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    STARD13 StAR related lipid transfer domain containing 13 [ Homo sapiens (human) ]

    Gene ID: 90627, updated on 2-Nov-2024

    Summary

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    Official Symbol
    STARD13provided by HGNC
    Official Full Name
    StAR related lipid transfer domain containing 13provided by HGNC
    Primary source
    HGNC:HGNC:19164
    See related
    Ensembl:ENSG00000133121 MIM:609866; AllianceGenome:HGNC:19164
    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
    DLC2; GT650; ARHGAP37; LINC00464
    Summary
    This gene encodes a protein which contains an N-terminal sterile alpha motif (SAM) for protein-protein interactions, followed by an ATP/GTP-binding motif, a GTPase-activating protein (GAP) domain, and a C-terminal STAR-related lipid transfer (START) domain. It may be involved in regulation of cytoskeletal reorganization, cell proliferation, and cell motility, and acts as a tumor suppressor in hepatoma cells. The gene is located in a region of chromosome 13 that is associated with loss of heterozygosity in hepatocellular carcinomas. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in placenta (RPKM 9.3), thyroid (RPKM 7.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See STARD13 in Genome Data Viewer
    Location:
    13q13.1-q13.2
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (33103137..33676794, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (32320452..32894146, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (33677274..34250931, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene TOMM22 pseudogene 3 Neighboring gene translation initiation factor IF-2-like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:33590741-33591318 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7567 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:33590165-33590740 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:33666443-33666999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7568 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7569 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7570 Neighboring gene klotho Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7572 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr13:33760051-33761250 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7573 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:33770183-33770373 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7574 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7575 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5255 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7576 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:33834523-33835023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7577 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7578 Neighboring gene STARD13 antisense RNA Neighboring gene uncharacterized LOC124903152 Neighboring gene long intergenic non-protein coding RNA 2344 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7579 Neighboring gene NANOG hESC enhancer GRCh37_chr13:33984305-33984872 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:34063621-34064197 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7580 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7581 Neighboring gene uncharacterized LOC102723406 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7582 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7585 Neighboring gene uncharacterized LOC107984551 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5256 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5257 Neighboring gene RNA, U5A small nuclear 4, pseudogene Neighboring gene replication factor C subunit 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
    • 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. MicroRNA-9-5p Facilitates Lung Adenocarcinoma Cell Malignant Progression via Targeting STARD13. Lu Y, et al. Biochem Genet, 2022 Dec. PMID 35119587
    2. DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma. El-Sitt S, et al. Oncol Rep, 2012 Aug. PMID 22614672
    3. Expression of deleted in liver cancer 2 in colorectal cancer and its correlation with clinicopathological parameters. Gao K, et al. Oncol Lett, 2012 Nov. PMID 23162637, Free PMC Article
    4. The STAR of the DLC family. El-Sitt S, et al. J Recept Signal Transduct Res, 2013. PMID 23316797
    5. Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway. Leung TH, et al. Liver Int, 2010 Oct. PMID 20629949

