ASB8

Summary

ASB8 (ankyrin repeat and SOCS box containing 8, HGNC:17183) is a protein-coding gene on chromosome 12q13.11, encoding Ankyrin repeat and SOCS box protein 8 (Q9H765). May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Predicted to be involved in intracellular signal transduction and protein ubiquitination. Predicted to be located in cytosol.

Source: NCBI Gene 140461 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_024095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17183
Approved symbol	ASB8
Name	ankyrin repeat and SOCS box containing 8
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC5540, FLJ21255
Ensembl gene	ENSG00000177981
Ensembl biotype	protein_coding
OMIM	615053
Entrez	140461

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000317697, ENST00000535055, ENST00000535988, ENST00000536071, ENST00000536549, ENST00000536938, ENST00000536953, ENST00000537754, ENST00000539464, ENST00000539503, ENST00000539528, ENST00000539865, ENST00000540143, ENST00000540212, ENST00000540782, ENST00000545791, ENST00000548228, ENST00000629941, ENST00000873811, ENST00000873812, ENST00000938966, ENST00000938967, ENST00000942522, ENST00000942523

RefSeq mRNA: 7 — MANE Select: NM_024095 NM_001319296, NM_001319297, NM_001319298, NM_001319299, NM_001319300, NM_001319301, NM_024095

CCDS: CCDS81686, CCDS8761

Canonical transcript exons

ENST00000317697 — 4 exons

Exon	Start	End
ENSE00001218337	48153368	48153529
ENSE00002222871	48157459	48157515
ENSE00002228904	48147789	48149998
ENSE00003636880	48151201	48151305

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1043 / max 153.3998, expressed in 1802 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130727	17.3111	1798
130728	1.7543	974
130729	0.7991	457
130726	0.1906	83
130725	0.0491	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.22	gold quality
muscle of leg	UBERON:0001383	97.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.89	gold quality
muscle organ	UBERON:0001630	97.49	gold quality
biceps brachii	UBERON:0001507	97.12	gold quality
vastus lateralis	UBERON:0001379	96.57	gold quality
skeletal muscle tissue	UBERON:0001134	96.52	gold quality
quadriceps femoris	UBERON:0001377	96.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.32	gold quality
body of tongue	UBERON:0011876	96.30	gold quality
oocyte	CL:0000023	95.34	gold quality
diaphragm	UBERON:0001103	95.03	gold quality
deltoid	UBERON:0001476	95.03	gold quality
muscle tissue	UBERON:0002385	94.88	gold quality
olfactory bulb	UBERON:0002264	93.81	gold quality
left ventricle myocardium	UBERON:0006566	93.73	gold quality
tibialis anterior	UBERON:0001385	93.66	gold quality
tongue	UBERON:0001723	93.53	gold quality
apex of heart	UBERON:0002098	93.36	gold quality
heart left ventricle	UBERON:0002084	93.13	gold quality
cardiac ventricle	UBERON:0002082	93.07	gold quality
monocyte	CL:0000576	92.72	gold quality
cortical plate	UBERON:0005343	92.70	gold quality
mononuclear cell	CL:0000842	92.61	gold quality
leukocyte	CL:0000738	92.52	gold quality
cerebellar hemisphere	UBERON:0002245	92.42	gold quality
cerebellar cortex	UBERON:0002129	92.41	gold quality
secondary oocyte	CL:0000655	91.99	gold quality
islet of Langerhans	UBERON:0000006	91.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting ASB8, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745

Literature-anchored findings (GeneRIF, showing 2)

• molecular cloning and characterization of the human ASB-8 gene (PMID:12559969)
• E3 ubiquitin ligase ankyrin repeat and SOCS box-containing 8(ASB8) interacted with TBK1/IKKi and phosphorylation modification of ASB8 at site of Ser17 to further strengthen its ubiquitination activity were verified. Phosphorylated ASB8 accelerates K48-linked ubiquitination and degradation of TBK1/IKKi, which further reduces phosphorylation level of IRF3 and inhibits production of IFN-beta. (PMID:32298923)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb8	ENSDARG00000003383
mus_musculus	Asb8	ENSMUSG00000048175
rattus_norvegicus	Asb8	ENSRNOG00000075267
caenorhabditis_elegans		WBGENE00011270

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 8 — Q9H765 (reviewed: Q9H765)

All UniProt accessions (10): F5GYF0, F5GZZ3, F5H023, F5H243, F5H5S9, F5H6A7, F5H772, F5H7B4, F8VS92, Q9H765

UniProt curated annotations — full annotation on UniProt →

Function. May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits IFN-beta production through the IRF3 signaling pathway by targeting TBK1 via ‘Lys-48’-linked ubiquitination, leading to its proteasomal degradation.

