SOCS5
protein-codingsuppressor of cytokine signaling 5, 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) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The specific function of this protein has not yet been determined. Two alternatively spliced transcript variants encoding an identical protein have been reported. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~81.3 kbGenCC 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 SOCS5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144949.3. 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 | 3 | 4 | |||
| missense | 76 | 3 | 79 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 77 | 3 | 3 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_659198.1 | 1 | MANE Select | |
| Ensembl | ENSP00000378330.2 | 1 | MANE Select | |
| RefSeq | NP_054730.1 | 1 | Standard | |
| Ensembl | ENSP00000305133.5 | 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)
- IL-4 Signaling Pathway
- HDAC6 interactions
- Interleukin-4 and 13 signaling
Biological Process
- epidermal growth factor receptor signaling pathway
- negative regulation of epidermal growth factor-activated receptor activity
- JAK-STAT cascade
- negative regulation of signal transduction
- protein ubiquitination
Molecular Function
- epidermal growth factor receptor binding
- protein binding
- receptor tyrosine kinase binding
- 1-phosphatidylinositol-3-kinase regulator activity
Cellular Component
- cytosol
- phosphatidylinositol 3-kinase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306503
- Coding exons
- 1
- Length
- 64178
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125742
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.690 | 269 | 303 | 0.888 | 0.0000167 | 3545 |
| Missense (PolyPhen) | 84 | 124.81 | 0.67303 | 1542 | ||
| Synonymous | -1.36 | 128 | 110 | 1.17 | 0.00000624 | 1016 |
| Loss of Function | 3.27 | 4 | 19.6 | 0.204 | 0.00000115 | 230 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- 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. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T-helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes differentiation into the Th2 phenotype. Can also partially inhibit IL6 and LIF signaling. {ECO:0000269|PubMed:15590694}.;
Recessive Scores
- pRec
- 0.232
Intolerance Scores
- LoFtool
- 0.472
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.945
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |