SOCS2 Gene (Protein Coding)

Suppressor Of Cytokine Signaling 2

GC12P093569
GIFtS:
43
This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal tra... See more...

Aliases for SOCS2 Gene

Aliases for SOCS2 Gene

  • Suppressor Of Cytokine Signaling 2 2 3 4 5
  • SOCS-2 2 3 4
  • STATI2 2 3 4
  • SSI-2 2 3 4
  • CIS2 2 3 4
  • SSI2 2 3 4
  • Cytokine-Inducible SH2 Protein 2 3 4
  • STAT-Induced STAT Inhibitor 2 3 4
  • Cish2 2 3
  • CIS-2 3 4
  • STAT-Induced STAT Inhibitor-2 2
  • SOCS2 5

External Ids for SOCS2 Gene

Previous GeneCards Identifiers for SOCS2 Gene

  • GC12P094485
  • GC12P093896
  • GC12P092466
  • GC12P093963
  • GC12P091030

Summaries for SOCS2 Gene

Entrez Gene Summary for SOCS2 Gene

  • This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal transduction, in part, by proteasomal depletion of receptors or signal-transducing proteins via ubiquitination. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10, interferon (IFN)-gamma and by cytokine receptors such as growth horomone receptor. The protein encoded by this gene interacts with the cytoplasmic domain of insulin-like growth factor-1 receptor (IGF1R) and is thought to be involved in the regulation of IGF1R mediated cell signaling. This gene has pseudogenes on chromosomes 20 and 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

GeneCards Summary for SOCS2 Gene

SOCS2 (Suppressor Of Cytokine Signaling 2) is a Protein Coding gene. Diseases associated with SOCS2 include Primary Polycythemia and Placental Insufficiency. Among its related pathways are Relaxin signaling pathway and IL-2 Pathway. Gene Ontology (GO) annotations related to this gene include SH3/SH2 adaptor activity and insulin-like growth factor receptor binding. An important paralog of this gene is CISH.

UniProtKB/Swiss-Prot Summary for SOCS2 Gene

  • SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Gene Wiki entry for SOCS2 Gene

Additional gene information for SOCS2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SOCS2 Gene

Genomics for SOCS2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for SOCS2 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 SOCS2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SOCS2

Top Transcription factor binding sites by QIAGEN in the SOCS2 gene promoter:
  • GATA-1
  • ITF-2
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT5B
  • Tal-1beta

Genomic Locations for SOCS2 Gene

Genomic Locations for SOCS2 Gene
chr12:93,569,814-93,626,236
(GRCh38/hg38)
Size:
56,423 bases
Orientation:
Plus strand
chr12:93,963,590-93,977,263
(GRCh37/hg19)
Size:
13,674 bases
Orientation:
Plus strand

Genomic View for SOCS2 Gene

Genes around SOCS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SOCS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SOCS2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for SOCS2 Gene

Proteins for SOCS2 Gene

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  • Protein details for SOCS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14508-SOCS2_HUMAN
    Recommended name:
    Suppressor of cytokine signaling 2
    Protein Accession:
    O14508
    Secondary Accessions:
    • A8K3D1
    • O14542
    • O95102
    • Q9UKS5

    Protein attributes for SOCS2 Gene

    Size:
    198 amino acids
    Molecular mass:
    22172 Da
    Quaternary structure:
    • Interacts with IGF1R (PubMed:9727029). Associates with the Elongin BC complex (PubMed:16675548). Interacts with AREL1 (PubMed:31578312). Interacts with PRKCA (By similarity).

    Three dimensional structures from OCA and Proteopedia for SOCS2 Gene

neXtProt entry for SOCS2 Gene

Protein Expression for SOCS2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for SOCS2 Gene

  • Ubiquitinated; mediated by AREL1 and leading to its subsequent proteasomal degradation (PubMed:31578312). Ubiquitination is dependent on its phosphorylation at Ser-52, by PKC (PubMed:31578312). Ubiquitination is stimulated by LPS (By similarity).
  • Phosphorylation at Ser-52 by PKC facilitates its ubiquitination and proteosomal degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SOCS2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SOCS2 Gene

Domains & Families for SOCS2 Gene

Gene Families for SOCS2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for SOCS2 Gene

InterPro:
Blocks:
  • SH2 domain signature
  • SOCS protein, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for SOCS2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ93661, Homo sapiens suppressor of cytokine signaling 2 (SOCS2), mRNA (A8K3D1_HUMAN)
  • cDNA FLJ52461, highly similar to Suppressor of cytokine signaling 2 (B4DMW5_HUMAN)
  • Suppressor of cytokine signaling-2 (B5BU82_HUMAN)
  • STAT-induced STAT inhibitor 2 (SOCS2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14508

