ASB6

Summary

ASB6 (ankyrin repeat and SOCS box containing 6, HGNC:17181) is a protein-coding gene on chromosome 9q34.11, encoding Ankyrin repeat and SOCS box protein 6 (Q9NWX5). Probable 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.

The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 140459 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total — 2 pathogenic
• MANE Select transcript: NM_017873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17181
Approved symbol	ASB6
Name	ankyrin repeat and SOCS box containing 6
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000148331
Ensembl biotype	protein_coding
OMIM	615051
Entrez	140459

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000277458, ENST00000277459, ENST00000450050, ENST00000936076

RefSeq mRNA: 3 — MANE Select: NM_017873 NM_001202403, NM_017873, NM_177999

CCDS: CCDS6924, CCDS6925, CCDS75919

Canonical transcript exons

ENST00000277458 — 6 exons

Exon	Start	End
ENSE00000984420	129640541	129640722
ENSE00000984421	129639402	129639508
ENSE00000984422	129639202	129639310
ENSE00002232308	129641887	129642151
ENSE00003544195	129638573	129638659
ENSE00003612082	129634605	129638457

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 88.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9214 / max 133.8733, expressed in 1789 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102750	10.9214	1789

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	88.03	gold quality
right frontal lobe	UBERON:0002810	85.92	gold quality
mucosa of stomach	UBERON:0001199	85.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.11	gold quality
prefrontal cortex	UBERON:0000451	85.10	gold quality
left adrenal gland cortex	UBERON:0035825	84.95	gold quality
middle temporal gyrus	UBERON:0002771	84.76	gold quality
left adrenal gland	UBERON:0001234	84.71	gold quality
right adrenal gland cortex	UBERON:0035827	84.71	gold quality
cerebellar hemisphere	UBERON:0002245	84.60	gold quality
cerebellar cortex	UBERON:0002129	84.53	gold quality
anterior cingulate cortex	UBERON:0009835	84.42	gold quality
cingulate cortex	UBERON:0003027	84.41	gold quality
right adrenal gland	UBERON:0001233	84.25	gold quality
skin of leg	UBERON:0001511	84.25	gold quality
lower esophagus mucosa	UBERON:0035834	83.95	gold quality
adrenal cortex	UBERON:0001235	83.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.78	gold quality
cerebellum	UBERON:0002037	83.48	gold quality
frontal cortex	UBERON:0001870	83.40	gold quality
frontal lobe	UBERON:0016525	83.40	gold quality
neocortex	UBERON:0001950	83.27	gold quality
mucosa of transverse colon	UBERON:0004991	83.24	gold quality
stromal cell of endometrium	CL:0002255	83.23	gold quality
body of stomach	UBERON:0001161	83.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.03	gold quality
metanephros cortex	UBERON:0010533	82.94	gold quality
skin of abdomen	UBERON:0001416	82.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.73	gold quality
adrenal gland	UBERON:0002369	82.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting ASB6, 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-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Literature-anchored findings (GeneRIF, showing 1)

• m[6]A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation. (PMID:36446779)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb6	ENSDARG00000007125
mus_musculus	Asb6	ENSMUSG00000039483
rattus_norvegicus	Asb6	ENSRNOG00000024786

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 6 — Q9NWX5 (reviewed: Q9NWX5)

All UniProt accessions (2): Q9NWX5, F6TX30

UniProt curated annotations — full annotation on UniProt →

Function. Probable 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. May play a role in the regulation of cell proliferation and autophagy by promoting the ubiquitination and degradation of SQSTM1.

Subunit / interactions. Binds APS. Identified in a complex with ELOB and ELOC. Interacts with CUL5 and RNF7. Interacts with SQSTM1.

Subcellular location. Cytoplasm.

Post-translational modifications. Ubiquitinated by RNF41; leading to proteasomal degradation.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWX5-1	1	yes
Q9NWX5-2	2

RefSeq proteins (3): NP_001189332, NP_060343, NP_821066 (=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
IPR037327	ASB6_SOCS	Domain

Pfam: PF07525, PF12796, PF13637

UniProt features (9 total): repeat 6, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWX5-F1	87.02	0.60

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: 124 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MARTINEZ_RB1_TARGETS_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GCM_NF2, MARTINEZ_RB1_AND_TP53_TARGETS_UP, SCGGAAGY_ELK1_02, STEIN_ESRRA_TARGETS_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KASLER_HDAC7_TARGETS_1_UP, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, CSR_LATE_UP.V1_UP

