SOCS3
suppressor of cytokine signaling 3, the group of SH2 domain containing|Suppressors of cytokine signaling
Basic information
Region (hg38): 17:78356777-78360077
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (7 variants)
- not specified (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOCS3 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 7 | 0 | 1 |
Variants in SOCS3
This is a list of pathogenic ClinVar variants found in the SOCS3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-78358464-G-A | not specified | Uncertain significance (Mar 11, 2024) | ||
| 17-78358474-T-A | not specified | Uncertain significance (May 15, 2023) | ||
| 17-78358485-T-C | not specified | Uncertain significance (Jun 26, 2023) | ||
| 17-78358654-G-A | not specified | Uncertain significance (Nov 09, 2023) | ||
| 17-78358665-G-A | not specified | Uncertain significance (May 03, 2023) | ||
| 17-78358675-T-C | not specified | Uncertain significance (Jan 31, 2023) | ||
| 17-78358688-G-T | not specified | Benign (May 04, 2022) | ||
| 17-78358968-T-C | not specified | Uncertain significance (Oct 03, 2022) | ||
| 17-78358971-T-C | not specified | Uncertain significance (Oct 06, 2021) | ||
| 17-78359019-C-T | not specified | Uncertain significance (Nov 05, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SOCS3 | protein_coding | protein_coding | ENST00000330871 | 1 | 3295 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.746 | 0.244 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.86 | 78 | 140 | 0.557 | 0.00000797 | 1437 |
| Missense in Polyphen | 16 | 49.485 | 0.32333 | 512 | ||
| Synonymous | -0.939 | 76 | 66.3 | 1.15 | 0.00000407 | 483 |
| Loss of Function | 1.97 | 0 | 4.53 | 0.00 | 1.92e-7 | 55 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo (By similarity). 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. Seems to recognize IL6ST (By similarity). {ECO:0000250, ECO:0000269|PubMed:15601820}.;
- Disease
- DISEASE: Note=There is some evidence that SOCS3 may be a susceptibility gene for atopic dermatitis linked to 17q25. SOCS3 messenger RNA is significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls. Furthermore, a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene has been found in two independent groups of patients. {ECO:0000269|PubMed:16685656}.;
- Pathway
- Adipocytokine signaling pathway - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Ncore;Leptin signaling pathway;Prolactin Signaling Pathway;Interleukin-11 Signaling Pathway;Adipogenesis;Oncostatin M Signaling Pathway;JAK-STAT;Mammary gland development pathway - Involution (Stage 4 of 4);Apoptosis-related network due to altered Notch3 in ovarian cancer;IL-6 signaling pathway;Signaling by PTK6;IL-4 Signaling Pathway;Leptin Insulin Overlap;Interleukin-4 and 13 signaling;Transcriptional regulation by RUNX1;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Insulin Signaling;IL-2 Signaling Pathway;Interferon type I signaling pathways;Type II interferon signaling (IFNG);Signaling by PTK6;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;Growth hormone receptor signaling;il-2 receptor beta chain in t cell activation;il22 soluble receptor signaling pathway;Generic Transcription Pathway;Prolactin;Cytokine Signaling in Immune system;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Growth hormone signaling;Regulation of IFNG signaling;Oncostatin_M;Immune System;Adaptive Immune System;ATF-2 transcription factor network;Antigen processing: Ubiquitination & Proteasome degradation;PTK6 Activates STAT3;Class I MHC mediated antigen processing & presentation;EGFR1;Neddylation;JAK STAT pathway and regulation;IL2;Signaling by Leptin;Signaling by Non-Receptor Tyrosine Kinases;IL3;IL2-mediated signaling events;Interferon gamma signaling;EPO signaling pathway;Leptin;IL6;Regulation of IFNA signaling;Interferon alpha/beta signaling;RUNX1 regulates transcription of genes involved in differentiation of keratinocytes;IL23-mediated signaling events;Transcriptional regulation by RUNX1;Interferon Signaling;IL4-mediated signaling events;Signaling events mediated by PTP1B;Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.655
Intolerance Scores
- loftool
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.04
Haploinsufficiency Scores
- pHI
- 0.823
- hipred
- Y
- hipred_score
- 0.672
- ghis
- 0.592
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Socs3
- Phenotype
- skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- socs3a
- Affected structure
- posterior lateral line neuromast
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of protein kinase activity;JAK-STAT cascade;protein ubiquitination;cytokine-mediated signaling pathway;regulation of growth;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of tyrosine phosphorylation of STAT protein;negative regulation of apoptotic process;regulation of phosphatidylinositol 3-kinase activity;post-translational protein modification;positive regulation of cell differentiation;negative regulation of JAK-STAT cascade;negative regulation of insulin receptor signaling pathway;phosphatidylinositol phosphorylation;negative regulation of inflammatory response;regulation of interferon-gamma-mediated signaling pathway;branching involved in labyrinthine layer morphogenesis;placenta blood vessel development;trophoblast giant cell differentiation;spongiotrophoblast differentiation;interleukin-6-mediated signaling pathway;cellular response to leukemia inhibitory factor
- Cellular component
- cytosol;phosphatidylinositol 3-kinase complex
- Molecular function
- phosphotyrosine residue binding;protein kinase inhibitor activity;protein binding;1-phosphatidylinositol-3-kinase regulator activity