ASB10

Summary

ASB10 (ankyrin repeat and SOCS box containing 10, HGNC:17185) is a protein-coding gene on chromosome 7q36.1, encoding Ankyrin repeat and SOCS box protein 10 (Q8WXI3). 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. The SOCS box serves to couple suppressor of cytokine signaling (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.

Source: NCBI Gene 136371 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obsolete glaucoma 1, open angle, F (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 209 total
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001142459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17185
Approved symbol	ASB10
Name	ankyrin repeat and SOCS box containing 10
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000146926
Ensembl biotype	protein_coding
OMIM	615054
Entrez	136371

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000275838, ENST00000377867, ENST00000415615, ENST00000420175, ENST00000968508, ENST00000968509

RefSeq mRNA: 3 — MANE Select: NM_001142459 NM_001142459, NM_001142460, NM_080871

CCDS: CCDS47749, CCDS47750, CCDS5921

Canonical transcript exons

ENST00000420175 — 6 exons

Exon	Start	End
ENSE00000978047	151180939	151181458
ENSE00001140229	151186392	151186659
ENSE00001211902	151175698	151175966
ENSE00001475355	151176563	151176676
ENSE00001682627	151186815	151187250
ENSE00002218244	151176112	151176297

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 94.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1566 / max 31.2498, expressed in 31 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86880	0.0605	22
86881	0.0443	23
86878	0.0356	17
86879	0.0162	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.90	gold quality
apex of heart	UBERON:0002098	93.39	gold quality
gastrocnemius	UBERON:0001388	90.97	gold quality
muscle of leg	UBERON:0001383	89.42	gold quality
heart left ventricle	UBERON:0002084	84.97	gold quality
cardiac ventricle	UBERON:0002082	84.03	gold quality
skeletal muscle tissue	UBERON:0001134	81.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.48	silver quality
quadriceps femoris	UBERON:0001377	78.94	silver quality
vastus lateralis	UBERON:0001379	78.71	silver quality
right atrium auricular region	UBERON:0006631	77.91	gold quality
cardiac atrium	UBERON:0002081	77.32	gold quality
heart	UBERON:0000948	76.48	gold quality
biceps brachii	UBERON:0001507	75.51	silver quality
muscle tissue	UBERON:0002385	75.08	gold quality
buccal mucosa cell	CL:0002336	73.38	gold quality
deltoid	UBERON:0001476	68.50	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	66.36	silver quality
body of tongue	UBERON:0011876	61.87	gold quality
tendon of biceps brachii	UBERON:0008188	59.47	gold quality
myocardium	UBERON:0002349	57.68	gold quality
tongue	UBERON:0001723	57.45	gold quality
heart right ventricle	UBERON:0002080	56.07	gold quality
oviduct epithelium	UBERON:0004804	55.86	gold quality
parotid gland	UBERON:0001831	54.85	gold quality
right coronary artery	UBERON:0001625	54.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.68	silver quality
medial globus pallidus	UBERON:0002477	50.52	gold quality
left coronary artery	UBERON:0001626	49.55	gold quality
coronary artery	UBERON:0001621	49.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting ASB10, 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-4671-3P	99.88	72.46	1045
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-631	97.05	66.93	602

Literature-anchored findings (GeneRIF, showing 6)

• These findings suggested that the genes in the GLC1F locus may be associated with the pathogenesis of normal tension glaucoma. (PMID:20309402)
• Variants in ASB10 are associated with open-angle glaucoma. (PMID:22156576)
• non-synonymous mutations in ASB10 do not cause Mendelian forms of primary open angle glaucoma (PMID:22798626)
• ASB10 may play a role in ubiquitin-mediated degradation pathways in tabecular meshwork cells. (PMID:23901248)
• Variants in ASB10 were found to be significantly associated with sporadic POAG in the Pakistani population (PMID:26713451)
• Lack of Correlation between ASB10 and Normal-tension Glaucoma in a Population from the Republic of Korea. (PMID:31522561)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb10	ENSDARG00000099461
mus_musculus	Asb10	ENSMUSG00000038204
rattus_norvegicus	Asb10	ENSRNOG00000024885

Paralogs (7): ASB4 (ENSG00000005981), ASB3 (ENSG00000115239), ASB15 (ENSG00000146809), ASB16 (ENSG00000161664), ASB18 (ENSG00000182177), MPHOSPH8 (ENSG00000196199), ASB14 (ENSG00000239388)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 10 — Q8WXI3 (reviewed: Q8WXI3)

All UniProt accessions (3): Q8WXI3, A0A090N8I2, F8WB38

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.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in the eye. The highest expression is observed in the iris, with moderate levels in the trabecular meshwork (TM), the lamina, and the optic nerve; slightly lower levels in the ciliary body, retina, and choroid; and very low levels in the lens.

