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SH2B3 SH2B adaptor protein 3 [ Homo sapiens (human) ]

Gene ID: 10019, updated on 11-Apr-2024

Summary

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Official Symbol
SH2B3provided by HGNC
Official Full Name
SH2B adaptor protein 3provided by HGNC
Primary source
HGNC:HGNC:29605
See related
Ensembl:ENSG00000111252 MIM:605093; AllianceGenome:HGNC:29605
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
LNK; IDDM20
Summary
This gene encodes a member of the SH2B adaptor family of proteins, which are involved in a range of signaling activities by growth factor and cytokine receptors. The encoded protein is a key negative regulator of cytokine signaling and plays a critical role in hematopoiesis. Mutations in this gene have been associated with susceptibility to celiac disease type 13 and susceptibility to insulin-dependent diabetes mellitus. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
Expression
Ubiquitous expression in bone marrow (RPKM 12.8), spleen (RPKM 12.6) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
12q24.12
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (111404730..111451623)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (111385588..111432181)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (111843727..111889427)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111799560-111800216 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4865 Neighboring gene long intergenic non-protein coding RNA 2356 Neighboring gene PH domain containing endocytic trafficking adaptor 1 Neighboring gene heat shock protein family A (Hsp70) member 8 pseudogene 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7031 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4866 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4867 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111851003-111851850 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111855471-111856170 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111863315-111863890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7032 Neighboring gene uncharacterized LOC124903019 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7033 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7034 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111873559-111874138 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111874139-111874718 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:111876422-111876935 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:111877948-111878492 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:111880447-111880633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7035 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7036 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7037 Neighboring gene ataxin 2 Neighboring gene U7 small nuclear RNA Neighboring gene ReSE screen-validated silencer GRCh37_chr12:112008371-112008568 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4869 Neighboring gene IFITM3 pseudogene 5

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. Acquired uniparental isodisomies involving chromosome 12 in paediatric B-cell precursor acute lymphoblastic leukaemia: Associations with chromosome 21 gains and SH2B3 mutations. Lundin-Ström KB, et al. Br J Haematol, 2023 May. PMID 36899493
  2. Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels. Mo X, et al. Rheumatology (Oxford), 2020 Apr 1. PMID 31624844
  3. The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects. Kuo CL, et al. J Gerontol A Biol Sci Med Sci, 2020 Sep 16. PMID 31428775, Free PMC Article
  4. Germline SH2B3 pathogenic variant associated with myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. Coltro G, et al. Am J Hematol, 2019 Sep. PMID 31173385
  5. SH2B3 inactivation through CN-LOH 12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain. Sinclair PB, et al. Leukemia, 2019 Aug. PMID 30816328, Free PMC Article

See all (116) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.
    Title: Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity.
  2. Acquired uniparental isodisomies involving chromosome 12 in paediatric B-cell precursor acute lymphoblastic leukaemia: Associations with chromosome 21 gains and SH2B3 mutations.
    Title: Acquired uniparental isodisomies involving chromosome 12 in paediatric B-cell precursor acute lymphoblastic leukaemia: Associations with chromosome 21 gains and SH2B3 mutations.
  3. CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.
    Title: CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.
  4. The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.
    Title: The Autoimmune Risk R262W Variant of the Adaptor SH2B3 Improves Survival in Sepsis.
  5. LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway.
    Title: LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway.
  6. The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects.
    Title: The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects.
  7. Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures.
    Title: Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures.
  8. Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels.
    Title: Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels.
  9. The requirement of PI3K-Akt activation for the cardioprotective effect of Lnk was confirmed.
    Title: The lymphocyte adapter protein: A negative regulator of myocardial ischemia/reperfusion injury.
  10. LNK as an adaptor protein had low expression in colorectal cancer.
    Title: LNK protein: Low expression in human colorectal carcinoma and relationship with tumor invasion.
Submit: New GeneRIF Correction See all GeneRIFs (69)

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
Primary familial polycythemia due to EPO receptor mutation
MedGen: C4551637 OMIM: 133100 GeneReviews: Primary Familial and Congenital Polycythemia
Compare labs
Primary myelofibrosis
MedGen: C0001815 OMIM: 254450 GeneReviews: Not available
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Thrombocythemia 1
MedGen: C3277671 OMIM: 187950 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.
EBI GWAS Catalog
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.
EBI GWAS Catalog
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
EBI GWAS Catalog
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
EBI GWAS Catalog
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.
EBI GWAS Catalog
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
EBI GWAS Catalog
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
EBI GWAS Catalog
Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
EBI GWAS Catalog
Genome-wide association study identifies eight loci associated with blood pressure.
EBI GWAS Catalog
Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.
EBI GWAS Catalog
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
EBI GWAS Catalog
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
EBI GWAS Catalog
Genome-wide association study of blood pressure and hypertension.
EBI GWAS Catalog
Genome-wide association study of hematological and biochemical traits in a Japanese population.
EBI GWAS Catalog
Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.
EBI GWAS Catalog
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
EBI GWAS Catalog
Multiple common variants for celiac disease influencing immune gene expression.
EBI GWAS Catalog
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
EBI GWAS Catalog
New gene functions in megakaryopoiesis and platelet formation.
EBI GWAS Catalog
Newly identified genetic risk variants for celiac disease related to the immune response.
EBI GWAS Catalog
Novel associations for hypothyroidism include known autoimmune risk loci.
EBI GWAS Catalog
Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction.
EBI GWAS Catalog
Seventy-five genetic loci influencing the human red blood cell.
EBI GWAS Catalog
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
EBI GWAS Catalog
The ATXN2-SH2B3 locus is associated with peripheral arterial disease: an electronic medical record-based genome-wide association study.
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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein tyrosine kinase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables signaling receptor complex adaptor activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables stem cell factor receptor binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables transmembrane receptor protein tyrosine kinase adaptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in cell surface receptor protein tyrosine kinase signaling pathway IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within_negative_effect cellular response to chemokine ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to interleukin-3 ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_negative_effect embryonic hemopoiesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in erythrocyte development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in hematopoietic stem cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in megakaryocyte development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in monocyte homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in negative regulation of Kit signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of MAPK cascade ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of cell population proliferation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of chemokine-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of platelet aggregation ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in negative regulation of receptor signaling pathway via JAK-STAT IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of receptor signaling pathway via STAT ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of response to cytokine stimulus IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in neutrophil homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
acts_upstream_of_or_within_negative_effect thrombopoietin-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in thrombopoietin-mediated signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within_negative_effect thrombopoietin-mediated signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
SH2B adapter protein 3
Names
lymphocyte-specific adapter protein Lnk
signal transduction protein Lnk

