ASB5

Summary

ASB5 (ankyrin repeat and SOCS box containing 5, HGNC:17180) is a protein-coding gene on chromosome 4q34.2, encoding Ankyrin repeat and SOCS box protein 5 (Q8WWX0). 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.

The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene but their full length sequences are not known.

Source: NCBI Gene 140458 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_080874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17180
Approved symbol	ASB5
Name	ankyrin repeat and SOCS box containing 5
Location	4q34.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164122
Ensembl biotype	protein_coding
OMIM	615050
Entrez	140458

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000296525, ENST00000505299, ENST00000510578, ENST00000511879, ENST00000512254, ENST00000672074, ENST00000855722, ENST00000855723, ENST00000855724, ENST00000945694, ENST00000945695, ENST00000945696

RefSeq mRNA: 2 — MANE Select: NM_080874 NM_001410863, NM_080874

CCDS: CCDS3827, CCDS93672

Canonical transcript exons

ENST00000296525 — 7 exons

Exon	Start	End
ENSE00001081665	176221450	176221600
ENSE00001081666	176221155	176221289
ENSE00001081670	176268913	176269222
ENSE00001254223	176216818	176217009
ENSE00001254259	176213673	176215727
ENSE00003502184	176222313	176222420
ENSE00003603238	176225262	176225341

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 99.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.8289 / max 1128.4699, expressed in 162 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55032	5.9475	148
55030	0.4764	98
55031	0.3030	89
55029	0.0579	28
55033	0.0196	10
55034	0.0176	5
55028	0.0069	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.54	gold quality
deltoid	UBERON:0001476	99.33	gold quality
quadriceps femoris	UBERON:0001377	99.31	gold quality
tibialis anterior	UBERON:0001385	99.31	gold quality
vastus lateralis	UBERON:0001379	99.29	gold quality
biceps brachii	UBERON:0001507	99.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.08	gold quality
skeletal muscle tissue	UBERON:0001134	98.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.87	gold quality
body of tongue	UBERON:0011876	97.56	gold quality
gastrocnemius	UBERON:0001388	97.15	gold quality
skeletal muscle organ	UBERON:0014892	95.94	gold quality
muscle of leg	UBERON:0001383	95.10	gold quality
muscle tissue	UBERON:0002385	90.74	gold quality
tongue	UBERON:0001723	90.65	gold quality
parotid gland	UBERON:0001831	89.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.13	gold quality
lower esophagus	UBERON:0013473	80.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.92	gold quality
superior surface of tongue	UBERON:0007371	79.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.85	gold quality
mucosa of stomach	UBERON:0001199	78.82	gold quality
urethra	UBERON:0000057	74.06	gold quality
pharyngeal mucosa	UBERON:0000355	73.81	gold quality
urinary bladder	UBERON:0001255	72.80	gold quality
prostate gland	UBERON:0002367	71.31	gold quality
left testis	UBERON:0004533	69.26	gold quality
right testis	UBERON:0004534	68.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.99

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asb5	ENSMUSG00000031519
rattus_norvegicus	Asb5	ENSRNOG00000042630

Paralogs (2): ASB9 (ENSG00000102048), ASB11 (ENSG00000165192)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 5 — Q8WWX0 (reviewed: Q8WWX0)

All UniProt accessions (4): A0A5F9ZHS2, Q8WWX0, D6R9Q2, Q5HYF3

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. May play a role in the initiation of arteriogenesis.

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?
Q8WWX0-1	1	yes
Q8WWX0-2	2

RefSeq proteins (2): NP_001397792, NP_543150* (*=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
IPR037328	ASB5_SOCS	Domain
IPR051573	Ankyrin-SOCS_box_domain	Family

Pfam: PF07525, PF12796

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-Q8WWX0-F1	85.93	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: 101 (showing top): AP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr4q34, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, AP4_Q6, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, MODULE_285, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, TGANTCA_AP1_C

GO Biological Process (3): protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556), positive regulation of protein catabolic process (GO:0045732)

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

GO Cellular Component (2): cytosol (GO:0005829), membrane (GO:0016020)

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
cellular anatomical structure	2
protein modification by small protein conjugation	1
intracellular anatomical structure	1
signal transduction	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

1535 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB5	SPCS3	P12280	588
ASB5	WDR17	Q8IZU2	538
ASB5	IRAG1	Q9Y6F6	527
ASB5	PTPRD	P23468	521
ASB5	SPATA4	Q8NEY3	520
ASB5	NEURL2	Q9BR09	487
ASB5	PNMA1	Q8ND90	460
ASB5	CTXND1	A0A1B0GTU2	437
ASB5	ASB6	Q9NWX5	432
ASB5	CARD19	Q96LW7	431
ASB5	LRRC30	A6NM36	429
ASB5	FBXO7	Q9Y3I1	424
ASB5	ABTB1	Q969K4	412
ASB5	CUEDC1	Q9NWM3	411
ASB5	ASIC2	Q16515	410

IntAct

0 interactions, top by confidence:

BioGRID (23): ASB5 (PCA), CUL5 (Affinity Capture-MS), TCEB2 (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), SLIRP (Affinity Capture-MS), ASB1 (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), PRKDC (Affinity Capture-MS), CRYAB (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP2A2 (Affinity Capture-MS), BSG (Affinity Capture-MS), RPN1 (Affinity Capture-MS), RAB1A (Affinity Capture-MS)