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

1526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB6	CUL5	Q93034	754
ASB6	ASB7	Q9H672	633
ASB6	ASB1	Q9Y576	537
ASB6	KLHL42	Q9P2K6	528
ASB6	ASB11	Q8WXH4	508
ASB6	SPATA9	Q9BWV2	495
ASB6	ASB4	Q9Y574	491
ASB6	RNF34	Q969K3	486
ASB6	TRIM37	O94972	473
ASB6	RBX1	P62877	470
ASB6	ASB9	Q96DX5	469
ASB6	CUL2	Q13617	466
ASB6	FBXO46	Q6PJ61	464
ASB6	SCARB2	Q14108	458
ASB6	ARRB1	P49407	447
ASB6	DAB2	P98082	447

IntAct

94 interactions, top by confidence:

A	B	Type	Score
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
ASB6	RNF41	psi-mi:“MI:0915”(physical association)	0.830
RNF41	ASB6	psi-mi:“MI:0915”(physical association)	0.830
ASB6	CUL5	psi-mi:“MI:0915”(physical association)	0.780
CUL5	ASB6	psi-mi:“MI:0915”(physical association)	0.780
POLR2A	ASB6	psi-mi:“MI:0915”(physical association)	0.740
RNF7	ASB6	psi-mi:“MI:0915”(physical association)	0.670
CUL5	SOCS6	psi-mi:“MI:0914”(association)	0.640
ASB6	ELOC	psi-mi:“MI:0914”(association)	0.640
FAM9B	ASB6	psi-mi:“MI:0915”(physical association)	0.560
ASB6	L3MBTL3	psi-mi:“MI:0915”(physical association)	0.560
ASB6	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
L3MBTL3	ASB6	psi-mi:“MI:0915”(physical association)	0.560
	ASB6	psi-mi:“MI:0915”(physical association)	0.560
SH2B2	ASB6	psi-mi:“MI:0915”(physical association)	0.560
MOS	ASB6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB42	ASB6	psi-mi:“MI:0915”(physical association)	0.560
TARS2	ASB6	psi-mi:“MI:0915”(physical association)	0.560
TCAP	ASB6	psi-mi:“MI:0915”(physical association)	0.560
CHRNB1	ASB6	psi-mi:“MI:0915”(physical association)	0.560
DUSP23	ASB6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (150): ASB6 (Two-hybrid), ASB6 (Two-hybrid), FAM9B (Two-hybrid), ASB6 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), POLR2J (Affinity Capture-MS), POLR2M (Affinity Capture-MS), RNF7 (Affinity Capture-MS), POLR2A (Affinity Capture-MS), E2F6 (Affinity Capture-MS), CORO7 (Affinity Capture-MS), GPN3 (Affinity Capture-MS)

ESM2 similar proteins: A0M8T3, A4D7T3, A6NK59, B2RXR6, P0C927, Q00PJ3, Q07DX6, Q07DY6, Q07E17, Q07E30, Q07E43, Q08DV6, Q09YI3, Q09YJ5, Q09YN0, Q108U1, Q2IBB1, Q2IBB4, Q2IBE3, Q2IBF5, Q2IBG0, Q2QL84, Q2QLA4, Q2QLB5, Q2QLC6, Q2QLH1, Q3SX45, Q3V096, Q5F478, Q5R4M7, Q5ZLC8, Q810B6, Q8BTI7, Q8C6Y6, Q8HXA6, Q8N8A2, Q8N9B4, Q8VD46, Q8VHS6, Q8WMX6

Diamond homologs: A2ARS0, C9JTQ0, L7XCU0, L7XDS4, O00221, O54910, O73630, O75762, O89019, P01125, P01126, P07207, P15307, P15330, P16236, P18954, P19838, P20749, P23631, P25799, P25963, P31695, P51509, P51510, P98149, P98150, P98152, Q00653, Q01201, Q04206, Q04207, Q04861, Q04863, Q04864, Q04865, Q08353, Q2TB02, Q38898, Q3V0J4, Q5I148

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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
Formation of TC-NER Pre-Incision Complex	9	48.8×	3e-11
DNA Damage Recognition in GG-NER	6	43.9×	3e-07
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	5	34.0×	2e-05
Gap-filling DNA repair synthesis and ligation in TC-NER	5	22.9×	1e-04
Dual incision in TC-NER	5	22.2×	1e-04
Neddylation	13	15.8×	8e-11
Signaling by Receptor Tyrosine Kinases	6	8.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	7	94.5×	2e-10
regulation of protein neddylation	5	90.0×	3e-07
protein ubiquitination	9	7.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	86
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
59906	GRCh38/hg38 9q34.11(chr9:127919476-130079974)x3	Pathogenic
59907	GRCh38/hg38 9q34.11(chr9:129036400-130578683)x3	Pathogenic

