ASB8

Summary

ASB8 (ankyrin repeat and SOCS box containing 8, HGNC:17183) is a protein-coding gene on chromosome 12q13.11, encoding Ankyrin repeat and SOCS box protein 8 (Q9H765). 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.

Predicted to be involved in intracellular signal transduction and protein ubiquitination. Predicted to be located in cytosol.

Source: NCBI Gene 140461 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 46 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 23 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.00 (unconstrained)
• MANE Select transcript: NM_024095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17183
Approved symbol	ASB8
Name	ankyrin repeat and SOCS box containing 8
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC5540, FLJ21255
Ensembl gene	ENSG00000177981
Ensembl biotype	protein_coding
OMIM	615053
Entrez	140461

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 23 protein_coding, 6 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000317697

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 5, TSL 3: 3, TSL 4: 4, TSL 5: 4

ENST00000317697, ENST00000535055, ENST00000535988, ENST00000536071, ENST00000536549, ENST00000536938, ENST00000536953, ENST00000537754, ENST00000539464, ENST00000539503, ENST00000539528, ENST00000539865, ENST00000540143, ENST00000540212, ENST00000540782, ENST00000545791, ENST00000548228, ENST00000629941, ENST00000873811, ENST00000873812, ENST00000938966, ENST00000938967, ENST00000942522, ENST00000942523, ENST00000995283, ENST00001016621, ENST00001016622, ENST00001016623, ENST00001016624, ENST00001092541, ENST00001137257

RefSeq mRNA: 7 — MANE Select: NM_024095 NM_001319296, NM_001319297, NM_001319298, NM_001319299, NM_001319300, NM_001319301, NM_024095

CCDS: CCDS81686, CCDS8761

Canonical transcript exons

ENST00000317697 — 4 exons

Exon	Start	End
ENSE00001218337	48153368	48153529
ENSE00002222871	48157459	48157515
ENSE00002228904	48147789	48149998
ENSE00003636880	48151201	48151305

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1043 / max 153.3998, expressed in 1802 samples.

Highest expression (Bgee): gastrocnemius, hindlimb stylopod muscle, muscle of leg, skeletal muscle tissue of rectus abdominis, muscle organ.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASB8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 23 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 60 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Frontal Cortex BA9	eqtl	1.0e-24	+0.58	12:48070692:A:G
Muscle Skeletal	sqtl	6.7e-24	-0.65	12:48168521:C:T
Brain Caudate basal ganglia	eqtl	1.8e-22	+0.52	12:48132078:A:G
Brain Cortex	eqtl	7.3e-20	+0.56	12:48108791:G:A
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-17	+0.55	12:48125722:T:G
Brain Cerebellar Hemisphere	eqtl	4.8e-15	+0.49	12:48032609:T:G
Testis	eqtl	5.0e-15	+0.35	12:48108317:A:G
Brain Spinal cord cervical c-1	eqtl	6.3e-15	+0.66	12:48108791:G:A
Brain Putamen basal ganglia	eqtl	7.5e-15	+0.53	12:48122681:G:T
Brain Hippocampus	eqtl	1.3e-14	+0.49	12:48108317:A:G
Brain Hypothalamus	eqtl	4.6e-14	+0.48	12:48125722:T:G
Brain Anterior cingulate cortex BA24	eqtl	7.3e-14	+0.49	12:48124481:A:C
Brain Frontal Cortex BA9	sqtl	5.0e-13	-0.80	12:48159203:CT:C
Nerve Tibial	eqtl	8.9e-12	+0.25	12:48125722:T:G
Brain Cerebellum	eqtl	4.0e-11	+0.44	12:48032609:T:G
Brain Cortex	sqtl	1.8e-09	-0.78	12:48179259:GGT:G
Brain Substantia nigra	eqtl	9.7e-09	+0.44	12:48122681:G:T
Heart Atrial Appendage	eqtl	8.3e-08	+0.15	12:48124481:A:C
Heart Left Ventricle	eqtl	8.6e-08	+0.14	12:48124481:A:C
Adipose Subcutaneous	eqtl	1.2e-07	+0.19	12:48124481:A:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130727	17.3111	1798
130728	1.7543	974
130729	0.7991	457
130726	0.1906	83
130725	0.0491	10

