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    STAC3 SH3 and cysteine rich domain 3 [ Homo sapiens (human) ]

    Gene ID: 246329, updated on 27-Nov-2024

    Summary

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    Official Symbol
    STAC3provided by HGNC
    Official Full Name
    SH3 and cysteine rich domain 3provided by HGNC
    Primary source
    HGNC:HGNC:28423
    See related
    Ensembl:ENSG00000185482 MIM:615521; AllianceGenome:HGNC:28423
    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
    NAM; MYPBB; CMYO13; CMYP13
    Summary
    The protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles. This protein is a member of the Stac gene family and contains an N-terminal cysteine-rich domain and two SH3 domains. Mutations in this gene are a cause of Native American myopathy. [provided by RefSeq, Nov 2013]
    Expression
    Biased expression in prostate (RPKM 23.6), esophagus (RPKM 13.8) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See STAC3 in Genome Data Viewer
    Location:
    12q13.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (57243458..57251187, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (57211695..57219414, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (57637241..57644970, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57609975-57610474 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57610622-57611230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57611231-57611837 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57617093-57617999 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6528 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6529 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6530 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57624967-57625547 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57625548-57626129 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57626711-57627291 Neighboring gene Sharpr-MPRA regulatory region 225 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6532 Neighboring gene neurexophilin 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57631624-57632226 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4579 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57633295-57634200 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr12:57636011-57636914 Neighboring gene NDUFA4 mitochondrial complex associated like 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6534 Neighboring gene serine hydroxymethyltransferase 2 Neighboring gene Sharpr-MPRA regulatory region 5413 Neighboring gene R3H domain containing 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:57673563-57674762 Neighboring gene Sharpr-MPRA regulatory region 11351 Neighboring gene Sharpr-MPRA regulatory region 7317 Neighboring gene MPRA-validated peak1746 silencer Neighboring gene RNA, U6 small nuclear 879, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6535 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4580 Neighboring gene R3HDM2 divergent transcript

    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. STAC3 related congenital myopathy: A case series of seven Comorian patients. Gromand M, et al. Eur J Med Genet, 2022 Oct. PMID 36030003
    2. Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. Telegrafi A, et al. Am J Med Genet A, 2017 Oct. PMID 28777491, Free PMC Article
    3. Multiple Sequence Variants in STAC3 Affect Interactions with Ca(V)1.1 and Excitation-Contraction Coupling. Rufenach B, et al. Structure, 2020 Aug 4. PMID 32492370
    4. STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility. Zaharieva IT, et al. Hum Mutat, 2018 Dec. PMID 30168660
    5. [When all roads lead to Africa…]. Urtizberea JA, et al. Med Sci (Paris), 2019 Nov. PMID 31859625

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR processing.
      Title: Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR processing.
    2. STAC3 related congenital myopathy: A case series of seven Comorian patients.
      Title: STAC3 related congenital myopathy: A case series of seven Comorian patients.
    3. Multiple Sequence Variants in STAC3 Affect Interactions with CaV1.1 and Excitation-Contraction Coupling.
      Title: Multiple Sequence Variants in STAC3 Affect Interactions with Ca(V)1.1 and Excitation-Contraction Coupling.
    4. Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Bayesian method provides new approach to predict MH pathogenicity of genetic variants
      Title: Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants.
    5. Unexpected discoveries in the case reported here in a Kuwaiti family, via Next Generation Sequencing, identifying the STAC3 mutation as the underlying cause of a Native American Myopathy phenotype.
      Title: [When all roads lead to Africa…].
    6. recent identification of the adaptor protein STAC3 as fourth essential component of skeletal muscle EC coupling prompted vigorous research to reveal its role in this signaling process.
      Title: STAC proteins: The missing link in skeletal muscle EC coupling and new regulators of calcium channel function.
    7. Study reports patients with congenital myopathy carrying either a homozygous, heterozygous p.(Trp284Ser) STAC3 variant or a novel splice site change (c.997-1G > T). The patients have distinctive dysmorphic features in addition to a malignant hyperthermia-like in some. These variants showed a defective excitation-contraction which is not a result of CaV 1.1 sarcolemma mislocation or impaired interaction with CaV 1.1.
      Title: STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.
    8. STAC3 mutation is associated with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.
      Title: Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.
    9. A mutation in human STAC3 is the genetic basis of the debilitating Native American myopathy.
      Title: Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy.
    Submit: New GeneRIF Correction