UniProtKB/Swiss-Prot:

SOCS2_HUMAN :
  • The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
Domain:
  • The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
genes like me logo Genes that share domains with SOCS2: view

Function for SOCS2 Gene

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Molecular function for SOCS2 Gene

UniProtKB/Swiss-Prot Function:
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
UniProtKB/Swiss-Prot Induction:
By a subset of cytokines, including EPO/erythropoietin and CSF2/GM-CSF.
GENATLAS Biochemistry:
suppressor of cytokine signaling 2. Involved in the interleukin-6 induced receptor phosphorylation and in the negative regulation of cytokine induced STAT factor signaling,putative candidate for asthma and atopy susceptibility

Phenotypes From GWAS Catalog for SOCS2 Gene

Gene Ontology (GO) - Molecular Function for SOCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005070 SH3/SH2 adaptor activity TAS --
GO:0005131 growth hormone receptor binding NAS 12135564
GO:0005159 insulin-like growth factor receptor binding IPI 9727029
GO:0005515 protein binding IPI 11781573
GO:0008269 JAK pathway signal transduction adaptor activity TAS,IEA --
genes like me logo Genes that share ontologies with SOCS2: view
genes like me logo Genes that share phenotypes with SOCS2: view

Animal Models for SOCS2 Gene

MGI Knock Outs for SOCS2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOCS2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SOCS2 Gene

Localization for SOCS2 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 SOCS2 gene
Compartment Confidence
cytosol 5
extracellular 3
nucleus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SOCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm NAS 9727029
GO:0005829 cytosol TAS --
GO:0005942 phosphatidylinositol 3-kinase complex IBA 21873635
genes like me logo Genes that share ontologies with SOCS2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for SOCS2 Gene

Pathways & Interactions for SOCS2 Gene

PathCards logo

SuperPathways for SOCS2 Gene

SuperPathway Contained pathways
1 Prolactin Signaling Pathway
Prolactin Signaling Pathway
.38
Prolactin signaling pathway
.34
Leptin signaling pathway
.33
2 IL-2 Pathway
Prolactin Signaling
.54
Growth Hormone Signaling
.49
IL-4 Pathway
.34
3 PEDF Induced Signaling
IL-6 Pathway
.61
STAT3 Pathway
.47
4 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
Immune response IL-9 signaling pathway
.42
IL-9 Pathway
.36
5 TGF-Beta Pathway
JAK-STAT Pathway
.57
SOCS Pathway
.41
genes like me logo Genes that share pathways with SOCS2: view

Pathways by source for SOCS2 Gene

2 Sino Biological pathways for SOCS2 Gene
2 GeneGo (Thomson Reuters) pathways for SOCS2 Gene
  • Immune response IL-9 signaling pathway
  • Inhibitory action of Lipoxin A4 on PDGF, EGF and LTD4 signaling
8 Qiagen pathways for SOCS2 Gene
  • Growth Hormone Signaling
  • IL-4 Pathway
  • IL-6 Pathway
  • IL-9 Pathway
  • JAK-STAT Pathway
1 Cell Signaling Technology pathway for SOCS2 Gene
1 GeneTex pathway for SOCS2 Gene

UniProtKB/Swiss-Prot O14508-SOCS2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for SOCS2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for SOCS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth NAS 9727029
GO:0007259 JAK-STAT cascade TAS 9266833
GO:0007595 lactation IEA --
GO:0009966 regulation of signal transduction NAS 9727029
GO:0009967 positive regulation of signal transduction IEA --
genes like me logo Genes that share ontologies with SOCS2: view

Drugs & Compounds for SOCS2 Gene

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  1. Drug

(3) Drugs for SOCS2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for SOCS2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SOCS2: view

Transcripts for SOCS2 Gene

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  1. CRISPR
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  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for SOCS2 Gene

6 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SOCS2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SOCS2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b · 8c · 8d · 8e ^ 9a · 9b ^ 10
SP1: - - - - - - - - -
SP2: - - - - - - - -
SP3: - - - - - - -
SP4: - - - - - -
SP5: - - - -
SP6: - - -
SP7: - -
SP8: -
SP9: -
SP10:

Relevant External Links for SOCS2 Gene

GeneLoc Exon Structure for
SOCS2

Expression for SOCS2 Gene

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  1. Primer
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SOCS2 Gene

mRNA expression in normal human tissues for SOCS2 Gene
mRNA expression by GTEx for SOCS2 GenemRNA expression by BioGPS for SOCS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SOCS2 Gene

This gene is overexpressed in Bone (49.8), Liver (9.5), and Heart (9.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SOCS2 Gene



Protein tissue co-expression partners for SOCS2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SOCS2

SOURCE GeneReport for Unigene cluster for SOCS2 Gene:

Hs.485572

mRNA Expression by UniProt/SwissProt for SOCS2 Gene:

O14508-SOCS2_HUMAN
Tissue specificity: High expression in heart, placenta, lung, kidney and prostate. Predominantly expressed in pulmonary epithelia cells, specifically type II pneumocytes.

