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    RPH3A rabphilin 3A [ Homo sapiens (human) ]

    Gene ID: 22895, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RPH3Aprovided by HGNC
    Official Full Name
    rabphilin 3Aprovided by HGNC
    Primary source
    HGNC:HGNC:17056
    See related
    Ensembl:ENSG00000089169 MIM:612159; AllianceGenome:HGNC:17056
    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
    Summary
    The protein encoded by this gene is thought to be an effector for RAB3A, which is a small G protein that acts in the late stages of neurotransmitter exocytosis. The encoded protein may be involved in neurotransmitter release and synaptic vesicle traffic. [provided by RefSeq, Dec 2016]
    Expression
    Biased expression in brain (RPKM 30.1) and adrenal (RPKM 1.7) See more
    Orthologs
    mouse all
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    Genomic context

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    See RPH3A in Genome Data Viewer
    Location:
    12q24.13
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (112575236..112898881)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (112552138..112875587)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (113013040..113336686)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903023 Neighboring gene protein tyrosine phosphatase non-receptor type 11 Neighboring gene uncharacterized LOC124903024 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112954684-112955184 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:113015949-113016468 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113018366-113018890 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:113039985-113040713 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:113055106-113055606 Neighboring gene NANOG hESC enhancer GRCh37_chr12:113079622-113080142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113147969-113148469 Neighboring gene microRNA 1302-1 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr12:113185662-113186162 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113229645-113230186 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:113306366-113306564 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7052 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24142 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24146 and experimental_24152 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24159 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24163 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24171 and experimental_24176 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24264 and experimental_24270 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24215 and experimental_24231 Neighboring gene Sharpr-MPRA regulatory region 3381 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24293 and experimental_24295 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24298, experimental_24301 and experimental_24306 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24317/24320 and experimental_24338 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24357 and experimental_24368 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24404 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24448 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24456 and experimental_24461 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24463 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24487 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7053 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24505 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4887 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24515 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24520 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24535 Neighboring gene MPRA-validated peak1965 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113400746-113401246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113401247-113401747 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24547 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24553 Neighboring gene 2'-5'-oligoadenylate synthetase 1 Neighboring gene 2'-5'-oligoadenylate synthetase 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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    Related articles in PubMed

    1. Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder. Pavinato L, et al. Genet Med, 2023 Nov. PMID 37403762
    2. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Kirov G, et al. Mol Psychiatry, 2012 Feb. PMID 22083728, Free PMC Article
    3. Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden. Tan MG, et al. Neurochem Int, 2014 Jan. PMID 24200817
    4. Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. Iwama S, et al. J Clin Endocrinol Metab, 2015 Jul. PMID 25919460, Free PMC Article
    5. Clinical significance of a novel single nucleotide polymorphism in the 5' untranslated region of the Rabphillin-3A-Like gene in colorectal adenocarcinoma. Katkoori VR, et al. Front Biosci, 2008 Jan 1. PMID 17981610, Free PMC Article

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder.
      Title: Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder.
    2. Protein and fat intake interacts with the haplotype of PTPN11_rs11066325, RPH3A_rs886477, and OAS3_rs2072134 to modulate serum HDL concentrations in middle-aged people.
      Title: Protein and fat intake interacts with the haplotype of PTPN11_rs11066325, RPH3A_rs886477, and OAS3_rs2072134 to modulate serum HDL concentrations in middle-aged people.
    3. Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization.
      Title: Small GTPase ARF6 Is a Coincidence-Detection Code for RPH3A Polarization in Neutrophil Polarization.
    4. Rab27/Rabphilin3a/GRAB/Rab3 constitutes a signaling module in sperm exocytosis.
      Title: Grab recruitment by Rab27A-Rabphilin3a triggers Rab3A activation in human sperm exocytosis.
    5. Findings indicate that Rph3A activity is linked to the aberrant synaptic localization of GluN2A-expressing NMDARs characterizing levodopa-induced dyskinesias; suggest that Rph3A/GluN2A complex could represent an innovative therapeutic target for those pathological conditions where NMDAR composition is significantly altered.
      Title: Rabphilin 3A: A novel target for the treatment of levodopa-induced dyskinesias.
    6. Rabphilin-3A is a major autoantigen in Lymphocytic infundibulo-neurohypophysitis (LINH). Autoantibodies to rabphilin-3A may serve as biomarker for the diagnosis of LINH and be useful for the differential diagnosis of Central diabetes insipidus.
      Title: Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis.
    7. rabphilin 3A loss correlated with dementia severity, cholinergic deafferentation, and increased beta-amyloid concentrations
      Title: Decreased rabphilin 3A immunoreactivity in Alzheimer's disease is associated with Aβ burden.
    8. Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.
      Title: Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.
    9. We found a reduction in rabphilin 3a, a protein involved in vesicle docking and recycling, in Huntington disease[HD] brains of grade III and IV. A deficient pre-synaptic transmitter release may underlie some symptoms of HD.
      Title: Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington's disease.
    10. Rabphilin-3A and Rab3A are present in normal mouse, rat, and human kidneys, with an exclusively glomerular expression and a comma-like pattern of positivity along the glomerular capillary wall, suggestive for podocyte staining.
      Title: Glomerular podocytes possess the synaptic vesicle molecule Rab3A and its specific effector rabphilin-3a.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2018-07-25)

