ASB14

Summary

ASB14 (ankyrin repeat and SOCS box containing 14, HGNC:19766) is a protein-coding gene on chromosome 3p14.3, encoding Ankyrin repeat and SOCS box protein 14 (A6NK59). 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 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. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 142686 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_001142733

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19766
Approved symbol	ASB14
Name	ankyrin repeat and SOCS box containing 14
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp313L0121
Ensembl gene	ENSG00000239388
Ensembl biotype	protein_coding
Entrez	142686

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000487349, ENST00000515033

RefSeq mRNA: 2 — MANE Select: NM_001142733 NM_001142733, NM_130387

CCDS: CCDS46856

Canonical transcript exons

ENST00000487349 — 11 exons

Exon	Start	End
ENSE00001274678	57276528	57276728
ENSE00001632509	57280302	57280473
ENSE00001917874	57268342	57269618
ENSE00002316632	57278377	57278920
ENSE00002326378	57288155	57288286
ENSE00002345196	57287901	57288059
ENSE00002367873	57289068	57289123
ENSE00002376001	57283194	57283439
ENSE00002724329	57291912	57292104
ENSE00003642037	57277767	57277920
ENSE00003894856	57292633	57292685

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 85.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0781 / max 24.4564, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42646	0.0781	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.63	gold quality
muscle of leg	UBERON:0001383	80.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.84	gold quality
gastrocnemius	UBERON:0001388	78.74	gold quality
right uterine tube	UBERON:0001302	76.88	gold quality
apex of heart	UBERON:0002098	71.98	gold quality
heart left ventricle	UBERON:0002084	70.17	gold quality
cardiac ventricle	UBERON:0002082	69.16	gold quality
monocyte	CL:0000576	68.48	gold quality
body of pancreas	UBERON:0001150	68.10	gold quality
leukocyte	CL:0000738	67.56	gold quality
calcaneal tendon	UBERON:0003701	66.47	gold quality
sural nerve	UBERON:0015488	66.37	silver quality
bone marrow cell	CL:0002092	64.96	silver quality
heart	UBERON:0000948	64.50	gold quality
pancreas	UBERON:0001264	64.30	gold quality
tendon	UBERON:0000043	63.41	gold quality
epithelium of nasopharynx	UBERON:0001951	62.60	gold quality
cerebellar cortex	UBERON:0002129	62.25	gold quality
cerebellar hemisphere	UBERON:0002245	62.16	gold quality
adrenal tissue	UBERON:0018303	61.47	gold quality
skin of abdomen	UBERON:0001416	61.37	gold quality
mucosa of stomach	UBERON:0001199	61.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.07	gold quality
granulocyte	CL:0000094	60.98	gold quality
colonic epithelium	UBERON:0000397	60.96	silver quality
skeletal muscle tissue	UBERON:0001134	60.90	gold quality
skin of leg	UBERON:0001511	60.89	gold quality
cerebellum	UBERON:0002037	60.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting ASB14, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb14a	ENSDARG00000008473
danio_rerio	asb14b	ENSDARG00000087741
mus_musculus	Asb14	ENSMUSG00000021898
rattus_norvegicus	Asb14	ENSRNOG00000013346

Paralogs (7): ASB4 (ENSG00000005981), ASB3 (ENSG00000115239), ASB15 (ENSG00000146809), ASB10 (ENSG00000146926), ASB16 (ENSG00000161664), ASB18 (ENSG00000182177), MPHOSPH8 (ENSG00000196199)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 14 — A6NK59 (reviewed: A6NK59)

All UniProt accessions (1): A6NK59

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. Plays a role in the inhibition of cardiomyocyte nuclear proliferation by mediating the ubiquitination and degradation of MAPRE2.

Subunit / interactions. Interacts with MAPRE2; this interaction promotes MAPRE2 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 (3)

UniProt ID	Names	Canonical?
A6NK59-1	1	yes
A6NK59-2	2
A6NK59-3	3

RefSeq proteins (1): NP_001136205* (*=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

Pfam: PF07525, PF12796

UniProt features (18 total): repeat 11, splice variant 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NK59-F1	86.24	0.65

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: 43 (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, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MYOD_Q6, E12_Q6, chr3p14, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_NEDDYLATION, MIR1277_5P, MIR5692B_MIR5692C, MIR664A_3P

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

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

GO Cellular Component (1): 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
intracellular anatomical structure	1
signal transduction	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB14	ANKRD9	Q96BM1	641
ASB14	KLHL21	Q9UJP4	541
ASB14	B7Z1P2	B7Z1P2	499
ASB14	TMEM161A	Q9NX61	478
ASB14	KLHDC1	Q8N7A1	477
ASB14	BTD	P43251	474
ASB14	ARHGEF38	Q9NXL2	410
ASB14	TRIM63	Q969Q1	396
ASB14	A0A096LNH4	A0A096LNH4	393
ASB14	ARFGEF3	Q5TH69	391
ASB14	TSEN54	Q7Z6J9	387
ASB14	SYT15	Q9BQS2	384
ASB14	FBXO32	Q969P5	384
ASB14	KCNH7	Q9NS40	359
ASB14	TTLL1	O95922	349

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ASB14	POTEF	psi-mi:“MI:0915”(physical association)	0.400
ASB14	TOMM40	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): POTEF (Affinity Capture-MS), ASB14 (PCA), POTEF (Affinity Capture-MS), ARHGEF4 (Affinity Capture-MS), SREBF1 (Affinity Capture-MS), DNAJC11 (Affinity Capture-MS), MARCH7 (Affinity Capture-MS), FRMD5 (Affinity Capture-MS), SLC27A3 (Affinity Capture-MS), MFF (Affinity Capture-MS), CDKAL1 (Affinity Capture-MS), TRABD (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), CLCN3 (Affinity Capture-MS), MYO19 (Affinity Capture-MS)