    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

    Associated conditions

    Description Tests
    Bailey-Bloch congenital myopathy
    MedGen: C1850625 OMIM: 255995 GeneReviews: STAC3 Disorder
    		Compare labs

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic 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

    • MGC2793

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion 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 neuromuscular synaptic transmission IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of protein localization to plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of protein localization to plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of voltage-gated calcium channel activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in skeletal muscle contraction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in skeletal muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in skeletal muscle fiber development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in T-tubule IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasmic side of plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of voltage-gated calcium channel complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    SH3 and cysteine-rich domain-containing protein 3

    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_033835.1 RefSeqGene

      Range
      5007..12736
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001286256.2 → NP_001273185.1  SH3 and cysteine-rich domain-containing protein 3 isoform b

      See identical proteins and their annotated locations for NP_001273185.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus than isoform a.
      Source sequence(s)
      BC008069, DA896836
      Consensus CDS
      CCDS66406.1
      UniProtKB/Swiss-Prot
      Q96MF2
      Related
      ENSP00000452068.1, ENST00000554578.5
      Conserved Domains (4) summary
      cd11834
      Location:271 → 321
      SH3_Stac_2; Second C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing proteins 1 and 3
      cd11986
      Location:212 → 264
      SH3_Stac3_1; First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3)
      pfam00130
      Location:51 → 96
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
      pfam16664
      Location:108 → 200
      STAC2_u1; Unstructured on SH3 and cysteine-rich domain-containing protein 2

    2. NM_001286257.2 → NP_001273186.1  SH3 and cysteine-rich domain-containing protein 3 isoform c

      See identical proteins and their annotated locations for NP_001273186.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) has a shorter N-terminus than isoform a.
      Source sequence(s)
      AK300688, BC008069, DA896836
      Consensus CDS
      CCDS66405.1
      UniProtKB/Swiss-Prot
      Q96MF2
      Related
      ENSP00000441515.2, ENST00000546246.2
      Conserved Domains (2) summary
      cd11834
      Location:124 → 174
      SH3_Stac_2; Second C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing proteins 1 and 3
      cl17036
      Location:65 → 117
      SH3; Src Homology 3 domain superfamily

    3. NM_145064.3 → NP_659501.1  SH3 and cysteine-rich domain-containing protein 3 isoform a

      See identical proteins and their annotated locations for NP_659501.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AK057013, BU738507, DA896836
      Consensus CDS
      CCDS8936.1
      UniProtKB/Swiss-Prot
      B4DUK9, Q96HU5, Q96MF2
      Related
      ENSP00000329200.2, ENST00000332782.7
      Conserved Domains (4) summary
      cd11834
      Location:310 → 360
      SH3_Stac_2; Second C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing proteins 1 and 3
      cd11986
      Location:251 → 303
      SH3_Stac3_1; First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3)
      pfam00130
      Location:90 → 135
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
      pfam16664
      Location:147 → 239
      STAC2_u1; Unstructured on SH3 and cysteine-rich domain-containing protein 2

    RNA

    1. NR_104422.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks four alternate internal exons, compared to variant 1. This variant is represented as non-coding because the use of the expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK057013, AK311513, BC008069, DA896836
      Related
      ENST00000557176.5

    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
      57243458..57251187 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538126.3 → XP_011536428.1  SH3 and cysteine-rich domain-containing protein 3 isoform X1

      See identical proteins and their annotated locations for XP_011536428.1

      UniProtKB/Swiss-Prot
      B4DUK9, Q96HU5, Q96MF2
      Conserved Domains (4) summary
      cd11834
      Location:310 → 360
      SH3_Stac_2; Second C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing proteins 1 and 3
      cd11986
      Location:251 → 303
      SH3_Stac3_1; First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3)
      pfam00130
      Location:90 → 135
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
      pfam16664
      Location:147 → 239
      STAC2_u1; Unstructured on SH3 and cysteine-rich domain-containing protein 2

    2. XM_047428657.1 → XP_047284613.1  SH3 and cysteine-rich domain-containing protein 3 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      57211695..57219414 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371649.1 → XP_054227624.1  SH3 and cysteine-rich domain-containing protein 3 isoform X1

      UniProtKB/Swiss-Prot
      B4DUK9, Q96HU5, Q96MF2

    2. XM_054371650.1 → XP_054227625.1  SH3 and cysteine-rich domain-containing protein 3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96MF2.1 GenPept UniProtKB/Swiss-Prot:Q96MF2

    Gene LinkOut

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

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