SOCS6

Summary

SOCS6 (suppressor of cytokine signaling 6, HGNC:16833) is a protein-coding gene on chromosome 18q22.2, encoding Suppressor of cytokine signaling 6 (O14544). 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 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.

Source: NCBI Gene 9306 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_004232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16833
Approved symbol	SOCS6
Name	suppressor of cytokine signaling 6
Location	18q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CIS4, SSI4, HSPC060, STATI4, STAI4, Cish4
Ensembl gene	ENSG00000170677
Ensembl biotype	protein_coding
OMIM	605118
Entrez	9306

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 25 protein_coding

ENST00000397942, ENST00000578377, ENST00000582322, ENST00000859907, ENST00000859908, ENST00000859909, ENST00000859910, ENST00000859911, ENST00000859912, ENST00000859913, ENST00000859914, ENST00000859915, ENST00000859916, ENST00000859917, ENST00000917314, ENST00000917315, ENST00000917316, ENST00000917317, ENST00000955156, ENST00000955157, ENST00000955158, ENST00000955159, ENST00000955160, ENST00000955161, ENST00000955162

RefSeq mRNA: 1 — MANE Select: NM_004232 NM_004232

CCDS: CCDS11998

Canonical transcript exons

ENST00000397942 — 2 exons

Exon	Start	End
ENSE00001162688	70289045	70289090
ENSE00001530862	70324543	70330199

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 91.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7037 / max 186.5970, expressed in 1769 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139683	15.7037	1769
170715	8.3723	1680
170712	1.3366	848
170716	0.3947	176
170714	0.2620	117
170713	0.2323	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	91.53	gold quality
biceps brachii	UBERON:0001507	91.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.96	gold quality
jejunal mucosa	UBERON:0000399	90.53	gold quality
oral cavity	UBERON:0000167	90.28	gold quality
colonic mucosa	UBERON:0000317	89.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.78	gold quality
jejunum	UBERON:0002115	89.50	gold quality
heart right ventricle	UBERON:0002080	87.96	gold quality
caput epididymis	UBERON:0004358	87.52	gold quality
bronchial epithelial cell	CL:0002328	87.34	gold quality
islet of Langerhans	UBERON:0000006	87.29	gold quality
calcaneal tendon	UBERON:0003701	86.74	gold quality
cauda epididymis	UBERON:0004360	86.54	gold quality
pigmented layer of retina	UBERON:0001782	86.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.99	gold quality
amniotic fluid	UBERON:0000173	85.70	gold quality
inferior vagus X ganglion	UBERON:0005363	85.68	gold quality
stromal cell of endometrium	CL:0002255	85.45	gold quality
cortical plate	UBERON:0005343	85.40	gold quality
corpus callosum	UBERON:0002336	85.18	gold quality
corpus epididymis	UBERON:0004359	85.01	gold quality
rectum	UBERON:0001052	85.00	gold quality
seminal vesicle	UBERON:0000998	84.85	gold quality
subthalamic nucleus	UBERON:0001906	84.85	gold quality
endometrium	UBERON:0001295	84.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.61	gold quality
gingiva	UBERON:0001828	84.58	gold quality
gall bladder	UBERON:0002110	84.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	322.71
E-ANND-3	yes	4.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1, STAT5A, STAT5B

miRNA regulators (miRDB)

295 targeting SOCS6, 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-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 31)