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_021216.1 RefSeqGene

    Range
    5001..50676
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_621

mRNA and Protein(s)

  1. NM_001291424.1 → NP_001278353.1  SH2B adapter protein 3 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks two alternate exons in the 5' region, including a portion of the 5' coding region, and initiates translation at an alternate start codon in an alternate exon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AB208911, AK302173, BC015786, BC136451
    Consensus CDS
    CCDS76602.1
    UniProtKB/TrEMBL
    B7Z7K6, F5GYM4
    Related
    ENSP00000440597.1, ENST00000538307.1
    Conserved Domains (2) summary
    cd10412
    Location:153 → 249
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cl17171
    Location:1 → 107
    PH-like; Pleckstrin homology-like domain

  2. NM_005475.3 → NP_005466.1  SH2B adapter protein 3 isoform 1

    See identical proteins and their annotated locations for NP_005466.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AB208911, AC005805, AF055581
    Consensus CDS
    CCDS9153.1
    UniProtKB/Swiss-Prot
    B9EGG5, O95184, Q9UQQ2
    Related
    ENSP00000345492.2, ENST00000341259.7
    Conserved Domains (3) summary
    cd10412
    Location:355 → 451
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:194 → 309
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:25 → 80
    Phe_ZIP; Phenylalanine zipper

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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
    111404730..111451623
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011537720.4 → XP_011536022.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_011536022.1

    Conserved Domains (3) summary
    cd10412
    Location:396 → 492
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:194 → 349
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:25 → 80
    Phe_ZIP; Phenylalanine zipper

  2. XM_047428025.1 → XP_047283981.1  SH2B adapter protein 3 isoform X2

  3. XM_047428026.1 → XP_047283982.1  SH2B adapter protein 3 isoform X4

    UniProtKB/Swiss-Prot
    B9EGG5, O95184, Q9UQQ2

  4. XM_011537719.3 → XP_011536021.1  SH2B adapter protein 3 isoform X1

    See identical proteins and their annotated locations for XP_011536021.1

    Conserved Domains (3) summary
    cd10412
    Location:396 → 492
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:194 → 349
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:25 → 80
    Phe_ZIP; Phenylalanine zipper

  5. XM_005253818.5 → XP_005253875.1  SH2B adapter protein 3 isoform X2

    Conserved Domains (3) summary
    cd10412
    Location:395 → 491
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:194 → 349
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:25 → 80
    Phe_ZIP; Phenylalanine zipper

  6. XM_005253819.5 → XP_005253876.1  SH2B adapter protein 3 isoform X3

    Conserved Domains (3) summary
    cd10412
    Location:356 → 452
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cd01231
    Location:194 → 309
    PH_SH2B_family; SH2B adapter protein 1, 2, and 3 Pleckstrin homology (PH) domain
    pfam08916
    Location:25 → 80
    Phe_ZIP; Phenylalanine zipper

  7. XM_047428027.1 → XP_047283983.1  SH2B adapter protein 3 isoform X5

  8. XM_047428028.1 → XP_047283984.1  SH2B adapter protein 3 isoform X7

  9. XM_006719180.5 → XP_006719243.1  SH2B adapter protein 3 isoform X6

    UniProtKB/TrEMBL
    B7Z7K6
    Conserved Domains (2) summary
    cd10412
    Location:89 → 185
    SH2_SH2B3; Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3)
    cl17171
    Location:1 → 42
    PH-like; Pleckstrin homology-like domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    111385588..111432181
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054370694.1 → XP_054226669.1  SH2B adapter protein 3 isoform X4

  2. XM_054370690.1 → XP_054226665.1  SH2B adapter protein 3 isoform X1

  3. XM_054370692.1 → XP_054226667.1  SH2B adapter protein 3 isoform X2

  4. XM_054370689.1 → XP_054226664.1  SH2B adapter protein 3 isoform X1

  5. XM_054370691.1 → XP_054226666.1  SH2B adapter protein 3 isoform X2

  6. XM_054370693.1 → XP_054226668.1  SH2B adapter protein 3 isoform X3

  7. XM_054370695.1 → XP_054226670.1  SH2B adapter protein 3 isoform X5

  8. XM_054370697.1 → XP_054226672.1  SH2B adapter protein 3 isoform X7

  9. XM_054370696.1 → XP_054226671.1  SH2B adapter protein 3 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UQQ2.2 GenPept UniProtKB/Swiss-Prot:Q9UQQ2

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