SOCS5

Summary

SOCS5 (suppressor of cytokine signaling 5, HGNC:16852) is a protein-coding gene on chromosome 2p21, encoding Suppressor of cytokine signaling 5 (O75159). SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction.

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.

Source: NCBI Gene 9655 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_144949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16852
Approved symbol	SOCS5
Name	suppressor of cytokine signaling 5
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0671, SOCS-5, CIS6, CISH6, Cish5
Ensembl gene	ENSG00000171150
Ensembl biotype	protein_coding
OMIM	607094
Entrez	9655

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000306503, ENST00000394861, ENST00000568862, ENST00000650009, ENST00000861862, ENST00000861863, ENST00000861864, ENST00000861865, ENST00000929596, ENST00000929597, ENST00000952072, ENST00000952073

RefSeq mRNA: 2 — MANE Select: NM_144949 NM_014011, NM_144949

CCDS: CCDS1830

Canonical transcript exons

ENST00000394861 — 2 exons

Exon	Start	End
ENSE00001519828	46699295	46699449
ENSE00001874549	46758519	46763129

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.51.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5891 / max 24.7785, expressed in 779 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20105	3.6084	1277
20104	1.5891	779
20106	0.9514	466

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.51	gold quality
buccal mucosa cell	CL:0002336	93.90	gold quality
endothelial cell	CL:0000115	93.72	gold quality
male germ cell	CL:0000015	93.64	gold quality
germinal epithelium of ovary	UBERON:0001304	93.03	gold quality
mammary duct	UBERON:0001765	92.77	gold quality
parietal pleura	UBERON:0002400	92.69	gold quality
saphenous vein	UBERON:0007318	92.37	gold quality
cerebellar vermis	UBERON:0004720	92.23	gold quality
epithelium of mammary gland	UBERON:0003244	92.05	gold quality
stromal cell of endometrium	CL:0002255	91.69	gold quality
choroid plexus epithelium	UBERON:0003911	91.67	gold quality
vena cava	UBERON:0004087	91.44	gold quality
pleura	UBERON:0000977	91.32	gold quality
seminal vesicle	UBERON:0000998	90.65	gold quality
decidua	UBERON:0002450	90.23	gold quality
visceral pleura	UBERON:0002401	90.06	gold quality
biceps brachii	UBERON:0001507	89.59	gold quality
calcaneal tendon	UBERON:0003701	89.43	gold quality
pericardium	UBERON:0002407	89.42	gold quality
mammary gland	UBERON:0001911	89.20	gold quality
thoracic mammary gland	UBERON:0005200	89.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.11	gold quality
urethra	UBERON:0000057	89.06	gold quality
hair follicle	UBERON:0002073	89.06	gold quality
cartilage tissue	UBERON:0002418	88.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.60	gold quality
cauda epididymis	UBERON:0004360	88.44	gold quality
cranial nerve II	UBERON:0000941	88.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.01	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.27
E-MTAB-7052	no	334.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LDLR, STAT1, STAT3, TFCP2

miRNA regulators (miRDB)

243 targeting SOCS5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 30)