• HOIL-1 expression stabilizes SOCS6 and induces the ubiquitination and degradation of proteins associated with SOCS6 (PMID:16643902)
• These observations suggest that Erk activation may be correlated in the cells with high expression of SOCS6. (PMID:17210122)
• These observations suggest that SOCS6 is composed of at least two functional domains required for its biological role in localizing and degrading Stat3 in the nucleus. (PMID:17603019)
• Data support the importance of loss-of-function of SOCS6 as a frequent event in gastric tumorigenesis. (PMID:19646809)
• Study demonstrated that hypermethylation of the SOCS6 promoter is one of the mechanisms for the epigenetic regulation of SOCS6 expression. (PMID:19716864)
• These results establish that SOCS-6 acts as a negative regulator of T cell activation by promoting ubiquitin-dependent proteolysis of p56(lck). (PMID:20007709)
• SOCS6 has ubiquitin ligase activity toward c-KIT (PMID:21030588)
• 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)
• Reduced copy number and mRNA expression of SOCS6 are associated with disease recurrence in primary lung squamous cell carcinoma and may be useful prognostic biomarkers. (PMID:22363434)
• SOCS6 negatively regulates Flt3 activation, the downstream Erk signaling pathway, and cell proliferation. (PMID:22952242)
• Results show that SOCS6 forms complex with DRP1 and the mitochondrial phosphatase PGAM5, attenuates DRP1 phosphorylation, and promotes DRP1 mitochondrial translocation. (PMID:22955947)
• SOCS2 and SOCS6 expression are remarkably reduced in hepatocellular carcinoma and correlate with aggressive tumor progression and poor prognosis (PMID:23475171)
• Studied both the function of upregulated miR-424-5p in pancreatic cancer and how downstream suppressor of cytokine-induced signaling 6 (SOCS6) is negatively regulated by miR-424-5p. (PMID:23653113)
• miR-17-5p might function as a pro-proliferative factor by repressing SOCS6 in gastric cancer (PMID:24801601)
• Stage-independent downregulation of SOCS2 and SOCS6 correlate with disease-free survival in colorectal cancer. (PMID:25025962)
• miR-142-3p regulates NPC development by down-regulating SOCS6 expression and suggest that modulation of miR-142-3p expression could be a therapeutic strategy for NPC (PMID:26183850)
• our results describe for the first time the role of miR-494-3p during normal hematopoietic stem/progenitor cells differentiation and suggest that its increased expression, and the subsequent downregulation of its target SOCS6, might contribute to the megakaryocyte hyperplasia commonly observed in primary myelofibrosis patients. (PMID:28423484)
• Results indicate that similar to PTEN pseudogene (PTENP1), suppressor of cytokine signaling 6 protein (SOCS6) expression was also significantly lower in esophageal squamous cell carcinoma (ESCC) samples. (PMID:28731203)
• Together, our data provide important evidence for miR-19 mediated SOCS6 in OS growth and revealed miR-19/SOCS6/JAK2/STAT3 pathway as a potential therapeutic strategy for OS patients. (PMID:28986253)
• Low SOCS6 expression is associated with Prostate Cancer. (PMID:29295692)
• Study is the first to illustrate that miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate NSCLC cell proliferation and apoptosis, and is a potential biomarker and therapeutic target for NSCLC. (PMID:30737371)
• microRNA-454 promotes liver tumor-initiating cell expansion by regulating SOCS6. (PMID:32165166)
• miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6. (PMID:32587662)
• Inhibition of SOCS6 confers radioresistance in esophageal squamous cell carcinoma. (PMID:33689885)
• Circ_0085289 Alleviates the Progression of Periodontitis by Regulating let-7f-5p/SOCS6 Pathway. (PMID:33710445)
• Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6. (PMID:34100174)
• Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis. (PMID:34895274)
• MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment. (PMID:35038704)
• Methyltransferase-like 3 facilitates lung cancer progression by accelerating m6A methylation-mediated primary miR-663 processing and impeding SOCS6 expression. (PMID:35907010)
• Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways. (PMID:37972389)
• Publisher Correction: MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells. (PMID:38766781)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	socs6b	ENSDARG00000015863
danio_rerio	socs6a	ENSDARG00000058565
mus_musculus	Socs6	ENSMUSG00000056153
rattus_norvegicus	Socs6	ENSRNOG00000038212
drosophila_melanogaster	Socs44A	FBGN0033266
drosophila_melanogaster	Socs36E	FBGN0041184

Paralogs (7): CISH (ENSG00000114737), SOCS2 (ENSG00000120833), SOCS5 (ENSG00000171150), SOCS4 (ENSG00000180008), SOCS3 (ENSG00000184557), SOCS1 (ENSG00000185338), SOCS7 (ENSG00000274211)

Protein

Protein identifiers

Suppressor of cytokine signaling 6 — O14544 (reviewed: O14544)

Alternative names: Cytokine-inducible SH2 protein 4, Suppressor of cytokine signaling 4

All UniProt accessions (2): O14544, J3KTM7

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. Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor.

Subunit / interactions. Interacts with RBCK1. Interacts with phosphorylated IRS4. Interacts with PIM3. Interacts with KIT (phosphorylated).

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

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_004223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001496	SOCS_box	Domain
IPR035865	SOCS6_SH2	Domain
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037345	SOCS6_SOCS	Domain

Pfam: PF00017, PF07525

UniProt features (17 total): strand 6, helix 3, domain 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2VIF	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14544-F1	54.84	0.15

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1433559	Regulation of KIT signaling
R-HSA-8951664	Neddylation
R-HSA-9706369	Negative regulation of FLT3
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9607240	FLT3 Signaling

MSigDB gene sets: 470 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, AGGAAGC_MIR5163P, GOBP_REGULATION_OF_PROTEIN_TYROSINE_KINASE_ACTIVITY, ACTACCT_MIR196A_MIR196B, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GCM_GSPT1, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01