Subunit / interactions. Interacts with TBK1; this interaction promotes TBK1 proteasomal degradation.

Subcellular location. Cytoplasm.

Tissue specificity. Highest level of expression in skeletal muscle. Also expressed in heart, brain, placenta, liver, kidney and pancreas.

Post-translational modifications. Phosphorylated by TBK1.

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

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ankyrin SOCS box (ASB) family.

RefSeq proteins (7): NP_001306225, NP_001306226, NP_001306227, NP_001306228, NP_001306229, NP_001306230, NP_077000* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001496	SOCS_box	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037332	ASB8_SOCS	Domain

Pfam: PF07525, PF12796, PF13637

UniProt features (8 total): repeat 4, chain 1, domain 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9OGD	ELECTRON MICROSCOPY	2.49
9OGB	ELECTRON MICROSCOPY	3.25
9OGE	ELECTRON MICROSCOPY	3.28
9OGC	ELECTRON MICROSCOPY	3.37
9OGF	ELECTRON MICROSCOPY	4.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H765-F1	88.41	0.63

Functional residue map

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

Post-translational modifications (1): 17

Mutagenesis-validated functional residues (1):

Position	Phenotype
17	almost complete lost of phosphorylation by tbk1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 107 (showing top): TGCGCANK_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, SCGGAAGY_ELK1_02, ER_Q6_02, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KASLER_HDAC7_TARGETS_1_UP, LIM_MAMMARY_STEM_CELL_DN, REACTOME_NEDDYLATION, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, ATF6_TARGET_GENES

GO Biological Process (2): protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
protein modification by small protein conjugation	1
signal transduction	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB8	RNF215	Q9Y6U7	552
ASB8	FAM217B	Q9NTX9	542
ASB8	CDC40	O60508	526
ASB8	PRR15L	Q9BU68	479
ASB8	LRRC30	A6NM36	463
ASB8	LRRC20	Q8TCA0	459
ASB8	LRRC14B	A6NHZ5	429
ASB8	ZNF646	O15015	411
ASB8	SCRN3	Q0VDG4	397
ASB8	DRC11L	A6NCM1	392
ASB8	UBOX5	O94941	391
ASB8	LRRC28	Q86X40	390
ASB8	RDM1	Q8NG50	385
ASB8	AKAP1	Q92667	385
ASB8	SDR39U1	Q9NRG7	364

IntAct

22 interactions, top by confidence:

A	B	Type	Score
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
VHL	ASB8	psi-mi:“MI:0915”(physical association)	0.560
ELOC	ASB8	psi-mi:“MI:0915”(physical association)	0.550
ASB8	CUL5	psi-mi:“MI:0914”(association)	0.530
ASB8	USP33	psi-mi:“MI:0915”(physical association)	0.400
ASB8	RIN3	psi-mi:“MI:0915”(physical association)	0.370
ASB8	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
HOXD4	ASB8	psi-mi:“MI:0915”(physical association)	0.370
MCM7	ASB8	psi-mi:“MI:0915”(physical association)	0.370
ASB8	RCN1	psi-mi:“MI:0915”(physical association)	0.370
ASB8	SERTAD1	psi-mi:“MI:0915”(physical association)	0.370
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
ASB8	NPAT	psi-mi:“MI:0914”(association)	0.350
RNF7	SOCS2	psi-mi:“MI:0914”(association)	0.350
ASB8	CUL4B	psi-mi:“MI:0914”(association)	0.350
ASB8	TRIM11	psi-mi:“MI:0914”(association)	0.350
CELF1	ASB8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): ASB8 (Affinity Capture-RNA), ASB8 (Affinity Capture-RNA), CUL5 (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), NPAT (Affinity Capture-MS), TRIM11 (Affinity Capture-MS), AMBRA1 (Affinity Capture-MS), ASB8 (Two-hybrid), CUL5 (Affinity Capture-MS), IARS2 (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), NPAT (Affinity Capture-MS), TRIM11 (Affinity Capture-MS), AMBRA1 (Affinity Capture-MS), RUFY3 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ0, A6NHY2, A7E2S9, C7B178, D3J162, G5E8K5, P42570, P42773, P53355, Q08E43, Q10311, Q14DN9, Q18297, Q2T9W8, Q3EC11, Q4R3S3, Q4R544, Q4UJC4, Q4UJJ2, Q5EFR1, Q5I126, Q5I148, Q5I155, Q5I159, Q5I160, Q5R6D7, Q5RCK5, Q5TYM7, Q5VYY1, Q60772, Q60773, Q6XJU9, Q80YE7, Q86WC6, Q91ZT9, Q91ZU0, Q92527, Q9BGT9, Q9CQM6, Q9D119