• The reduction in EGFR levels and EGF-induced signaling in SOCS5-expressing cells requires both the Src homology-2 and SOCS box domains of SOCS5. (PMID:15590694)
• Constitutive expression of SOCS5 in transgenic mice results in reduced eosinophil infiltration in allergic conjunctivitis (PMID:16210657)
• Up regulation of SOCS1 and SOCS5 expression and down-regulation of SOCS3 and CIS may correlate with the development of a Th1 mediated immune response in Vogt-Koyanagi-Harada disease. (PMID:20137421)
• The results may contribute to understanding SOCS5 and SOCS6 expression regulation in various cancer tissues, and show that these two factors may be used for diagnosing cancer. (PMID:22081311)
• Identified is a conserved region of about 70 residues in the N-terminal domains of SOCS4 and 5 that is predicted to be more ordered than the surrounding sequence. (PMID:22423360)
• Exogenous miR-9 effectively reduced SOCS5 levels, leading to activated JAK-STAT pathway, which promoted endothelial cell migration and tumour angiogenesis (PMID:22773185)
• different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling with JAK1 and SHC-1 (PMID:23990909)
• The rs6737848 SOCS5 polymorphism was significantly associated with asthma in additive model and in dominant model (PMID:24340963)
• Opisthorchis felineus infection diminishes the risk of atopic bronchial asthma associated with the SOCS5 gene polymorphism. (PMID:25017311)
• These findings indicate that SOCS5 mediates the impaired function of dendritic cells in chronic lymphocytic leukemia patients (PMID:27317770)
• Here the authors show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). (PMID:28195529)
• This study showed that SOCS5 expression was significantly down-regulated. (PMID:28196747)
• Data show that the Japanese encephalitis virus (JEV)-induced expression of miR-301a led to inhibition of the production of the transcription factor IFN regulatory factor 1 (IRF1) and the signaling protein suppressor of cytokine signaling 5 (SOCS5). (PMID:28196914)
• We validated SOCS5 as a bona fide target of mir-18 and mir-25, and established, for the first time, the tumor suppressive role of SOCS5 in liver cancer (PMID:30191950)
• our data implicated that miR-132 may promote inflammation…via targeting SOCS5 in chronic obstructive pulmonary disease (PMID:30292646)
• Data show that suppressor of cytokine signaling 5 (SOCS5) was differentially expressed in primary T-cell leukemia, acute (T-ALL). (PMID:30974024)
• Homozygous genotype of capital ES, Cyrilliccapital ES, Cyrillic gene of SOCS5 is a risk factor for allergic bronchial asthma (PMID:31094455)
• Mechanistic investigations demonstrated that TUSC7 can interact with miR-616 and decrease its expression, thereby upregulating the expression of miR-616’s targets SOCS4 (SOCS5). (PMID:31200002)
• MicroRNA-301a promotes pancreatic cancer invasion and metastasis through the JAK/STAT3 signaling pathway by targeting SOCS5. (PMID:31233116)
• This study revealed a novel metastasis-promoting function of SOCS5 in hepatocellular carcinoma. (PMID:31406106)
• data indicated thatthe overexpression of FER1L4 promoted apoptosis and inhibited the EMT markers expression and PI3K/AKT signaling pathway activation in OS cells via downregulating miR-18a-5p to promote SOCS5. (PMID:31473323)
• MiR-9-5p could promote angiogenesis and radiosensitivity in cervical cancer by targeting SOCS5. (PMID:31539118)
• lncRNA HAND2-AS1 Inhibits Liver Cancer Cell Proliferation and Migration by Upregulating SOCS5 to Inactivate the JAK-STAT Pathway. (PMID:32155348)
• Long non-coding RNA HCG11 sponging miR-522-3p inhibits the tumorigenesis of non-small cell lung cancer by upregulating SOCS5. (PMID:32844573)
• LncRNA CASC2 inhibits cell proliferation, metastasis and EMT through miR-18a/SOCS5 axis in cholangiocarcinoma. (PMID:32894543)
• LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis. (PMID:34666613)
• Inhibition of microRNA-448 suppresses CD4(+) T cell inflammatory activation via up-regulating suppressor of cytokine signaling 5 in systemic lupus erythematosus. (PMID:35121374)
• Resistin stimulates PC-3 prostate cancer cell growth through stimulation of SOCS3 and SOCS5 genes. (PMID:37646261)
• Evaluation of SOCS5 mRNA and its association with serum IL-12 levels and rs41379147 SNP in various subsets of allergic disorders: A case control study. (PMID:37672963)
• Sequential inspiratory muscle exercise-noninvasive positive pressure ventilation alleviates oxidative stress in COPD by mediating SOCS5/JAK2/STAT3 pathway. (PMID:37828534)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	socs1b	ENSDARG00000089873
mus_musculus	Socs5	ENSMUSG00000037104
rattus_norvegicus	Socs5	ENSRNOG00000028504
drosophila_melanogaster	Socs44A	FBGN0033266
drosophila_melanogaster	Socs36E	FBGN0041184

Paralogs (7): CISH (ENSG00000114737), SOCS2 (ENSG00000120833), SOCS6 (ENSG00000170677), SOCS4 (ENSG00000180008), SOCS3 (ENSG00000184557), SOCS1 (ENSG00000185338), SOCS7 (ENSG00000274211)

Protein

Protein identifiers

Suppressor of cytokine signaling 5 — O75159 (reviewed: O75159)

Alternative names: Cytokine-inducible SH2 protein 6, Cytokine-inducible SH2-containing protein 5

All UniProt accessions (2): A0A3B3ISP4, O75159

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with IL4R; inhibits IL4 signaling. Interacts with EGFR. Interacts with ELOB and ELOC; mediates EGFR ubiquitination and degradation.