GO Biological Process (8): defense response (GO:0006952), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), negative regulation of signal transduction (GO:0009968), proteasomal protein catabolic process (GO:0010498), protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556), regulation of growth (GO:0040008), negative regulation of T cell activation (GO:0050868)

GO Molecular Function (2): signaling adaptor activity (GO:0035591), protein binding (GO:0005515)

GO Cellular Component (3): immunological synapse (GO:0001772), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Signaling by SCF-KIT	1
Post-translational protein modification	1
FLT3 Signaling	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Metabolism of proteins	1
Signal Transduction	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
intracellular anatomical structure	2
response to stress	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 catabolic process	1
protein modification by small protein conjugation	1
growth	1
regulation of biological process	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
protein-macromolecule adaptor activity	1
binding	1
plasma membrane	1
cytoplasm	1

Protein interactions and networks

STRING

906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOCS6	ELOC	Q15369	872
SOCS6	ELOB	Q15370	775
SOCS6	KLHL1	Q9NR64	764
SOCS6	CUL5	Q93034	732
SOCS6	PGAM5	Q96HS1	725
SOCS6	DSC2	Q02487	724
SOCS6	DSC3	Q14574	723
SOCS6	SOCS5	O75159	708
SOCS6	CALB1	P05937	638
SOCS6	ASB9	Q96DX5	593
SOCS6	EGFR	P00533	587
SOCS6	IRS4	O14654	558
SOCS6	H3BTC1	H3BTC1	545
SOCS6	RTTN	Q86VV8	541
SOCS6	SOCS2	O14508	497
SOCS6	TAF1	P21675	497

IntAct

100 interactions, top by confidence:

A	B	Type	Score
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
CUL5	SOCS6	psi-mi:“MI:0914”(association)	0.640
SOCS6	ARIH2	psi-mi:“MI:0914”(association)	0.620
SOCS6	ARIH2	psi-mi:“MI:0915”(physical association)	0.620
SOCS6	TXK	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	ERN1	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
FKBP1A	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	GSN	psi-mi:“MI:0915”(physical association)	0.560
HSPA2	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
PRKN	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
SARS1	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	SOCS6	psi-mi:“MI:0915”(physical association)	0.560
SOCS6	TARDBP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (234): SOCS6 (Two-hybrid), TCEB1 (Affinity Capture-MS), PLEC (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), PIK3R3 (Affinity Capture-MS), POLA1 (Affinity Capture-MS), ACACA (Affinity Capture-MS), ARIH2 (Affinity Capture-MS), USP1 (Affinity Capture-MS), SAV1 (Affinity Capture-MS), KIAA0232 (Affinity Capture-MS), FAM83H (Affinity Capture-MS), MADD (Affinity Capture-MS)

ESM2 similar proteins: A0JMD2, A2ANU3, A7J1T0, A7J1T2, B0S6S9, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14544, O43283, P57773, Q02223, Q06190, Q08DM6, Q14CH0, Q1HKZ5, Q1X8D7, Q2PFD7, Q3TEL6, Q3UVY1, Q4R532, Q58DZ9, Q5R8X7, Q5RA75, Q5RCM6, Q5RD34, Q5RJX2, Q5SW75, Q5TZE2, Q5VUB5, Q60610, Q6IRN6, Q6NRK3, Q6P995, Q6PUR7, Q76I76, Q86SP6, Q8BIA3, Q8BQU7

Diamond homologs: G5ECJ6, O00459, O08908, O14508, O14544, O35717, O46404, O88582, P00519, P00520, P00521, P10447, P14234, P15498, P23726, P23727, P26450, P27986, P41242, P41243, P42679, P42684, P54100, P62993, P62994, Q08012, Q08DN7, Q45FX5, Q4JIM5, Q54RB7, Q5R4J7, Q5R685, Q5RCM6, Q60631, Q62662, Q63787, Q63788, Q63789, Q64143, Q6P6U0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SOCS6	down-regulates	KIT	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Constitutive Signaling by Aberrant PI3K in Cancer	8	28.2×	1e-07
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	21.5×	3e-07
PIP3 activates AKT signaling	9	16.7×	3e-07
RAF/MAP kinase cascade	7	11.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process	7	12.7×	3e-04
positive regulation of MAPK cascade	5	9.8×	6e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	9.6×	6e-03
positive regulation of cell migration	6	9.0×	3e-03
protein ubiquitination	7	7.1×	3e-03
positive regulation of gene expression	7	6.6×	4e-03
negative regulation of apoptotic process	7	5.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1565 predictions. Top by Δscore:

