M0, X5DNV7
      Conserved Domains (4) summary
      smart00091
      Location:122 → 180
      PAS; PAS domain
      pfam08447
      Location:313 → 400
      PAS_3; PAS fold
      cd19732
      Location:17 → 94
      bHLH-PAS_NPAS3_PASD6; basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in neuronal PAS domain-containing protein 3 (NPAS3) and similar proteins
      NF033845
      Location:440 → 562
      MSCRAMM_ClfB; MSCRAMM family adhesin clumping factor ClfB

    5. NM_022123.3 → NP_071406.1  neuronal PAS domain-containing protein 3 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 2, which is shorter than isoform 1.
      Source sequence(s)
      AF164438, AI811363, AL109769, AL157689
      Consensus CDS
      CCDS9645.1
      UniProtKB/TrEMBL
      X5DNV7
      Related
      ENSP00000319610.5, ENST00000346562.6
      Conserved Domains (5) summary
      smart00091
      Location:120 → 178
      PAS; PAS domain
      cd00083
      Location:22 → 79
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:299 → 381
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:120 → 178
      PAS; PAS fold
      pfam08447
      Location:311 → 398
      PAS_3; PAS fold

    6. NM_173159.3 → NP_775182.1  neuronal PAS domain-containing protein 3 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 3, which is shorter than isoform 1.
      Source sequence(s)
      AB054576, AF164438, AI811363, AL109769, AL157689
      Consensus CDS
      CCDS53892.1
      UniProtKB/TrEMBL
      X5DR67
      Related
      ENSP00000350446.5, ENST00000357798.9
      Conserved Domains (5) summary
      smart00091
      Location:139 → 197
      PAS; PAS domain
      cd00083
      Location:22 → 79
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:318 → 400
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:139 → 197
      PAS; PAS fold
      pfam08447
      Location:330 → 417
      PAS_3; PAS fold

    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

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      32934785..33804173
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017021582.2 → XP_016877071.1  neuronal PAS domain-containing protein 3 isoform X1

      UniProtKB/TrEMBL
      F8VR32

    2. XM_017021583.2 → XP_016877072.1  neuronal PAS domain-containing protein 3 isoform X3

      UniProtKB/TrEMBL
      F8VS42

    3. XM_047431678.1 → XP_047287634.1  neuronal PAS domain-containing protein 3 isoform X2

    4. XM_005267991.4 → XP_005268048.2  neuronal PAS domain-containing protein 3 isoform X4

      UniProtKB/TrEMBL
      F8VR32

    5. XM_011537069.3 → XP_011535371.2  neuronal PAS domain-containing protein 3 isoform X6

      UniProtKB/TrEMBL
      F8VS42

    6. XM_017021584.2 → XP_016877073.1  neuronal PAS domain-containing protein 3 isoform X7

      UniProtKB/TrEMBL
      F8VS42

    7. XM_017021585.2 → XP_016877074.1  neuronal PAS domain-containing protein 3 isoform X9

      UniProtKB/TrEMBL
      F8VS42

    8. XM_005267992.4 → XP_005268049.2  neuronal PAS domain-containing protein 3 isoform X5

      UniProtKB/TrEMBL
      F8VR32
      Related
      ENSP00000450392.1, ENST00000551492.5

    9. XM_011537071.3 → XP_011535373.2  neuronal PAS domain-containing protein 3 isoform X10

      UniProtKB/TrEMBL
      F8VS42
      Related
      ENSP00000448373.2, ENST00000551634.6

    10. XM_011537067.3 → XP_011535369.1  neuronal PAS domain-containing protein 3 isoform X8

      UniProtKB/TrEMBL
      X5DR67
      Conserved Domains (5) summary
      smart00091
      Location:169 → 227
      PAS; PAS domain
      cd00083
      Location:52 → 109
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:348 → 430
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:169 → 227
      PAS; PAS fold
      pfam08447
      Location:360 → 447
      PAS_3; PAS fold

    11. XM_047431680.1 → XP_047287636.1  neuronal PAS domain-containing protein 3 isoform X11

    12. XM_017021588.2 → XP_016877077.1  neuronal PAS domain-containing protein 3 isoform X12

      UniProtKB/TrEMBL
      X5D985
      Conserved Domains (4) summary
      smart00091
      Location:50 → 108
      PAS; PAS domain
      cd00130
      Location:229 → 311
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:50 → 108
      PAS; PAS fold
      pfam08447
      Location:241 → 328
      PAS_3; PAS fold

    13. XM_017021587.2 → XP_016877076.1  neuronal PAS domain-containing protein 3 isoform X12

      UniProtKB/TrEMBL
      X5D985
      Conserved Domains (4) summary
      smart00091
      Location:50 → 108
      PAS; PAS domain
      cd00130
      Location:229 → 311
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00989
      Location:50 → 108
      PAS; PAS fold
      pfam08447
      Location:241 → 328
      PAS_3; PAS fold

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      27131685..28001533
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376560.1 → XP_054232535.1  neuronal PAS domain-containing protein 3 isoform X1

    2. XM_054376562.1 → XP_054232537.1  neuronal PAS domain-containing protein 3 isoform X3

    3. XM_054376561.1 → XP_054232536.1  neuronal PAS domain-containing protein 3 isoform X2

    4. XM_054376563.1 → XP_054232538.1  neuronal PAS domain-containing protein 3 isoform X4

    5. XM_054376565.1 → XP_054232540.1  neuronal PAS domain-containing protein 3 isoform X6

    6. XM_054376566.1 → XP_054232541.1  neuronal PAS domain-containing protein 3 isoform X7

    7. XM_054376568.1 → XP_054232543.1  neuronal PAS domain-containing protein 3 isoform X9

    8. XM_054376564.1 → XP_054232539.1  neuronal PAS domain-containing protein 3 isoform X5

    9. XM_054376569.1 → XP_054232544.1  neuronal PAS domain-containing protein 3 isoform X10

    10. XM_054376567.1 → XP_054232542.1  neuronal PAS domain-containing protein 3 isoform X8

    11. XM_054376570.1 → XP_054232545.1  neuronal PAS domain-containing protein 3 isoform X11

    12. XM_054376572.1 → XP_054232547.1  neuronal PAS domain-containing protein 3 isoform X12

    13. XM_054376571.1 → XP_054232546.1  neuronal PAS domain-containing protein 3 isoform X12

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IXF0.1 GenPept UniProtKB/Swiss-Prot:Q8IXF0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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