ESM2 similar proteins: A6NK59, A7MB89, B4E2M5, P0C6P7, P0C927, Q08DV6, Q29RM5, Q3SX45, Q3SZE4, Q3UMR0, Q495B1, Q4V890, Q5R5S1, Q5REW9, Q5RFS1, Q5U2S6, Q5ZM55, Q6GPE5, Q7T3P8, Q810B6, Q8C0T1, Q8C6Y6, Q8CEF1, Q8CEL2, Q8HXA6, Q8K0L0, Q8N9B4, Q8VHS6, Q8WXH4, Q8WXK1, Q91ZT8, Q96DX5, Q96JP0, Q96NW4, Q96Q27, Q9BSK4, Q9CQ31, Q9GKW8, Q9H0C1, Q9P2R3

Diamond homologs: A2RUV0, A6NK59, O35516, P0C927, Q04721, Q3SX45, Q58CT0, Q5U2S6, Q8C6Y6, Q8HXA6, Q8K0L0, Q8VHS6, Q8WXK1, Q96Q27, Q9QW30, A2ARS0, C9JTQ0, Q3KP44, Q9W0T5, A2RT91, Q08DV6, Q3V096, Q7Z5J8, Q8N9B4, Q9WV72, Q9WV74, Q9Y575, Q9Y576, Q9P2R3, Q9J519, Q641X1, Q9Z2F6, O73579, Q9CQM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2353 predictions. Top by Δscore:

Variant	Effect	Δscore
3:57277761:ACTT:A	donor_loss	1.0000
3:57277762:CTT:C	donor_loss	1.0000
3:57277763:TTA:T	donor_loss	1.0000
3:57277764:TA:T	donor_loss	1.0000
3:57277765:A:AC	donor_gain	1.0000
3:57277765:A:C	donor_loss	1.0000
3:57277766:C:CA	donor_gain	1.0000
3:57277766:CTTA:C	donor_gain	1.0000
3:57277766:CTTAA:C	donor_gain	1.0000
3:57277916:CAGAA:C	acceptor_gain	1.0000
3:57277918:GAAC:G	acceptor_loss	1.0000
3:57277919:AACTG:A	acceptor_loss	1.0000
3:57277920:ACTGA:A	acceptor_loss	1.0000
3:57277921:C:CC	acceptor_gain	1.0000
3:57277922:T:G	acceptor_loss	1.0000
3:57278372:CTTA:C	donor_loss	1.0000
3:57278373:TTACC:T	donor_loss	1.0000
3:57278374:TACC:T	donor_loss	1.0000
3:57278375:A:AC	donor_gain	1.0000
3:57278376:C:CG	donor_gain	1.0000
3:57278376:CCTTA:C	donor_gain	1.0000
3:57280299:A:AC	donor_gain	1.0000
3:57289120:CAAA:C	acceptor_gain	1.0000
3:57289124:C:CC	acceptor_gain	1.0000
3:57291918:T:TA	donor_gain	1.0000
3:57268395:TAGGA:T	acceptor_gain	0.9900
3:57276729:C:CC	acceptor_gain	0.9900
3:57277766:CT:C	donor_gain	0.9900
3:57277766:CTT:C	donor_gain	0.9900
3:57277787:G:T	donor_gain	0.9900

AlphaMissense

3851 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:57278860:A:C	S316R	0.991
3:57278860:A:T	S316R	0.991
3:57278862:T:G	S316R	0.991
3:57283341:C:G	A191P	0.988
3:57278740:C:A	R356S	0.987
3:57278740:C:G	R356S	0.987
3:57278539:G:C	F423L	0.985
3:57278539:G:T	F423L	0.985
3:57278541:A:G	F423L	0.985
3:57278627:A:G	L394P	0.984
3:57278630:G:T	A393D	0.982
3:57276698:C:G	R539P	0.981
3:57278594:A:G	L405P	0.981
3:57278641:G:C	C389W	0.981
3:57278741:C:G	R356T	0.981
3:57278846:G:T	A321E	0.981
3:57278655:C:G	D385H	0.980
3:57278681:A:G	L376P	0.980
3:57280320:G:T	A290D	0.980
3:57280321:C:G	A290P	0.980
3:57276699:G:T	R539S	0.979
3:57278684:A:G	L375P	0.979
3:57278720:G:T	A363D	0.978
3:57276686:C:G	R543P	0.977
3:57278844:C:G	A322P	0.977
3:57283239:C:G	A225P	0.977
3:57283337:G:T	A192D	0.977
3:57278460:A:G	C450R	0.976
3:57278736:A:G	S358P	0.976
3:57278654:T:G	D385A	0.975

dbSNP variants (sampled 300 via entrez): RS1000311115 (3:57291772 A>C,G), RS1000464361 (3:57285006 C>G), RS1000608787 (3:57285318 CTT>C), RS1000609895 (3:57272686 G>A,C), RS1000642084 (3:57279278 T>A,C), RS1000691471 (3:57279484 A>G), RS1001155255 (3:57285937 G>A), RS1001337621 (3:57273755 A>C,T), RS1001482485 (3:57290558 G>A), RS1001723437 (3:57282798 A>C,G,T), RS1001872068 (3:57273275 A>G), RS1001983470 (3:57294519 C>G,T), RS1002327071 (3:57285517 C>T), RS1002334327 (3:57284209 C>G), RS1002380427 (3:57280081 TATGTCTAAGTACTTTC>T)

Disease associations

OMIM: gene `` | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
incobotulinumtoxinA	decreases expression	1
Doxorubicin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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