SOCS4

protein-coding

suppressor of cytokine signaling 4, the group of Suppressors of cytokine signaling|SH2 domain containing

Gene summary

The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS), also known as STAT-induced STAT inhibitor (SSI), protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

SOCS7

MANE transcript

NM_199421.2

Inheritance

ClinVar variants

U:57B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr14:55,027,230-55,049,489

External References & Databases

Ensembl (ENSG00000180008)

Transcript & Mutation Effects

hg38 • Region Span ~22.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autoimmune diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007179

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOCS4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199421.2. 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			1 clinvar		2 clinvar	3
missense			56 clinvar	1 clinvar		57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	57	1	2	60

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199421.2	RefSeq	NP_955453.1	1	MANE Select
ENST00000555846.2	Ensembl	ENSP00000452522.1	1	MANE Select
NM_080867.3	RefSeq	NP_543143.1	1	Standard
ENST00000339298.2	Ensembl	ENSP00000341327.2	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Type II diabetes mellitus - Homo sapiens (human)
Jak-STAT signaling pathway - Homo sapiens (human)
Prolactin signaling pathway - Homo sapiens (human)
Insulin signaling pathway - Homo sapiens (human)
Type II diabetes mellitus

Biological Process

negative regulation of epidermal growth factor-activated receptor activity
protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
intracellular signal transduction
regulation of growth

Molecular Function

protein binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395472
Coding exons: 1
Length: 22259
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125744
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.637	208	236	0.883	0.0000125	2930
Missense (PolyPhen)		78	97.771	0.79779		1225
Synonymous	0.285	83	86.4	0.961	0.00000479	815
Loss of Function	1.43	10	16.2	0.617	0.00000119	182

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000065	0.000065	rare
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. 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. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR. {ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:17997974}.;

Recessive Scores

pRec: 0.160

Intolerance Scores

LoFtool: 0.780
RVIS EVS: -0.42
RVIS percentile EVS: 25.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.922

Gene Damage Prediction

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