Post-translational modifications. Phosphorylated. Phosphorylation is induced by EGF.

Domain organisation. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

Induction. Up-regulated by EGF (at protein level).

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_054730, NP_659198* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001496	SOCS_box	Domain
IPR022252	SOCS4/SOCS5_dom	Domain
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037343	SOCS5_SOCS	Domain

Pfam: PF00017, PF07525, PF12610

UniProt features (10 total): mutagenesis site 3, domain 2, region of interest 2, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75159-F1	62.60	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (3):

Position	Phenotype
406	abrogates the ability to induce egfr degradation.
484	abrogates the interaction with elob and eloc and the ability to suppress egfr signaling; when associated with f-488.
488	abrogates the interaction with elob and eloc and the ability to suppress egfr signaling; when associated with p-484.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-8951664	Neddylation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-449147	Signaling by Interleukins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 415 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_PROTEIN_TYROSINE_KINASE_ACTIVITY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY

GO Biological Process (15): epidermal growth factor receptor signaling pathway (GO:0007173), negative regulation of epidermal growth factor-activated receptor activity (GO:0007175), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), negative regulation of signal transduction (GO:0009968), protein ubiquitination (GO:0016567), cytokine-mediated signaling pathway (GO:0019221), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of interleukin-6 production (GO:0032715), intracellular signal transduction (GO:0035556), positive regulation of T-helper 1 cell differentiation (GO:0045627), negative regulation of T-helper 2 cell differentiation (GO:0045629), negative regulation of inflammatory response (GO:0050728), cellular response to low-density lipoprotein particle stimulus (GO:0071404), negative regulation of monocyte chemotactic protein-1 production (GO:0071638), vascular endothelial cell response to fluid shear stress (GO:0097699)

GO Molecular Function (3): epidermal growth factor receptor binding (GO:0005154), receptor tyrosine kinase binding (GO:0030971), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by Interleukins	1
Post-translational protein modification	1
Immune System	1
Cytokine Signaling in Immune system	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
ERBB signaling pathway	1
epidermal growth factor receptor activity	1
negative regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of protein tyrosine kinase activity	1
negative regulation of signaling receptor activity	1
cell surface receptor signaling pathway via STAT	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
protein modification by small protein conjugation	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
intracellular anatomical structure	1
positive regulation of immune effector process	1
T-helper 1 cell differentiation	1
positive regulation of T-helper cell differentiation	1
regulation of T-helper 1 cell differentiation	1
negative regulation of immune effector process	1
negative regulation of type 2 immune response	1
T-helper 2 cell differentiation	1
negative regulation of T-helper cell differentiation	1
regulation of T-helper 2 cell differentiation	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
response to lipoprotein particle	1
cellular response to lipoprotein particle stimulus	1
negative regulation of chemokine production	1
monocyte chemotactic protein-1 production	1
regulation of monocyte chemotactic protein-1 production	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOCS5	IL4R	P24394	914
SOCS5	JAK1	P23458	739
SOCS5	SOCS6	O14544	708
SOCS5	SOCS3	O14543	675
SOCS5	STAT1	P42224	666
SOCS5	SOCS4	Q8WXH5	593
SOCS5	CUL5	Q93034	547
SOCS5	ELOB	Q15370	533
SOCS5	STAT3	P40763	514
SOCS5	STAT6	P42226	501
SOCS5	ELOC	Q15369	471
SOCS5	JAK2	O60674	449
SOCS5	CISH	Q9NSE2	448
SOCS5	BCL6	P41182	442
SOCS5	SOCS1	O15524	431