Disease relevance. Glaucoma 1, open angle, F (GLC1F) [MIM:603383] A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. The disease is caused by variants affecting the gene represented in this entry.

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?
Q8WXI3-1	1	yes
Q8WXI3-2	2
Q8WXI3-3	3

RefSeq proteins (3): NP_001135931, NP_001135932, NP_543147 (=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
IPR050663	Ankyrin-SOCS_Box	Family

Pfam: PF00023, PF07525, PF12796

UniProt features (42 total): sequence variant 29, repeat 7, splice variant 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXI3-F1	78.98	0.40

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: 31 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MARTENS_TRETINOIN_RESPONSE_UP, FIGUEROA_AML_METHYLATION_CLUSTER_1_DN, FIGUEROA_AML_METHYLATION_CLUSTER_3_DN, REACTOME_NEDDYLATION, MIR4254, GSE13485_DAY1_VS_DAY3_YF17D_VACCINE_PBMC_UP, GSE13485_DAY1_VS_DAY7_YF17D_VACCINE_PBMC_UP, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_CONJUGATION, HP_GLAUCOMA, HP_VISUAL_IMPAIRMENT

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

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

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), 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
intracellular anatomical structure	2
cellular anatomical structure	2
protein modification by small protein conjugation	1
signal transduction	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB10	WDR36	Q8NI36	906
ASB10	MYOC	Q99972	857
ASB10	OPTN	Q96CV9	761
ASB10	NTF4	P34130	720
ASB10	CYP1B1	Q16678	704
ASB10	Q4G0F9	Q4G0F9	618
ASB10	LMX1B	O60663	587
ASB10	SRBD1	Q8N5C6	573
ASB10	LTBP2	Q14767	536
ASB10	CUL5	Q93034	522
ASB10	ANKRD9	Q96BM1	519
ASB10	EFNA5	P52803	507
ASB10	TMCO1	Q9UM00	495
ASB10	DRC11L	A6NCM1	480
ASB10	FOXC1	Q12948	409

IntAct

12 interactions, top by confidence:

A	B	Type	Score
MEOX2	ASB10	psi-mi:“MI:0915”(physical association)	0.560
LCN2	ASB10	psi-mi:“MI:0915”(physical association)	0.560
ASB10	MRPL23	psi-mi:“MI:0915”(physical association)	0.370
ARFGAP1	ASB10	psi-mi:“MI:0915”(physical association)	0.370
ASB10	AGR3	psi-mi:“MI:0915”(physical association)	0.370
KDM1A	ASB10	psi-mi:“MI:0915”(physical association)	0.370
ASB10	THAP12	psi-mi:“MI:0914”(association)	0.350
ASB10	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
ASB10	LCN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): HIF1AN (Affinity Capture-MS), PRKRIR (Affinity Capture-MS), ASB10 (Two-hybrid), LCN2 (Two-hybrid), HIF1AN (Affinity Capture-MS), POLD2 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), PRKRIR (Affinity Capture-MS), ASB10 (Two-hybrid), PSMA4 (Affinity Capture-Western), HSPA1A (Affinity Capture-Western), ASB10 (Two-hybrid), ASB10 (Two-hybrid), MRPL23 (Two-hybrid), KDM1A (Two-hybrid)

ESM2 similar proteins: A1A4I4, A5PKD8, A6NED2, A8MQ27, O35465, O60294, O75808, O94819, O95382, P70268, Q0MW30, Q14318, Q16512, Q2T9J0, Q32NY4, Q32P44, Q3B7U9, Q3MHW0, Q3U5Q7, Q3USL1, Q4R828, Q561R2, Q5EBM0, Q5EBP3, Q5PQP9, Q60806, Q63433, Q6PAT0, Q7T0L4, Q8BNW9, Q8BTU7, Q8BYR1, Q8IYL2, Q8N5A5, Q8NEP7, Q8VC03, Q8VHS5, Q8WXI3, Q91ZT7, Q96C12

Diamond homologs: A0A0R4IQZ2, Q6ZVZ8, Q8VHA6, Q8VHS5, Q8WXI3, Q91ZT7, Q96NS5, Q9WV71, Q9Y574, Q17QS6, Q862Z2, Q8WWX0, Q9D1A4, Q9WV74, Q9Y576, O35516, Q04721, Q2T9W8, Q3KP44, Q8BLD6, Q9QW30, A6NGH8, Q04749, Q21209, Q4JHE0, Q5RFS1, Q641X1, Q86WC6, Q8UVC1, Q8WXH4, Q9CQ31, Q9D119, Q9FY48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	30
Benign	40