ESM2 similar proteins: A0MQH0, A4II29, A4IIX9, E9PTA2, O94826, P24786, Q0VC93, Q13507, Q16288, Q17QS6, Q25BN1, Q3ULA2, Q502M6, Q59H18, Q5GIG6, Q5IFJ9, Q5IS37, Q5IS82, Q5U5A6, Q5ZLX4, Q6DFV5, Q6GPR5, Q6GQW0, Q6TUI4, Q75Q39, Q7T3X9, Q7T3Y0, Q7TQP6, Q7Z6K4, Q7Z713, Q862Z2, Q8BPU7, Q8K4Q0, Q8N122, Q8VBX0, Q8WWX0, Q8WXK3, Q91987, Q91YD4, Q91ZA8

Diamond homologs: G0LXV8, L7X8P2, L7XCU0, L7XDS4, P0DJE3, P0DJE5, P23631, Q02989, Q09701, Q17QS6, Q21209, Q25338, Q5EA33, Q755Y0, Q862Z2, Q8WVL7, Q8WWX0, Q9D1A4, Q9XZC0, Q3SZE4, Q5RFS1, Q70X92, Q810B6, Q8VBX0, Q8WXH4, Q8WXK3, Q91ZT8, Q91ZU0, Q96DX5, Q9BSK4, Q9CQ31, Q9J4Z6, Q9WV74, Q9Y576, B4E2M5, D3J162, D3J163, O83515, Q14161, Q3SX00

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

852 predictions. Top by Δscore:

Variant	Effect	Δscore
4:176217010:C:CC	acceptor_gain	1.0000
4:176217022:C:CT	acceptor_gain	1.0000
4:176221170:T:TA	donor_gain	1.0000
4:176221445:GTTAC:G	donor_loss	1.0000
4:176221446:TTA:T	donor_loss	1.0000
4:176221447:TACCT:T	donor_loss	1.0000
4:176221448:ACCTT:A	donor_loss	1.0000
4:176221449:C:CT	donor_loss	1.0000
4:176221596:TTTAC:T	acceptor_gain	1.0000
4:176221612:C:CT	acceptor_gain	1.0000
4:176225258:TTA:T	donor_loss	1.0000
4:176225259:TACCT:T	donor_loss	1.0000
4:176225260:ACC:A	donor_loss	1.0000
4:176225261:C:CG	donor_loss	1.0000
4:176225339:AACC:A	acceptor_loss	1.0000
4:176225342:C:CC	acceptor_gain	1.0000
4:176225342:CT:C	acceptor_loss	1.0000
4:176225343:T:C	acceptor_loss	1.0000
4:176225346:C:CT	acceptor_gain	1.0000
4:176268908:CATA:C	donor_loss	1.0000
4:176268909:ATACC:A	donor_loss	1.0000
4:176268910:TA:T	donor_loss	1.0000
4:176268912:C:CT	donor_loss	1.0000
4:176215725:TAG:T	acceptor_gain	0.9900
4:176215728:C:CC	acceptor_gain	0.9900
4:176216812:TCTTA:T	donor_loss	0.9900
4:176216813:CTTA:C	donor_loss	0.9900
4:176216814:TTA:T	donor_loss	0.9900
4:176216815:TACCT:T	donor_loss	0.9900
4:176216816:A:C	donor_loss	0.9900

AlphaMissense

2123 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:176269007:G:C	S34R	0.999
4:176269007:G:T	S34R	0.999
4:176269009:T:G	S34R	0.999
4:176222369:C:G	A110P	0.998
4:176222332:A:G	L122P	0.997
4:176222364:G:C	C111W	0.997
4:176222366:A:G	C111R	0.997
4:176225305:G:T	A78E	0.997
4:176269033:A:G	C26R	0.997
4:176221555:A:G	C144R	0.996
4:176221558:C:G	A143P	0.996
4:176225306:C:G	A78P	0.996
4:176221569:G:C	P139R	0.995
4:176225309:C:G	A77P	0.995
4:176269005:A:G	L35P	0.995
4:176221462:C:G	A175P	0.994
4:176222377:A:C	L107W	0.994
4:176222377:A:G	L107S	0.994
4:176268958:C:G	A51P	0.994
4:176269023:A:G	L29P	0.994
4:176269025:C:A	K28N	0.994
4:176269025:C:G	K28N	0.994
4:176222341:G:T	A119D	0.993
4:176222343:A:C	C118W	0.993
4:176222365:C:T	C111Y	0.993
4:176222380:G:C	P106R	0.993
4:176269047:A:T	I21K	0.993
4:176216874:G:T	P269H	0.992
4:176221521:A:G	L155P	0.992
4:176221553:G:C	C144W	0.992

dbSNP variants (sampled 300 via entrez): RS1000008694 (4:176217175 C>T), RS1000041021 (4:176245902 G>T), RS1000062312 (4:176220018 C>T), RS1000088838 (4:176252317 A>G), RS1000119398 (4:176240482 G>A), RS1000141259 (4:176252097 A>G), RS1000176792 (4:176275022 C>T), RS1000181795 (4:176224842 A>G), RS1000229156 (4:176274660 C>T), RS1000236770 (4:176254581 C>G), RS1000305084 (4:176231954 G>T), RS1000327091 (4:176258448 A>G), RS10003543 (4:176214469 G>A), RS1000365629 (4:176231302 C>G,T), RS1000379737 (4:176237693 A>G)

Disease associations

OMIM: gene MIM:615050 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_388	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010437	triacylglycerol 58:10 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
2-methyl-4-isothiazolin-3-one	increases expression	1
CGP 52608	increases reaction, affects binding	1
Arsenic Trioxide	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Smoke	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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