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
CUL5	SOCS7	psi-mi:“MI:0914”(association)	0.640
RNF7	SOCS7	psi-mi:“MI:0914”(association)	0.530
SOCS5	KIT	psi-mi:“MI:0407”(direct interaction)	0.440
SOCS5	MET	psi-mi:“MI:0407”(direct interaction)	0.440
SOCS5	PPP5C	psi-mi:“MI:0915”(physical association)	0.400
CASP3	SOCS5	psi-mi:“MI:0915”(physical association)	0.370
SOCS5	TMBIM1	psi-mi:“MI:0915”(physical association)	0.370
ELOC	SOCS5	psi-mi:“MI:0915”(physical association)	0.370
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
	PIK3R2	psi-mi:“MI:0914”(association)	0.350

BioGRID (220): SOCS5 (Reconstituted Complex), SOCS5 (Affinity Capture-MS), SOCS5 (Affinity Capture-RNA), SOCS5 (Affinity Capture-MS), SOCS5 (Reconstituted Complex), SOCS5 (Reconstituted Complex), SOCS5 (Reconstituted Complex), SOCS5 (Reconstituted Complex), SOCS5 (Reconstituted Complex), SOCS5 (Reconstituted Complex), SOCS5 (Positive Genetic), SOCS5 (Affinity Capture-RNA), SOCS5 (Affinity Capture-RNA), SOCS5 (Affinity Capture-Western), STAT1 (Affinity Capture-Western)

ESM2 similar proteins: A0JM98, A1L1H3, A4Q9E8, A4Q9F0, A4Q9F6, A6NNM8, A7MBJ2, A8CVX7, D3ZF42, O54928, O75159, O88866, P51957, P57058, P59110, Q08D35, Q0P4M4, Q14679, Q29RN6, Q5NC05, Q5QJC4, Q5R978, Q5RHD1, Q5SUS0, Q5T7B8, Q63679, Q68UT7, Q6EEF3, Q6EMB2, Q6GQJ2, Q6IE81, Q6IE82, Q6IRU7, Q6NWW5, Q6P1H6, Q6P7W0, Q6PCM1, Q6PJP8, Q6ZPI0, Q7TP65

Diamond homologs: O00459, O08908, O14508, O14512, O14543, O14544, O15524, O35716, O35717, O35718, O46404, O54928, O55033, O70512, O75159, O88582, O88583, P23726, P23727, P26450, P27986, Q0VC91, Q29RN6, Q2HJ53, Q54RB7, Q5R685, Q5RCM6, Q5RDX2, Q62225, Q63787, Q63788, Q63789, Q64143, Q68AM8, Q7YRV6, Q861R0, Q8UUU2, Q8VHQ2, Q8WXH5, Q90X67

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SOCS5	“down-regulates quantity”	EGFR	binding
SOCS5	“up-regulates activity”	VCB-Cul2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	5	18.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	5	17.2×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

85 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

987 predictions. Top by Δscore:

Variant	Effect	Δscore
2:46719595:G:GG	donor_gain	0.9900
2:46732593:AAGG:A	acceptor_gain	0.9900
2:46719594:A:AG	donor_gain	0.9800
2:46732593:AAG:A	acceptor_gain	0.9800
2:46699694:G:GG	donor_gain	0.9700
2:46758260:ACCT:A	acceptor_gain	0.9600
2:46758510:T:A	acceptor_loss	0.9600
2:46758514:TTTA:T	acceptor_loss	0.9600
2:46758515:TTA:T	acceptor_loss	0.9600
2:46758516:TAG:T	acceptor_loss	0.9600
2:46758517:A:AG	acceptor_gain	0.9600
2:46758518:G:GA	acceptor_loss	0.9600
2:46758518:G:GG	acceptor_gain	0.9600
2:46699072:G:GT	donor_gain	0.9500
2:46699167:G:GT	donor_gain	0.9500
2:46699167:G:T	donor_gain	0.9500
2:46699447:ACGG:A	donor_loss	0.9500
2:46699448:CGGTG:C	donor_loss	0.9500
2:46699450:G:GC	donor_loss	0.9500
2:46699451:T:G	donor_loss	0.9500
2:46699689:GCTTA:G	donor_gain	0.9500
2:46719571:G:GT	donor_gain	0.9500
2:46699452:GA:G	donor_loss	0.9400
2:46732594:AGG:A	acceptor_gain	0.9400
2:46732595:GGG:G	acceptor_gain	0.9400
2:46758263:T:A	acceptor_gain	0.9300
2:46758518:GATT:G	acceptor_gain	0.9300
2:46699068:C:G	donor_gain	0.9200
2:46699108:CACG:C	donor_loss	0.9200
2:46699110:CGGTA:C	donor_loss	0.9200

