ASB12

Summary

ASB12 (ankyrin repeat and SOCS box containing 12, HGNC:19763) is a protein-coding gene on chromosome Xq11.2, encoding Ankyrin repeat and SOCS box protein 12 (Q8WXK4). 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 is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a 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.

Source: NCBI Gene 142689 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_130388

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19763
Approved symbol	ASB12
Name	ankyrin repeat and SOCS box containing 12
Location	Xq11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39577
Ensembl gene	ENSG00000198881
Ensembl biotype	protein_coding
OMIM	300891
Entrez	142689

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000362002

RefSeq mRNA: 1 — MANE Select: NM_130388 NM_130388

CCDS: CCDS14378

Canonical transcript exons

ENST00000362002 — 3 exons

Exon	Start	End
ENSE00001268509	64230463	64230607
ENSE00001268519	64224194	64224468
ENSE00003658825	64224828	64225674

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 97.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1208 / max 36.6846, expressed in 24 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199477	0.1208	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.71	gold quality
vastus lateralis	UBERON:0001379	96.05	gold quality
quadriceps femoris	UBERON:0001377	95.95	gold quality
biceps brachii	UBERON:0001507	94.68	gold quality
kidney epithelium	UBERON:0004819	94.26	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.86	gold quality
deltoid	UBERON:0001476	93.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.73	gold quality
left ventricle myocardium	UBERON:0006566	93.66	silver quality
sperm	CL:0000019	93.38	gold quality
gastrocnemius	UBERON:0001388	93.29	gold quality
skeletal muscle tissue	UBERON:0001134	93.25	gold quality
superficial temporal artery	UBERON:0001614	93.12	silver quality
cardiac muscle of right atrium	UBERON:0003379	92.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.44	silver quality
muscle of leg	UBERON:0001383	92.02	gold quality
tibialis anterior	UBERON:0001385	91.79	silver quality
muscle tissue	UBERON:0002385	90.01	gold quality
body of tongue	UBERON:0011876	88.15	gold quality
tongue	UBERON:0001723	85.98	gold quality
gingival epithelium	UBERON:0001949	85.71	silver quality
lower lobe of lung	UBERON:0008949	85.24	silver quality
nasal cavity epithelium	UBERON:0005384	82.96	gold quality
cerebellar vermis	UBERON:0004720	82.03	gold quality
superior surface of tongue	UBERON:0007371	81.74	gold quality
epithelial cell of pancreas	CL:0000083	81.22	gold quality
germinal epithelium of ovary	UBERON:0001304	80.22	silver quality
upper arm skin	UBERON:0004263	79.64	gold quality
vena cava	UBERON:0004087	79.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting ASB12, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-7847-3P	96.63	64.58	952

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb12a	ENSDARG00000017086
danio_rerio	asb12b	ENSDARG00000037558
mus_musculus	Asb12	ENSMUSG00000031204
rattus_norvegicus	Asb12	ENSRNOG00000004197

Paralogs (1): ANKRD29 (ENSG00000154065)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 12 — Q8WXK4 (reviewed: Q8WXK4)

All UniProt accessions (1): Q8WXK4

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.

Subunit / interactions. Interacts with CUL5 and RNF7.

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?
Q8WXK4-1	1	yes
Q8WXK4-2	2

RefSeq proteins (1): NP_569059* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001496	SOCS_box	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051573	Ankyrin-SOCS_box_domain	Family

Pfam: PF07525, PF12796

UniProt features (9 total): repeat 5, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXK4-F1	83.26	0.45

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: 45 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MODULE_48, MODULE_95, GOCC_TRANSFERASE_COMPLEX, CAMPS_COLON_CANCER_COPY_NUMBER_DN, GOMF_ACYLTRANSFERASE_ACTIVITY, GOCC_UBIQUITIN_LIGASE_COMPLEX, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, chrXq11

GO Biological Process (1): protein ubiquitination (GO:0016567)

GO Molecular Function (2): protein binding (GO:0005515), ubiquitin protein ligase activity (GO:0061630)

GO Cellular Component (2): ubiquitin ligase complex (GO:0000151), cytosol (GO:0005829)

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
protein modification by small protein conjugation	1
binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
intracellular protein-containing complex	1
transferase complex	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB12	CUL5	Q93034	567
ASB12	PWWP2B	Q6NUJ5	549
ASB12	LRRC30	A6NM36	539
ASB12	LRRC14B	A6NHZ5	527
ASB12	LRRC20	Q8TCA0	523
ASB12	RBM12	Q9NTZ6	518
ASB12	RNF7	Q9UBF6	493
ASB12	ZDHHC15	Q96MV8	488
ASB12	TMPRSS9	Q7Z410	475
ASB12	ATP8B2	P98198	458
ASB12	WDR88	Q6ZMY6	454
ASB12	GPR101	Q96P66	447
ASB12	OR6C2	Q9NZP2	441
ASB12	LRRC38	Q5VT99	436
ASB12	PCMTD2	Q9NV79	435