SpliceAI

1112 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129635203:CCCA:C	acceptor_loss	1.0000
9:129635204:CCA:C	acceptor_loss	1.0000
9:129635205:CA:C	acceptor_loss	1.0000
9:129635206:A:AG	acceptor_gain	1.0000
9:129635206:AG:A	acceptor_gain	1.0000
9:129635207:G:GT	acceptor_gain	1.0000
9:129635207:GG:G	acceptor_gain	1.0000
9:129635207:GGC:G	acceptor_gain	1.0000
9:129635207:GGCC:G	acceptor_gain	1.0000
9:129635207:GGCCA:G	acceptor_gain	1.0000
9:129638455:CCC:C	acceptor_gain	1.0000
9:129638456:CC:C	acceptor_gain	1.0000
9:129638456:CCC:C	acceptor_gain	1.0000
9:129638457:CC:C	acceptor_gain	1.0000
9:129638458:C:CC	acceptor_gain	1.0000
9:129638459:T:G	acceptor_loss	1.0000
9:129638468:C:CT	acceptor_gain	1.0000
9:129638468:C:T	acceptor_gain	1.0000
9:129638574:T:TA	donor_gain	1.0000
9:129639183:T:A	donor_gain	1.0000
9:129639197:CCCA:C	donor_loss	1.0000
9:129639198:CCAC:C	donor_loss	1.0000
9:129639199:CAC:C	donor_loss	1.0000
9:129639200:A:AC	donor_gain	1.0000
9:129639200:A:AT	donor_loss	1.0000
9:129639201:C:CC	donor_gain	1.0000
9:129639201:CCATG:C	donor_gain	1.0000
9:129639310:TC:T	acceptor_loss	1.0000
9:129639311:C:CC	acceptor_gain	1.0000
9:129639311:CTGA:C	acceptor_loss	1.0000

AlphaMissense

2760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129639278:G:C	S145R	0.998
9:129639278:G:T	S145R	0.998
9:129639280:T:G	S145R	0.998
9:129639472:A:T	V111D	0.998
9:129638584:A:G	L196S	0.997
9:129639285:A:G	L143P	0.997
9:129639296:G:C	S139R	0.997
9:129639296:G:T	S139R	0.997
9:129639298:T:G	S139R	0.997
9:129641979:G:C	F7L	0.997
9:129641979:G:T	F7L	0.997
9:129641981:A:G	F7L	0.997
9:129638625:G:C	S182R	0.996
9:129638625:G:T	S182R	0.996
9:129638627:T:G	S182R	0.996
9:129639243:A:G	L157P	0.996
9:129639282:G:T	A144D	0.996
9:129639294:G:C	P140R	0.996
9:129639294:G:T	P140H	0.996
9:129639299:A:C	S138R	0.996
9:129639299:A:T	S138R	0.996
9:129639301:T:G	S138R	0.996
9:129639475:G:T	A110D	0.996
9:129639406:T:A	D133V	0.995
9:129638628:G:C	S181R	0.994
9:129638628:G:T	S181R	0.994
9:129638630:T:G	S181R	0.994
9:129638638:G:T	A178D	0.994
9:129639252:A:G	L154P	0.994
9:129639407:C:G	D133H	0.994

dbSNP variants (sampled 300 via entrez): RS1000035606 (9:129635170 G>A,C,T), RS1000276973 (9:129643970 G>A), RS1000453513 (9:129641772 C>T), RS1000475577 (9:129638833 A>G), RS1000612747 (9:129642760 T>A), RS1000636716 (9:129636227 CAAA>C,CA,CAA,CAAAA,CAAAAA), RS1001070321 (9:129641478 TCCA>T), RS1001217380 (9:129637588 G>A), RS1001318077 (9:129638512 G>A), RS1001621020 (9:129637521 A>G), RS1001628494 (9:129638258 G>A), RS1001689193 (9:129643356 G>A), RS1001823616 (9:129643620 G>A), RS1002024659 (9:129642250 G>A), RS1002160315 (9:129642449 G>T)

Disease associations

OMIM: gene MIM:615051 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
quercitrin	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methotrexate	decreases expression	1
Phenylmercuric Acetate	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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