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MicroRNA-9-5p Facilitates Lung Adenocarcinoma Cell Malignant Progression via Targeting STARD13.
      Title: MicroRNA-9-5p Facilitates Lung Adenocarcinoma Cell Malignant Progression via Targeting STARD13.
    2. StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42.
      Title: StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42.
    3. LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis.
      Title: LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis.
    4. Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation.
      Title: Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation.
    5. StarD13 differentially regulates migration and invasion in prostate cancer cells.
      Title: StarD13 differentially regulates migration and invasion in prostate cancer cells.
    6. Identifying Cancer-Relevant Mutations in the DLC START Domain Using Evolutionary and Structure-Function Analyses.
      Title: Identifying Cancer-Relevant Mutations in the DLC START Domain Using Evolutionary and Structure-Function Analyses.
    7. activation of STARD13-correlated ceRNA network was negatively correlated with YAP/TAZ activity in breast cancer.
      Title: STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and Rho-GTPase/F-actin signaling.
    8. DLC2 is abundantly expressed in hepatocellular carcinoma, in which the DLC2 gene is diploid.
      Title: Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma.
    9. Study elucidated StarD13 messenger RNA as a Competitive endogenous messenger RNA (ceRNA) in regulating migration and invasion of breast cancer cells. MicroRNA-125b was identified to induce metastasis of MCF-7 cells and bind with both StarD13 3'UTR and TP53INP1 3'UTR. Therefore, a ceRNA interaction between StarD13 and TP53INP1 mediated by competitively binding to miR-125b was indicated.
      Title: StarD13 3'-untranslated region functions as a ceRNA for TP53INP1 in prohibiting migration and invasion of breast cancer cells by regulating miR-125b activity.
    10. Low STARD13 expression is associated with metastasis of breast cancer.
      Title: STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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 genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.
    EBI GWAS Catalog
    A genome-wide association study of behavioral disinhibition.
    EBI GWAS Catalog
    Genome-wide association study of body mass index in 23 000 individuals with and without asthma.
    EBI GWAS Catalog
    Genome-wide association study of intracranial aneurysm identifies three new risk loci.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ37385

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTPase activator activity TAS
    Traceable Author Statement
    more info
    		  
    enables lipid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in actin cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within endothelial cell migration IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial tube lumen extension IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial tube lumen extension IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of cell migration involved in sprouting angiogenesis IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of cell migration involved in sprouting angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of Rho protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in lipid droplet IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    stAR-related lipid transfer protein 13
    Names
    Rho GTPase activating protein on chromosome 13q12
    StAR-related lipid transfer (START) domain containing 13
    deleted in liver cancer 2 protein
    long intergenic non-protein coding RNA 464

    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_029752.2 RefSeqGene

      Range
      396081..578699
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243466.2 → NP_001230395.1  stAR-related lipid transfer protein 13 isoform 5

      See identical proteins and their annotated locations for NP_001230395.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate 5' terminal exon, and differs at the 3' end compared to variant 1. This results in a shorter isoform (5) with distinct N- and C- termini compared to isoform 1.
      Source sequence(s)
      AK308453, AL139187, BC046563
      UniProtKB/TrEMBL
      B3KRK6
      Conserved Domains (2) summary
      cd09592
      Location:49 → 112
      SAM_DLC2; SAM domain of STARD13-like subfamily
      cl02570
      Location:649 → 686
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    2. NM_001243474.2 → NP_001230403.1  stAR-related lipid transfer protein 13 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate 5' terminal exon, and differs at the 3' end compared to variant 1. This results in translation initiation from an in-frame downstream AUG, and an isoform (6) with a shorter N-terminus, and a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AK091804, AK308453, BC046563, BP233049
      UniProtKB/TrEMBL
      B3KRK6
      Conserved Domains (1) summary
      cl02570
      Location:539 → 642
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    3. NM_001243476.3 → NP_001230405.1  stAR-related lipid transfer protein 13 isoform 4

      See identical proteins and their annotated locations for NP_001230405.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks a portion of the 5' coding region and contains multiple alternate 5' exons, and initiates initiates translation at an alternate start codon, compared to variant 1. This results in a shorter isoform (4) with a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AA256386, AK308453, AY082589, BX647695, CB163673, DA312208, DB449764
      UniProtKB/Swiss-Prot
      Q9Y3M8
      Conserved Domains (3) summary
      cd08909
      Location:865 → 1069
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd09592
      Location:22 → 85
      SAM_DLC2; SAM domain of STARD13-like subfamily
      cd04375
      Location:622 → 839
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    4. NM_001411014.1 → NP_001397943.1  stAR-related lipid transfer protein 13 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AL138999, AL139187
      Consensus CDS
      CCDS91800.1
      UniProtKB/TrEMBL
      H3BRG5
      Related
      ENSP00000456233.2, ENST00000567873.2