IntAct

6 interactions, top by confidence:

A	B	Type	Score
rep	ASB12	psi-mi:“MI:0915”(physical association)	0.490
RNF7	ASB12	psi-mi:“MI:0915”(physical association)	0.400
CUL5	ASB12	psi-mi:“MI:0915”(physical association)	0.400
LZTR1	ASB12	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (36): ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), ASB12 (Two-hybrid), CUL5 (Affinity Capture-Western), RNF7 (Affinity Capture-Western), ASB12 (Two-hybrid), PFN1 (Affinity Capture-MS), PFN2 (Affinity Capture-MS), ACTB (Affinity Capture-MS), TCEB1 (Affinity Capture-MS)

ESM2 similar proteins: A2ASA8, A5PJJ5, A6NE52, A6NHZ5, B6CZ46, E9QAM5, G7PWZ3, P08571, P10810, P33076, P52824, P79621, P86243, Q15048, Q15345, Q1L8H0, Q28680, Q32PG9, Q3U1Y4, Q3UJB3, Q3UWY1, Q3V1N1, Q3V3V9, Q3ZBI5, Q569B5, Q5BK65, Q5DU56, Q5M936, Q63035, Q63691, Q640Z9, Q66H52, Q68EF8, Q6F5E8, Q6GPH6, Q6P5E8, Q6QNU9, Q6R5P0, Q7RTR2, Q80VA5

Diamond homologs: Q8WXK4, Q9D738, Q9WV74, Q9Y576, Q17QS6, Q5M877, Q6ZVZ8, Q862Z2, Q8K0L0, Q8VHA6, Q8VHS5, Q8WWX0, Q96DX5, Q96NS5, Q99619, Q9CQ31, Q9D5L7, Q3SX45, Q91ZT8, Q96Q27, Q9D1A4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

553 predictions. Top by Δscore:

Variant	Effect	Δscore
X:64225670:CAGAT:C	acceptor_gain	0.9900
X:64225673:ATC:A	acceptor_loss	0.9900
X:64225674:TCT:T	acceptor_loss	0.9900
X:64225675:C:CC	acceptor_gain	0.9900
X:64225676:T:G	acceptor_loss	0.9900
X:64225671:AGAT:A	acceptor_gain	0.9800
X:64225672:GAT:G	acceptor_gain	0.9800
X:64225681:G:GC	acceptor_gain	0.9800
X:64228444:TTC:T	donor_gain	0.9800
X:64228445:TCT:T	donor_gain	0.9800
X:64225673:AT:A	acceptor_gain	0.9600
X:64225681:G:C	acceptor_gain	0.9600
X:64230462:CCGGG:C	donor_gain	0.9600
X:64225582:C:CC	acceptor_gain	0.9500
X:64230454:GGTAC:G	donor_loss	0.9500
X:64230455:GTAC:G	donor_loss	0.9500
X:64230456:TACT:T	donor_loss	0.9500
X:64230457:AC:A	donor_loss	0.9500
X:64230458:CTC:C	donor_loss	0.9500
X:64230459:T:TA	donor_loss	0.9500
X:64230460:CACC:C	donor_loss	0.9500
X:64230461:A:AT	donor_loss	0.9500
X:64230461:A:AC	donor_gain	0.9400
X:64230462:C:CC	donor_gain	0.9400
X:64225690:A:T	acceptor_gain	0.9300
X:64224469:C:CC	acceptor_gain	0.9000
X:64225685:C:CT	acceptor_gain	0.9000
X:64225689:C:CT	acceptor_gain	0.9000
X:64230402:CAGGT:C	donor_gain	0.9000
X:64225677:G:C	acceptor_gain	0.8800

AlphaMissense

2058 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000341377 (X:64230631 T>A), RS1000691889 (X:64230305 C>T), RS1001027259 (X:64228446 C>T), RS1001396249 (X:64228097 A>G), RS1001499945 (X:64225828 C>T), RS1001526162 (X:64231184 T>C), RS1001634331 (X:64223725 G>A), RS1002993447 (X:64231369 C>G), RS1003112614 (X:64224160 G>A,T), RS1003576016 (X:64224439 G>A), RS1003955095 (X:64224076 G>A), RS1004434350 (X:64230386 G>A,C), RS1004908945 (X:64230674 C>T), RS1004909574 (X:64225094 T>C,G), RS1004924827 (X:64225730 T>C)

Disease associations

OMIM: gene MIM:300891 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, affects methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, affects methylation	1
Benzo(a)pyrene	increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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