Diamond homologs: Q08E43, Q4R544, Q5R6D7, Q91ZT9, Q9H765

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IKBKB	“up-regulates activity”	ASB8	phosphorylation
ASB8	“down-regulates quantity by destabilization”	IKBKB	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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	6	17.8×	4e-05
Antigen processing: Ubiquitination & Proteasome degradation	5	11.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	8	16.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

962 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48149994:TTCAC:T	acceptor_gain	1.0000
12:48149995:TCAC:T	acceptor_gain	1.0000
12:48149996:CAC:C	acceptor_gain	1.0000
12:48149996:CACC:C	acceptor_gain	1.0000
12:48149996:CACCT:C	acceptor_loss	1.0000
12:48149999:C:CC	acceptor_gain	1.0000
12:48149999:CT:C	acceptor_loss	1.0000
12:48150000:T:A	acceptor_loss	1.0000
12:48151195:CATTA:C	donor_loss	1.0000
12:48151196:ATTAC:A	donor_loss	1.0000
12:48151197:TTA:T	donor_loss	1.0000
12:48151198:TACC:T	donor_loss	1.0000
12:48151199:A:AC	donor_gain	1.0000
12:48151200:C:CC	donor_gain	1.0000
12:48151200:CCT:C	donor_gain	1.0000
12:48151302:CTCC:C	acceptor_gain	1.0000
12:48151303:TCC:T	acceptor_gain	1.0000
12:48151304:CC:C	acceptor_gain	1.0000
12:48151304:CCC:C	acceptor_gain	1.0000
12:48151304:CCCTG:C	acceptor_loss	1.0000
12:48151305:CC:C	acceptor_gain	1.0000
12:48151305:CCTG:C	acceptor_loss	1.0000
12:48151306:C:A	acceptor_loss	1.0000
12:48151306:C:CC	acceptor_gain	1.0000
12:48151512:T:TA	donor_gain	1.0000
12:48157457:A:AC	donor_gain	1.0000
12:48157458:C:CC	donor_gain	1.0000
12:48149997:AC:A	acceptor_gain	0.9900
12:48149998:CC:C	acceptor_gain	0.9900
12:48150001:G:GC	acceptor_gain	0.9900

AlphaMissense

1858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48149790:T:A	D148V	0.999
12:48149973:C:G	R87P	0.999
12:48149985:T:A	D83V	0.999
12:48151252:A:C	C61W	0.999
12:48151253:C:T	C61Y	0.999
12:48151268:G:T	P56H	0.999
12:48149765:G:C	S156R	0.998
12:48149765:G:T	S156R	0.998
12:48149767:T:G	S156R	0.998
12:48149852:A:C	F127L	0.998
12:48149852:A:T	F127L	0.998
12:48149854:A:G	F127L	0.998
12:48149889:T:A	D115V	0.998
12:48149890:C:G	D115H	0.998
12:48149953:C:G	A94P	0.998
12:48149955:G:T	A93E	0.998
12:48149964:A:T	L90H	0.998
12:48149984:A:C	D83E	0.998
12:48149984:A:T	D83E	0.998
12:48149985:T:G	D83A	0.998
12:48149986:C:A	D83Y	0.998
12:48149986:C:G	D83H	0.998
12:48151254:A:G	C61R	0.998
12:48149761:C:G	A158P	0.997
12:48149764:A:G	W157R	0.997
12:48149764:A:T	W157R	0.997
12:48149772:G:C	P154R	0.997
12:48149778:T:A	D152V	0.997
12:48149778:T:C	D152G	0.997
12:48149791:C:G	D148H	0.997

dbSNP variants (sampled 300 via entrez): RS1000098926 (12:48152277 T>C), RS1000163306 (12:48150419 T>C), RS1000552689 (12:48152561 A>C,G), RS1000763870 (12:48152116 C>G,T), RS1000867697 (12:48158797 C>G), RS1000915136 (12:48158573 T>A,C), RS1000993443 (12:48151440 C>A), RS1001114342 (12:48152285 A>G), RS1001160915 (12:48150951 A>G), RS1001833642 (12:48154130 A>C), RS1002609055 (12:48148336 A>G), RS1002719154 (12:48155154 G>C), RS1002965311 (12:48148716 T>C), RS1003659737 (12:48148943 C>T), RS1003668695 (12:48157126 T>A,C)

Disease associations

OMIM: gene MIM:615053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Urethane	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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