AlphaMissense

3552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:46759168:T:C	L213S	1.000
2:46759182:T:C	C218R	1.000
2:46759184:C:G	C218W	1.000
2:46759188:T:C	F220L	1.000
2:46759189:T:C	F220S	1.000
2:46759190:T:A	F220L	1.000
2:46759190:T:G	F220L	1.000
2:46759218:T:A	W230R	1.000
2:46759218:T:C	W230R	1.000
2:46759219:G:C	W230S	1.000
2:46759220:G:C	W230C	1.000
2:46759220:G:T	W230C	1.000
2:46759228:T:A	I233N	1.000
2:46759333:G:C	R268T	1.000
2:46759333:G:T	R268M	1.000
2:46759334:G:C	R268S	1.000
2:46759334:G:T	R268S	1.000
2:46759345:T:A	I272N	1.000
2:46759353:G:A	G275R	1.000
2:46759353:G:C	G275R	1.000
2:46759353:G:T	G275W	1.000
2:46759620:G:C	D364H	1.000
2:46759621:A:T	D364V	1.000
2:46759677:T:A	W383R	1.000
2:46759677:T:C	W383R	1.000
2:46759679:G:C	W383C	1.000
2:46759679:G:T	W383C	1.000
2:46759680:G:A	G384R	1.000
2:46759680:G:C	G384R	1.000
2:46759681:G:A	G384E	1.000

dbSNP variants (sampled 300 via entrez): RS1000130717 (2:46746392 C>T), RS1000151299 (2:46724350 T>A), RS1000182764 (2:46745747 A>G), RS1000214155 (2:46716443 T>G), RS1000270215 (2:46737846 C>A), RS1000348054 (2:46704193 A>G,T), RS1000351133 (2:46755878 C>T), RS1000386774 (2:46719529 C>G), RS1000421731 (2:46754727 A>G), RS1000476668 (2:46762430 T>G), RS1000541162 (2:46744805 T>C), RS1000562919 (2:46704862 G>A), RS1000624205 (2:46710100 G>A), RS1000629647 (2:46703739 T>C), RS1000690162 (2:46714219 C>G)

Disease associations

OMIM: gene MIM:607094 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000817_53	Height	3.000000e-13
GCST001111_2	Current cigarettes per day in chronic obstructive pulmonary disease	3.000000e-06
GCST001111_4	Current cigarettes per day in chronic obstructive pulmonary disease	2.000000e-07
GCST002310_1	Pulse pressure (alcohol consumption interaction)	8.000000e-07
GCST002310_3	Pulse pressure (alcohol consumption interaction)	1.000000e-06
GCST004070_3	Cerebrospinal P-tau181p levels	2.000000e-06
GCST007293_106	Body fat distribution (arm fat ratio)	1.000000e-11
GCST007294_139	Body fat distribution (trunk fat ratio)	2.000000e-06
GCST007576_164	Chronotype	6.000000e-10
GCST008163_333	Height	1.000000e-08
GCST008363_19	Offspring birth weight	6.000000e-10
GCST90020029_802	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0004763	p-tau measurement
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, decreases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Indomethacin	decreases expression, affects cotreatment	2
Valproic Acid	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases methylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
1-aminomethylphosphonic acid	decreases expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Glyphosate	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8B6	Ubigene A-549 SOCS5 KO	Cancer cell line	Male
CVCL_D8VX	Ubigene HCT 116 SOCS5 KO	Cancer cell line	Male
CVCL_D9SK	Ubigene HEK293 SOCS5 KO	Transformed cell line	Female
CVCL_E0PL	Ubigene HeLa SOCS5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.