Top pathogenic / likely-pathogenic (0)

SpliceAI

554 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151176557:TCTGA:T	donor_loss	1.0000
7:151176558:CTGA:C	donor_loss	1.0000
7:151176559:TGACC:T	donor_loss	1.0000
7:151176560:GA:G	donor_loss	1.0000
7:151176561:A:T	donor_loss	1.0000
7:151176562:CCTGC:C	donor_loss	1.0000
7:151176673:GCACC:G	acceptor_loss	1.0000
7:151176674:CAC:C	acceptor_gain	1.0000
7:151176675:ACCT:A	acceptor_loss	1.0000
7:151176676:CCTGT:C	acceptor_loss	1.0000
7:151176678:T:A	acceptor_loss	1.0000
7:151186390:A:AC	donor_gain	1.0000
7:151186391:C:CC	donor_gain	1.0000
7:151186391:CT:C	donor_gain	1.0000
7:151186437:T:TA	donor_gain	1.0000
7:151186813:A:AC	donor_gain	1.0000
7:151186814:C:CC	donor_gain	1.0000
7:151186814:CT:C	donor_gain	1.0000
7:151186817:A:AC	donor_gain	1.0000
7:151186817:AGAG:A	donor_gain	1.0000
7:151186818:G:C	donor_gain	1.0000
7:151186845:T:TA	donor_gain	1.0000
7:151175964:CAT:C	acceptor_gain	0.9900
7:151176293:TGTTT:T	acceptor_gain	0.9900
7:151176296:TT:T	acceptor_gain	0.9900
7:151176296:TTCTG:T	acceptor_loss	0.9900
7:151176298:C:CC	acceptor_gain	0.9900
7:151176298:C:CG	acceptor_loss	0.9900
7:151176299:T:A	acceptor_loss	0.9900
7:151176579:G:C	donor_gain	0.9900

AlphaMissense

2964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:151180959:A:G	W362R	0.984
7:151180959:A:T	W362R	0.984
7:151180957:C:A	W362C	0.983
7:151180957:C:G	W362C	0.983
7:151186870:A:C	F87L	0.979
7:151186870:A:T	F87L	0.979
7:151186872:A:G	F87L	0.979
7:151186605:G:T	A124D	0.977
7:151176664:A:G	W373R	0.976
7:151176664:A:T	W373R	0.976
7:151186654:A:G	W108R	0.974
7:151186654:A:T	W108R	0.974
7:151186846:C:A	W95C	0.973
7:151186846:C:G	W95C	0.973
7:151181434:A:C	F203L	0.972
7:151181434:A:T	F203L	0.972
7:151181436:A:G	F203L	0.972
7:151186652:C:A	W108C	0.972
7:151186652:C:G	W108C	0.972
7:151186871:A:G	F87S	0.971
7:151186524:G:T	A151D	0.970
7:151186848:A:G	W95R	0.970
7:151186848:A:T	W95R	0.970
7:151186608:G:T	A123E	0.967
7:151186620:G:T	P119Q	0.967
7:151186606:C:G	A124P	0.966
7:151186620:G:C	P119R	0.965
7:151181137:G:C	C302W	0.964
7:151180994:A:T	V350D	0.963
7:151186954:C:A	W59C	0.961

dbSNP variants (sampled 300 via entrez): RS1000040994 (7:151181055 G>A,C,T), RS1000596153 (7:151185505 A>C), RS1001162619 (7:151180148 C>T), RS1001220258 (7:151187000 C>T), RS1001391104 (7:151183129 A>G), RS1001431742 (7:151176772 A>G), RS1001648551 (7:151184052 G>T), RS1001809015 (7:151188661 T>A), RS1002108216 (7:151178924 C>A), RS1002864231 (7:151180856 A>G), RS1002895824 (7:151186099 C>T), RS1003006438 (7:151183196 A>G), RS1003106585 (7:151177974 G>A), RS1003155124 (7:151175580 G>A), RS1003158783 (7:151177630 C>G)

Disease associations

OMIM: gene MIM:615054 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
glaucoma 1, open angle, F	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
obsolete glaucoma 1, open angle, F	Limited	AD

Mondo (1): (MONDO:0011311)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0007854	Glaucomatous visual field defect
HP:0007906	Ocular hypertension
HP:0012108	Open angle glaucoma
HP:0012796	Increased cup-to-disc ratio

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003476_9	Eyebrow thickness	7.000000e-06
GCST010276_10	Renal underexcretion gout	8.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566383	Glaucoma 1, Open Angle, F (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Phthalic Acids	increases methylation	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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