    ClinGen Genome Curation Page
    Haploinsufficency

    Little evidence for dosage pathogenicity (Last evaluated 2018-07-25)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    New gene functions in megakaryopoiesis and platelet formation.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0985

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables calcium-dependent phospholipid binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables inositol 1,4,5 trisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphate ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol phosphate binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables phosphatidylinositol-4,5-bisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-containing complex binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables selenium binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables small GTPase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in calcium-dependent activation of synaptic vesicle fusion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of calcium ion-dependent exocytosis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in synaptic vesicle priming IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    colocalizes_with Golgi apparatus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in dendritic spine IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extrinsic component of membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in extrinsic component of synaptic vesicle membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in neuron projection IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in neuron projection ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in postsynaptic membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of protein-containing complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in secretory granule ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in synaptic vesicle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in synaptic vesicle membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    rabphilin-3A
    Names
    exophilin-1
    rabphilin 3A homolog

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_052871.1 RefSeqGene

      Range
      221652..328785
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001143854.2 → NP_001137326.1  rabphilin-3A isoform 1

      See identical proteins and their annotated locations for NP_001137326.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 3, 4, and 5 all encode the same isoform (1).
      Source sequence(s)
      AB023202, BU738474, DA332963
      Consensus CDS
      CCDS44979.1
      UniProtKB/Swiss-Prot
      B7Z3C3, Q96AE0, Q9Y2J0
      UniProtKB/TrEMBL
      B7Z9Z7
      Related
      ENSP00000374036.4, ENST00000389385.9
      Conserved Domains (3) summary
      cd04035
      Location:393 → 516
      C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
      cd08384
      Location:553 → 685
      C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain
      cd15762
      Location:92 → 171
      FYVE_RP3A; FYVE-related domain found in rabphilin-3A and similar proteins

    2. NM_001347952.2 → NP_001334881.1  rabphilin-3A isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 3, 4, and 5 all encode the same isoform (1).
      Source sequence(s)
      AC004216, AC004465, AC004551
      Consensus CDS
      CCDS44979.1
      UniProtKB/Swiss-Prot
      B7Z3C3, Q96AE0, Q9Y2J0
      UniProtKB/TrEMBL
      B7Z9Z7
      Related
      ENSP00000440384.2, ENST00000543106.6

    3. NM_001347953.1 → NP_001334882.1  rabphilin-3A isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 3, 4, and 5 all encode the same isoform (1).
      Source sequence(s)
      AC004465, AC004551
      Consensus CDS
      CCDS44979.1
      UniProtKB/Swiss-Prot
      B7Z3C3, Q96AE0, Q9Y2J0
      UniProtKB/TrEMBL
      B7Z9Z7
      Related
      ENSP00000405357.3, ENST00000415485.7

    4. NM_001347954.2 → NP_001334883.1  rabphilin-3A isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 3, 4, and 5 all encode the same isoform (1).
      Source sequence(s)
      AC004465, AC004551
      Consensus CDS
      CCDS44979.1
      UniProtKB/Swiss-Prot
      B7Z3C3, Q96AE0, Q9Y2J0
      UniProtKB/TrEMBL
      B7Z9Z7

    5. NM_001347955.2 → NP_001334884.1  rabphilin-3A isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AC004465, AC004551
      UniProtKB/TrEMBL
      F8VP47

    6. NM_014954.4 → NP_055769.2  rabphilin-3A isoform 2

      See identical proteins and their annotated locations for NP_055769.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 4 aa shorter compared to isoform 1.
      Source sequence(s)
      AB023202, BU738474, DA332963
      Consensus CDS
      CCDS31904.1
      UniProtKB/TrEMBL
      B7Z9Z7
      Related
      ENSP00000448297.1, ENST00000551052.5
      Conserved Domains (4) summary
      cd04035
      Location:389 → 512
      C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
      cd08384
      Location:549 → 681
      C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain
      cd15762
      Location:88 → 167
      FYVE_RP3A; FYVE-related domain found in rabphilin-3A and similar proteins
      cl26386
      Location:165 → 349
      DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III

    RNA

    1. NR_145126.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC004465, AC004551

    2. NR_145127.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC004465, AC004551

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      112575236..112898881
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047428540.1 → XP_047284496.1  rabphilin-3A isoform X1

    2. XM_017019034.3 → XP_016874523.1  rabphilin-3A isoform X2

      Conserved Domains (2) summary
      cd04035
      Location:45 → 168
      C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
      cd08384
      Location:205 → 337
      C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      112552138..112875587
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371454.1 → XP_054227429.1  rabphilin-3A isoform X3

      UniProtKB/Swiss-Prot
      B7Z3C3, Q96AE0, Q9Y2J0

    2. XM_054371455.1 → XP_054227430.1  rabphilin-3A isoform X1

    3. XM_054371456.1 → XP_054227431.1  rabphilin-3A isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y2J0.1 GenPept UniProtKB/Swiss-Prot:Q9Y2J0

    Gene LinkOut

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

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