    5. NM_052851.3 → NP_443083.1  stAR-related lipid transfer protein 13 isoform 3

      See identical proteins and their annotated locations for NP_443083.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame downstream AUG, and an isoform (3, also known as DLC2gamma) with a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AA256386, AL049801, AY082590, AY082591, AY366448, BP233049, CB163673
      Consensus CDS
      CCDS9350.1
      UniProtKB/TrEMBL
      B2R789
      Related
      ENSP00000382300.3, ENST00000399365.7
      Conserved Domains (2) summary
      cd08909
      Location:782 → 986
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd04375
      Location:539 → 756
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    6. NM_178006.4 → NP_821074.1  stAR-related lipid transfer protein 13 isoform 1

      See identical proteins and their annotated locations for NP_821074.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1, also known as DLC2alpha).
      Source sequence(s)
      AA256386, AY082589, AY082590, AY366448, CB163673, DC402824
      Consensus CDS
      CCDS9348.1
      UniProtKB/Swiss-Prot
      A2A309, A2A310, Q5HYH1, Q5TAE3, Q6UN61, Q86TP6, Q86WQ3, Q86XT1, Q9Y3M8
      Related
      ENSP00000338785.4, ENST00000336934.10
      Conserved Domains (4) summary
      cd08909
      Location:900 → 1104
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd09592
      Location:57 → 120
      SAM_DLC2; SAM domain of STARD13-like subfamily
      smart00454
      Location:61 → 120
      SAM; Sterile alpha motif
      cd04375
      Location:657 → 874
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    7. NM_178007.3 → NP_821075.1  stAR-related lipid transfer protein 13 isoform 2

      See identical proteins and their annotated locations for NP_821075.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. This results in a shorter isoform (2, also known as DLC2beta) with a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AA256386, AL139187, AY082590, AY366448, CB163673
      Consensus CDS
      CCDS9349.1
      UniProtKB/Swiss-Prot
      Q9Y3M8
      Related
      ENSP00000255486.4, ENST00000255486.8
      Conserved Domains (4) summary
      cd08909
      Location:892 → 1096
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd09592
      Location:49 → 112
      SAM_DLC2; SAM domain of STARD13-like subfamily
      smart00454
      Location:53 → 112
      SAM; Sterile alpha motif
      cd04375
      Location:649 → 866
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    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_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      33103137..33676794 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020835.3 → XP_016876324.1  stAR-related lipid transfer protein 13 isoform X2

      Conserved Domains (3) summary
      cd08909
      Location:865 → 1069
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd09592
      Location:22 → 85
      SAM_DLC2; SAM domain of STARD13-like subfamily
      cd04375
      Location:622 → 839
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    2. XM_047430759.1 → XP_047286715.1  stAR-related lipid transfer protein 13 isoform X1

    3. XM_024449429.2 → XP_024305197.1  stAR-related lipid transfer protein 13 isoform X2

      Conserved Domains (3) summary
      cd08909
      Location:865 → 1069
      START_STARD13-like; C-terminal lipid-binding START domain of mammalian STARD13 and related proteins, which also have an N-terminal Rho GTPase-activating protein (RhoGAP) domain
      cd09592
      Location:22 → 85
      SAM_DLC2; SAM domain of STARD13-like subfamily
      cd04375
      Location:622 → 839
      RhoGAP_DLC1; RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a ...

    4. XM_047430760.1 → XP_047286716.1  stAR-related lipid transfer protein 13 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      32320452..32894146 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375159.1 → XP_054231134.1  stAR-related lipid transfer protein 13 isoform X2

    2. XM_054375157.1 → XP_054231132.1  stAR-related lipid transfer protein 13 isoform X1

    3. XM_054375158.1 → XP_054231133.1  stAR-related lipid transfer protein 13 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_178008.1: Suppressed sequence

      Description
      NM_178008.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y3M8.2 GenPept UniProtKB/Swiss-Prot:Q9Y3M8

    Gene LinkOut

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

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