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 susceptibi... See more...

Aliases for SH2B3 Gene

Aliases for SH2B3 Gene

  • SH2B Adaptor Protein 3 2 3 5
  • Lymphocyte-Specific Adapter Protein Lnk 3 4
  • Signal Transduction Protein Lnk 3 4
  • SH2B Adapter Protein 3 3 4
  • LNK 3 4
  • Lymphocyte Adapter Protein 4
  • Lymphocyte Adaptor Protein 2
  • IDDM20 3

External Ids for SH2B3 Gene

Previous GeneCards Identifiers for SH2B3 Gene

  • GC12P110328
  • GC12P111843
  • GC12P108858

Summaries for SH2B3 Gene

Entrez Gene Summary for SH2B3 Gene

  • 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]

CIViC Summary for SH2B3 Gene

GeneCards Summary for SH2B3 Gene

SH2B3 (SH2B Adaptor Protein 3) is a Protein Coding gene. Diseases associated with SH2B3 include Erythrocytosis, Familial, 1 and Thrombocythemia 1. Among its related pathways are T cell receptor signaling pathway and Development HGF signaling pathway. Gene Ontology (GO) annotations related to this gene include obsolete signal transducer activity and phosphate ion binding. An important paralog of this gene is SH2B2.

UniProtKB/Swiss-Prot Summary for SH2B3 Gene

  • Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.

Gene Wiki entry for SH2B3 Gene

Additional gene information for SH2B3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SH2B3 Gene

Genomics for SH2B3 Gene

GeneHancer (GH) Regulatory Elements for SH2B3 Gene

Promoters and enhancers for SH2B3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SH2B3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SH2B3 gene promoter:
  • AP-4
  • c-Ets-1
  • Ik-3
  • LCR-F1
  • MyoD
  • NF-AT1
  • SRF
  • STAT3
  • STAT5A

Genomic Locations for SH2B3 Gene

Genomic Locations for SH2B3 Gene
chr12:111,405,108-111,451,624
(GRCh38/hg38)
Size:
46,517 bases
Orientation:
Plus strand
chr12:111,843,752-111,889,427
(GRCh37/hg19)
Size:
45,676 bases
Orientation:
Plus strand

Genomic View for SH2B3 Gene

Genes around SH2B3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SH2B3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SH2B3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SH2B3 Gene

Proteins for SH2B3 Gene

  • Protein details for SH2B3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UQQ2-SH2B3_HUMAN
    Recommended name:
    SH2B adapter protein 3
    Protein Accession:
    Q9UQQ2
    Secondary Accessions:
    • B9EGG5
    • O95184

    Protein attributes for SH2B3 Gene

    Size:
    575 amino acids
    Molecular mass:
    63225 Da
    Quaternary structure:
    • Binds to the tyrosine-phosphorylated TCR zeta chain via its SH2 domain.

neXtProt entry for SH2B3 Gene

Post-translational modifications for SH2B3 Gene

No data available for DME Specific Peptides for SH2B3 Gene

Domains & Families for SH2B3 Gene

Gene Families for SH2B3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for SH2B3 Gene

GenScript: Design optimal peptide antigens:
  • SH2B3 protein (Q96BA5_HUMAN)
  • Signal transduction protein Lnk (SH2B3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UQQ2

UniProtKB/Swiss-Prot:

SH2B3_HUMAN :
  • Belongs to the SH2B adapter family.
Family:
  • Belongs to the SH2B adapter family.
genes like me logo Genes that share domains with SH2B3: view

Function for SH2B3 Gene

Molecular function for SH2B3 Gene

UniProtKB/Swiss-Prot Function:
Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.

Phenotypes From GWAS Catalog for SH2B3 Gene

Gene Ontology (GO) - Molecular Function for SH2B3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity IBA 21873635
GO:0005070 SH3/SH2 adaptor activity ISS,IEA --
GO:0005173 stem cell factor receptor binding ISS,IEA --
GO:0005515 protein binding IPI 16273093
GO:0035591 signaling adaptor activity IEA --
genes like me logo Genes that share ontologies with SH2B3: view
genes like me logo Genes that share phenotypes with SH2B3: view

Human Phenotype Ontology for SH2B3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SH2B3 Gene

MGI Knock Outs for SH2B3:

Animal Model Products

CRISPR Products

miRNA for SH2B3 Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SH2B3 Gene

Localization for SH2B3 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SH2B3 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 3
extracellular 1
mitochondrion 0
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SH2B3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IBA 21873635
genes like me logo Genes that share ontologies with SH2B3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for SH2B3 Gene

Pathways & Interactions for SH2B3 Gene

genes like me logo Genes that share pathways with SH2B3: view

SIGNOR curated interactions for SH2B3 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for SH2B3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001780 neutrophil homeostasis ISS 27430239
GO:0007165 signal transduction IEA --
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IEA --
GO:0007596 blood coagulation TAS --
GO:0008285 negative regulation of cell proliferation ISS,IEA --
genes like me logo Genes that share ontologies with SH2B3: view

Drugs & Compounds for SH2B3 Gene

(2) Drugs for SH2B3 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pazopanib Approved Pharma Target, inhibitor VEFGR, c-Kit, and PDGFR inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0

(2) Additional Compounds for SH2B3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SH2B3: view

Transcripts for SH2B3 Gene

mRNA/cDNA for SH2B3 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SH2B3 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11
SP1:
SP2:
SP3:
SP4:

Relevant External Links for SH2B3 Gene

GeneLoc Exon Structure for
SH2B3
ECgene alternative splicing isoforms for
SH2B3

Expression for SH2B3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SH2B3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SH2B3 Gene

This gene is overexpressed in Heart (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SH2B3 Gene



Protein tissue co-expression partners for SH2B3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SH2B3 Gene:

SH2B3

SOURCE GeneReport for Unigene cluster for SH2B3 Gene:

Hs.506784

mRNA Expression by UniProt/SwissProt for SH2B3 Gene:

Q9UQQ2-SH2B3_HUMAN
Tissue specificity: Preferentially expressed by lymphoid cell lines.

