SOCS1

suppressor of cytokine signaling 1, the group of SH2 domain containing|Suppressors of cytokine signaling

Basic information

Region (hg38): 16:11254417-11256204

Links

ENSG00000185338 ∙ ∙ OMIM:603597 ∙ HGNC:19383 ∙ Uniprot:O15524 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoimmune disease (Limited), mode of inheritance: AD
• autoinflammatory syndrome with immunodeficiency (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammatory syndrome, familial, with or without immunodeficiency	AD	Allergy/Immunology/Infectious	The condition has been described as involving recurrent infections and autoimmune disorder, and medical management (eg, with steroids, rituximab) has been described as beneficial	Allergy/Immunology/Infectious; Hematologic	32499645; 32853638; 33087723

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOCS1 gene.

• not provided (2 variants)
• Autoimmune hemolytic anemia;Autoimmune thrombocytopenia (2 variants)
• Autoinflammatory syndrome with immunodeficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOCS1 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				3	2	5
missense			32	1		33
nonsense		3				3
start loss			1			1
frameshift	2		1			3
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	2	3	36	4	4

Variants in SOCS1

This is a list of pathogenic ClinVar variants found in the SOCS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-11254849-C-G		not specified	Likely benign (Mar 01, 2023)
16-11254862-G-A		not specified	Uncertain significance (Mar 20, 2024)
16-11254875-C-T		Autoinflammatory syndrome with immunodeficiency	Uncertain significance (Dec 02, 2024)
16-11254880-A-G		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
16-11254882-G-A			Benign (Sep 01, 2022)
16-11254902-G-A			Uncertain significance (Feb 10, 2022)
16-11254909-G-C		not specified	Uncertain significance (Apr 28, 2022)
16-11254915-G-A			Benign (Aug 10, 2018)
16-11254919-C-T		Autoinflammatory syndrome with immunodeficiency	Likely pathogenic (Oct 04, 2023)
16-11254961-G-A		not specified	Uncertain significance (Jun 27, 2022)
16-11254968-C-T		not specified	Uncertain significance (Jun 28, 2022)
16-11254991-C-G		not specified	Uncertain significance (Feb 28, 2023)
16-11254997-A-G		not specified	Uncertain significance (Jun 07, 2024)
16-11254998-T-TGCCGC		Autoinflammatory syndrome with immunodeficiency	Pathogenic (Jun 17, 2021)
16-11254998-T-TGCGGC		Autoimmune hemolytic anemia;Autoimmune thrombocytopenia • Autoinflammatory syndrome with immunodeficiency	Pathogenic (Jul 01, 2021)
16-11255013-C-A		not specified	Uncertain significance (Feb 17, 2024)
16-11255016-C-G		not specified	Uncertain significance (Dec 28, 2023)
16-11255016-C-T			Uncertain significance (Jul 19, 2022)
16-11255017-G-T		Malignant lymphoma, large B-cell, diffuse • Neoplasm	Pathogenic (Dec 04, 2023)
16-11255019-A-G		Systemic lupus erythematosus • AUTOINFLAMMATORY SYNDROME, FAMILIAL, WITHOUT IMMUNODEFICIENCY	Pathogenic/Likely pathogenic (Jun 17, 2021)
16-11255025-C-A		Autoinflammatory syndrome with immunodeficiency	Likely pathogenic (Apr 04, 2024)
16-11255040-G-A		not specified	Uncertain significance (Jan 10, 2023)
16-11255046-C-G			Uncertain significance (Jan 01, 2023)
16-11255055-C-G		not specified	Uncertain significance (Feb 15, 2022)
16-11255058-G-C		not specified	Uncertain significance (Sep 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOCS1	protein_coding	protein_coding	ENST00000332029	1	1775

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.585	0.376	117046	0	1	117047	0.00000427

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.829	67	89.0	0.753	0.00000417	1285
Missense in Polyphen		8	28.827	0.27752		404
Synonymous	-3.09	66	40.9	1.61	0.00000190	464
Loss of Function	1.53	0	2.73	0.00	1.19e-7	34

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000104	0.000104
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: dbNSFP

• Function: FUNCTION: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein- tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival (By similarity). Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2. SOCS1 appears to be a negative regulator in IGF1R signaling pathway. {ECO:0000250|UniProtKB:O35716, ECO:0000269|PubMed:11278610, ECO:0000269|PubMed:11313480}.
• Pathway: Type II diabetes mellitus - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);JAK-STAT-Ncore;Regulation of toll-like receptor signaling pathway;Prolactin Signaling Pathway;Adipogenesis;Kit receptor signaling pathway;IL-4 Signaling Pathway;Leptin Insulin Overlap;Interleukin-4 and 13 signaling;The human immune response to tuberculosis;Insulin Signaling;EPO Receptor Signaling;Interferon type I signaling pathways;Type II interferon signaling (IFNG);Interleukin-4 and 13 signaling;Signal Transduction;Signaling by Interleukins;Growth hormone receptor signaling;il-2 receptor beta chain in t cell activation;Prolactin;Cytokine Signaling in Immune system;Toll-Like Receptors Cascades;Growth hormone signaling;Regulation of IFNG signaling;Innate Immune System;Immune System;Adaptive Immune System;KitReceptor;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Regulation of KIT signaling;EGFR1;JAK STAT pathway and regulation;IL2-mediated signaling events;Interferon gamma signaling;IFN-gamma pathway;IL4;Signaling by SCF-KIT;IL5;Toll Like Receptor 4 (TLR4) Cascade;Regulation of IFNA signaling;Interferon alpha/beta signaling;Signaling by Receptor Tyrosine Kinases;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Interferon Signaling;Signaling events mediated by Stem cell factor receptor (c-Kit);IL4-mediated signaling events;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.544

Haploinsufficiency Scores

• pHI: 0.171
• hipred: Y
• hipred_score: 0.767
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Socs1
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; endocrine/exocrine gland 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); growth/size/body region phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; neoplasm; normal phenotype; 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); reproductive system 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); liver/biliary system phenotype; respiratory system phenotype

Zebrafish Information Network

• Gene name: socs1a
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: regulation of protein phosphorylation;negative regulation of protein kinase activity;JAK-STAT cascade;regulation of activation of Janus kinase activity;protein ubiquitination;cytokine-mediated signaling pathway;interleukin-7-mediated signaling pathway;regulation of growth;negative regulation of tyrosine phosphorylation of STAT protein;positive regulation of CD4-positive, alpha-beta T cell differentiation;negative regulation of CD8-positive, alpha-beta T cell differentiation;regulation of phosphatidylinositol 3-kinase activity;fat cell differentiation;positive regulation of regulatory T cell differentiation;negative regulation of JAK-STAT cascade;negative regulation of insulin receptor signaling pathway;phosphatidylinositol phosphorylation;regulation of cytokine secretion;regulation of interferon-gamma-mediated signaling pathway;cellular response to amino acid stimulus
• Cellular component: nucleoplasm;cytoplasm;cytosol;phosphatidylinositol 3-kinase complex;cytoplasmic vesicle;cytoplasmic ribonucleoprotein granule
• Molecular function: protein kinase inhibitor activity;insulin-like growth factor receptor binding;protein binding;kinase inhibitor activity;protein kinase binding;1-phosphatidylinositol-3-kinase regulator activity