SOCS6

protein-coding

suppressor of cytokine signaling 6, the group of Suppressors of cytokine signaling|SH2 domain containing

Gene summary

The protein encoded by this gene contains a SH2 domain and a CIS homolog domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by GM-CSF and EPO in hematopoietic cells. A high expression level of this gene was found in factor-independent chronic myelogenous leukemia (CML) and erythroleukemia (HEL) cell lines. [provided by RefSeq, Jul 2008]

Previous symbols:

SOCS4

MANE transcript

NM_004232.4

Inheritance

—

ClinVar variants

U:50B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr18:70,289,045-70,330,199

External References & Databases

Ensembl (ENSG00000170677)

Transcript & Mutation Effects

hg38 • Region Span ~41.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOCS6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004232.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			47 clinvar	4 clinvar		51
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	4	1	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004232.4	RefSeq	NP_004223.2	1	MANE Select
ENST00000397942.4	Ensembl	ENSP00000381034.3	1	MANE Select
ENST00000578377.1	Ensembl	ENSP00000463064.1	1	Standard
ENST00000582322.1	Ensembl	ENSP00000463395.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Prolactin signaling pathway - Homo sapiens (human)
Kit receptor signaling pathway
Signal Transduction
Post-translational protein modification

Biological Process

defense response
JAK-STAT cascade
negative regulation of signal transduction
proteasomal protein catabolic process
protein ubiquitination

Molecular Function

protein binding
1-phosphatidylinositol-3-kinase regulator activity

Cellular Component

immunological synapse
cytoplasm
cytosol
phosphatidylinositol 3-kinase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397942
Coding exons: 1
Length: 41300
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125744
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.854	283	326	0.867	0.0000203	3518
Missense (PolyPhen)		49	88.354	0.55459		999
Synonymous	-0.370	135	130	1.04	0.00000880	1071
Loss of Function	3.40	0	13.5	0.00	5.68e-7	190

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a 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 (By similarity). Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor. {ECO:0000250, ECO:0000269|PubMed:21030588}.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.0293
RVIS EVS: -1.02
RVIS percentile EVS: 7.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.675

Gene Damage Prediction

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