Evidence on tissue expression from TISSUES for SOCS2 Gene

  • Nervous system(4.8)
  • Lung(4.6)
  • Liver(3.5)
  • Eye(3.1)
  • Muscle(3)
  • Heart(3)
  • Stomach(2.8)
  • Kidney(2.7)
  • Intestine(2.7)
  • Blood(2.5)
  • Lymph node(2.5)
  • Spleen(2.5)
  • Bone marrow(2.4)
  • Adrenal gland(2.3)
  • Pancreas(2.2)
  • Skin(2.1)
  • Thyroid gland(2.1)
genes like me logo Genes that share expression patterns with SOCS2: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SOCS2 Gene

Orthologs for SOCS2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SOCS2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia SOCS2 30 31
  • 99.83 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia SOCS2 30 31
  • 95.45 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia SOCS2 30 31
  • 94.44 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Gm9847 31
  • 93 (a)
 OneToMany
Socs2 30 17 31
  • 90.91 (n)
 OneToMany
Rat
(Rattus norvegicus)
 Mammalia Socs2 30
  • 89.39 (n)
Platypus
(Ornithorhynchus anatinus)
 Mammalia SOCS2 31
  • 82 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia SOCS2 31
  • 81 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves SOCS2 30 31
  • 72.71 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia SOCS2 31
  • 69 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia socs2 30
  • 67.17 (n)
Str.4310 30
Zebrafish
(Danio rerio)
 Actinopterygii socs2 30 31
  • 57.89 (n)
 OneToOne
Species where no ortholog for SOCS2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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 SOCS2 Gene

ENSEMBL:
Gene Tree for SOCS2 (if available)
TreeFam:
Gene Tree for SOCS2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SOCS2: view image

Paralogs for SOCS2 Gene

Paralogs for SOCS2 Gene

(4) SIMAP similar genes for SOCS2 Gene using alignment to 7 proteins:

  • SOCS2_HUMAN
  • B5BU82_HUMAN
  • F8VRV3_HUMAN
  • F8VS53_HUMAN
  • F8VU91_HUMAN
  • S4R3W1_HUMAN
  • S4R3Z4_HUMAN

Pseudogenes.org Pseudogenes for SOCS2 Gene

genes like me logo Genes that share paralogs with SOCS2: view

Variants for SOCS2 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SOCS2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs3741676 - p.Ser52Asn

Additional dbSNP identifiers (rs#s) for SOCS2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SOCS2 Gene

Variant ID Type Subtype PubMed ID
dgv2791n54 CNV loss 21841781
dgv2792n54 CNV gain 21841781
esv25615 CNV loss 19812545
nsv559778 CNV gain 21841781
nsv7234 OTHER inversion 18451855

Variation tolerance for SOCS2 Gene

Residual Variation Intolerance Score: 43.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.59; 56.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SOCS2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SOCS2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SOCS2 Gene

Disorders for SOCS2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SOCS2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
primary polycythemia
  • polycythemia vera
placental insufficiency
  • uteroplacental vascular insufficiency
myeloproliferative neoplasm
  • campomelic dysplasia
essential thrombocythemia
  • essential thrombocythaemia
glycine n-methyltransferase deficiency
  • gnmt deficiency
- elite association - COSMIC cancer census association via MalaCards
Search SOCS2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SOCS2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with SOCS2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SOCS2 Gene

Publications for SOCS2 Gene

  1. Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. (PMID: 9266833) Minamoto S … Kishimoto T (Biochemical and biophysical research communications 1997) 2 3 4 23
  2. Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese. (PMID: 16406727) Kato H … Itakura M (Genomics 2006) 3 23 41
  3. Cloning and characterization of novel CIS family genes. (PMID: 9344848) Masuhara M … Yoshimura A (Biochemical and biophysical research communications 1997) 2 3 4
  4. KIAA0317 regulates pulmonary inflammation through SOCS2 degradation. (PMID: 31578312) Lear TB … Chen BB (JCI insight 2019) 3 4
  5. Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls. (PMID: 20503287) Schuurhof A … Janssen R (Pediatric pulmonology 2010) 3 41

ExternalLinks

View latest publications for SOCS2 gene in Mastermind

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