Evidence on tissue expression from TISSUES for SH2B3 Gene

  • Nervous system(4.3)
  • Bone marrow(2.5)
  • Blood(2.4)
  • Spleen(2.2)
  • Heart(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SH2B3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • nose
  • skull
Thorax:
  • bronchus
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • trachea
Abdomen:
  • liver
  • spleen
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with SH2B3: view

No data available for mRNA differential expression in normal tissues for SH2B3 Gene

Orthologs for SH2B3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SH2B3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SH2B3 33 32
  • 99.42 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SH2B3 33 32
  • 88.12 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SH2B3 33 32
  • 87.31 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Sh2b3 17 33 32
  • 79.97 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SH2B3 33
  • 65 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SH2B3 33
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves SH2B3 33 32
  • 68.23 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SH2B3 33
  • 46 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sh2b3 32
  • 58.85 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC101884640 32
  • 59.14 (n)
sh2b3 33
  • 36 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4732 32
fruit fly
(Drosophila melanogaster)
Insecta Lnk 33
  • 19 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 33 (a)
OneToMany
Species where no ortholog for SH2B3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SH2B3 Gene

ENSEMBL:
Gene Tree for SH2B3 (if available)
TreeFam:
Gene Tree for SH2B3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SH2B3: view image

Paralogs for SH2B3 Gene

Paralogs for SH2B3 Gene

genes like me logo Genes that share paralogs with SH2B3: view

Variants for SH2B3 Gene

Sequence variations from dbSNP and Humsavar for SH2B3 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs148636776 pathogenic, Familial erythrocytosis, 1, Essential thrombocythemia 111,447,491(+) G/A coding_sequence_variant, genic_downstream_transcript_variant, missense_variant, non_coding_transcript_variant
rs202080221 pathogenic, affects, Essential thrombocythemia, Familial erythrocytosis, 1 111,418,767(+) G/C/T coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant, stop_gained
rs587776885 pathogenic, Myelofibrosis 111,418,745(+) GCTGCGCT/GCT coding_sequence_variant, frameshift, genic_upstream_transcript_variant, non_coding_transcript_variant
rs72650673 uncertain-significance, not provided, Essential thrombocythemia, Familial erythrocytosis, 1, Myelofibrosis 111,447,506(+) G/A coding_sequence_variant, genic_downstream_transcript_variant, missense_variant, non_coding_transcript_variant
rs1555227037 uncertain-significance, not provided 111,447,015(+) CGGAGTGCACA/ coding_sequence_variant, downstream_transcript_variant, frameshift, genic_downstream_transcript_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for SH2B3 Gene

Variant ID Type Subtype PubMed ID
esv28093 CNV loss 19812545
nsv1071054 CNV deletion 25765185
nsv560170 CNV loss 21841781
nsv560171 CNV loss 21841781
nsv560172 CNV loss 21841781
nsv832513 CNV gain 17160897
nsv886 CNV deletion 18451855

Variation tolerance for SH2B3 Gene

Residual Variation Intolerance Score: 49.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.33; 76.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SH2B3 Gene

Human Gene Mutation Database (HGMD)
SH2B3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SH2B3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SH2B3 Gene

Disorders for SH2B3 Gene

MalaCards: The human disease database

(13) MalaCards diseases for SH2B3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
erythrocytosis, familial, 1
  • ecyt1
thrombocythemia 1
  • thcyt1
myelofibrosis
  • myelofibrosis with myeloid metaplasia, somatic
essential thrombocythemia
  • essential thrombocythaemia
growth retardation-mild developmental delay-chronic hepatitis syndrome
- elite association - COSMIC cancer census association via MalaCards
Search SH2B3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SH2B3_HUMAN
  • Celiac disease 13 (CELIAC13) [MIM:612011]: A multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. {ECO:0000269 PubMed:18311140}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:17554260}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for SH2B3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SH2B3: view

No data available for Genatlas for SH2B3 Gene

Publications for SH2B3 Gene

  1. Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation. (PMID: 10799879) Li Y … Hayashi J (Journal of immunology (Baltimore, Md. : 1950) 2000) 2 3 4 23 56
  2. Newly identified genetic risk variants for celiac disease related to the immune response. (PMID: 18311140) Hunt KA … van Heel DA (Nature genetics 2008) 3 4 43 56
  3. Novel associations for hypothyroidism include known autoimmune risk loci. (PMID: 22493691) Eriksson N … Do CB (PloS one 2012) 3 43 56
  4. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. (PMID: 21378990) Schunkert H … Samani NJ (Nature genetics 2011) 3 43 56
  5. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. (PMID: 21829393) Plagnol V … Todd JA (PLoS genetics 2011) 3 43 56

Products for SH2B3 Gene

Sources for SH2B3 Gene