Variant	Effect	Δscore
14:55027453:T:G	donor_gain	1.0000
18:70289089:GG:G	donor_gain	1.0000
18:70289089:GGGT:G	donor_loss	1.0000
18:70289090:GG:G	donor_gain	1.0000
18:70289091:GT:G	donor_loss	1.0000
18:70289086:TCCGG:T	donor_gain	0.9900
18:70289088:CGG:C	donor_gain	0.9900
18:70289089:GGG:G	donor_gain	0.9900
18:70289091:G:GG	donor_gain	0.9900
18:70289092:T:G	donor_loss	0.9900
18:70324541:A:AG	acceptor_gain	0.9900
18:70324542:G:GG	acceptor_gain	0.9900
14:55031861:A:G	acceptor_gain	0.9800
14:55042950:A:AG	acceptor_gain	0.9800
14:55042951:G:GG	acceptor_gain	0.9800
18:70289067:G:GT	donor_gain	0.9800
18:70289087:CCGG:C	donor_gain	0.9800
18:70305320:A:AG	acceptor_gain	0.9800
18:70305321:G:GG	acceptor_gain	0.9800
18:70305411:G:GG	donor_gain	0.9800
18:70319565:T:TA	donor_gain	0.9800
18:70319566:A:AA	donor_gain	0.9800
14:55033371:GTGTT:G	donor_gain	0.9700
14:55033372:TGTTT:T	donor_gain	0.9700
14:55042947:TTTA:T	acceptor_loss	0.9700
14:55042949:TA:T	acceptor_loss	0.9700
14:55042950:A:T	acceptor_loss	0.9700
14:55043003:GCA:G	donor_gain	0.9700
18:70305321:GTT:G	acceptor_gain	0.9700
18:70319554:AAT:A	donor_gain	0.9700

AlphaMissense

3524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:70325795:T:C	L376P	1.000
18:70325818:T:A	W384R	1.000
18:70325818:T:C	W384R	1.000
18:70325820:G:C	W384C	1.000
18:70325820:G:T	W384C	1.000
18:70325821:T:C	Y385H	1.000
18:70325824:T:A	W386R	1.000
18:70325824:T:C	W386R	1.000
18:70325826:G:C	W386C	1.000
18:70325826:G:T	W386C	1.000
18:70325827:G:A	G387R	1.000
18:70325827:G:C	G387R	1.000
18:70325828:G:A	G387E	1.000
18:70325828:G:T	G387V	1.000
18:70325848:G:C	A394P	1.000
18:70325861:T:A	L398Q	1.000
18:70325861:T:C	L398P	1.000
18:70325879:G:A	G404D	1.000
18:70325879:G:T	G404V	1.000
18:70325884:T:C	F406L	1.000
18:70325885:T:C	F406S	1.000
18:70325886:T:A	F406L	1.000
18:70325886:T:G	F406L	1.000
18:70325888:T:A	L407H	1.000
18:70325888:T:C	L407P	1.000
18:70325894:G:C	R409P	1.000
18:70325896:G:C	D410H	1.000
18:70325896:G:T	D410Y	1.000
18:70325897:A:C	D410A	1.000
18:70325897:A:G	D410G	1.000

dbSNP variants (sampled 300 via entrez): RS1000034039 (18:70304932 C>A,T), RS1000060779 (18:70307226 C>A,T), RS1000112514 (18:70317140 G>A,C), RS1000180750 (18:70313613 A>G,T), RS1000357245 (18:70319467 T>A), RS1000371018 (18:70306965 T>A), RS1000382401 (18:70328604 A>G), RS1000397204 (18:70292444 G>A), RS1000512911 (18:70323069 G>A), RS1000542824 (18:70292963 A>C), RS1000615489 (18:70296482 G>A), RS1000641153 (18:70313940 T>G), RS1000648502 (18:70296655 G>C), RS1000676509 (18:70307944 T>C), RS1000781701 (18:70301986 G>A,T)

Disease associations

OMIM: gene MIM:605118 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000144_8	Systemic lupus erythematosus	6.000000e-06
GCST003542_197	Night sleep phenotypes	7.000000e-06
GCST005912_2	Type 2 diabetes	3.000000e-06
GCST006479_64	Diverticular disease	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	5
trichostatin A	decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
2-palmitoylglycerol	increases 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
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Amiodarone	increases expression	1
Arsenicals	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Diclofenac	affects expression	1
Doxorubicin	affects 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_D8B7	Ubigene A-549 SOCS6 KO	Cancer cell line	Male
CVCL_D8VY	Ubigene HCT 116 SOCS6 KO	Cancer cell line	Male
CVCL_D9SL	Ubigene HEK293 SOCS6 KO	Transformed cell line	Female
CVCL_E0PM	Ubigene HeLa SOCS6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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