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.22	gold quality
muscle of leg	UBERON:0001383	97.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.89	gold quality
muscle organ	UBERON:0001630	97.49	gold quality
biceps brachii	UBERON:0001507	97.12	gold quality
vastus lateralis	UBERON:0001379	96.57	gold quality
skeletal muscle tissue	UBERON:0001134	96.52	gold quality
quadriceps femoris	UBERON:0001377	96.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.32	gold quality
body of tongue	UBERON:0011876	96.30	gold quality
oocyte	CL:0000023	95.34	gold quality
diaphragm	UBERON:0001103	95.03	gold quality
deltoid	UBERON:0001476	95.03	gold quality
muscle tissue	UBERON:0002385	94.88	gold quality
olfactory bulb	UBERON:0002264	93.81	gold quality
left ventricle myocardium	UBERON:0006566	93.73	gold quality
tibialis anterior	UBERON:0001385	93.66	gold quality
tongue	UBERON:0001723	93.53	gold quality
apex of heart	UBERON:0002098	93.36	gold quality
heart left ventricle	UBERON:0002084	93.13	gold quality
cardiac ventricle	UBERON:0002082	93.07	gold quality
monocyte	CL:0000576	92.72	gold quality
cortical plate	UBERON:0005343	92.70	gold quality
mononuclear cell	CL:0000842	92.61	gold quality
leukocyte	CL:0000738	92.52	gold quality
cerebellar hemisphere	UBERON:0002245	92.42	gold quality
cerebellar cortex	UBERON:0002129	92.41	gold quality
secondary oocyte	CL:0000655	91.99	gold quality
islet of Langerhans	UBERON:0000006	91.88	gold quality
superior surface of tongue	UBERON:0007371	91.85	gold quality
cerebellum	UBERON:0002037	91.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.78	gold quality
adrenal tissue	UBERON:0018303	91.68	gold quality
heart	UBERON:0000948	91.59	gold quality
smooth muscle tissue	UBERON:0001135	91.46	gold quality
blood	UBERON:0000178	91.31	gold quality
cardia of stomach	UBERON:0001162	91.20	gold quality
rectum	UBERON:0001052	91.14	gold quality
prefrontal cortex	UBERON:0000451	90.82	gold quality
right atrium auricular region	UBERON:0006631	90.78	gold quality
right adrenal gland cortex	UBERON:0035827	90.75	gold quality
type B pancreatic cell	CL:0000169	90.74	silver quality
mucosa of stomach	UBERON:0001199	90.66	gold quality
cardiac atrium	UBERON:0002081	90.66	gold quality
vena cava	UBERON:0004087	90.61	gold quality
right adrenal gland	UBERON:0001233	90.52	gold quality
bone marrow	UBERON:0002371	90.49	gold quality
triceps brachii	UBERON:0001509	90.44	gold quality
lower lobe of lung	UBERON:0008949	90.24	gold quality
left adrenal gland	UBERON:0001234	90.23	gold quality
ganglionic eminence	UBERON:0004023	90.10	gold quality
adrenal gland	UBERON:0002369	89.97	gold quality
gluteal muscle	UBERON:0002000	89.96	gold quality
ventral tegmental area	UBERON:0002691	89.90	gold quality
myocardium	UBERON:0002349	89.80	gold quality
adrenal cortex	UBERON:0001235	89.79	gold quality
bone marrow cell	CL:0002092	89.71	gold quality
nipple	UBERON:0002030	89.62	gold quality
left adrenal gland cortex	UBERON:0035825	89.61	gold quality
pharyngeal mucosa	UBERON:0000355	89.54	gold quality
granulocyte	CL:0000094	89.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.41	gold quality
lymph node	UBERON:0000029	89.37	gold quality
medial globus pallidus	UBERON:0002477	89.32	gold quality
globus pallidus	UBERON:0001875	89.30	gold quality
nucleus accumbens	UBERON:0001882	89.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.19	gold quality
substantia nigra pars compacta	UBERON:0001965	89.18	gold quality
lower esophagus	UBERON:0013473	89.18	gold quality
right frontal lobe	UBERON:0002810	89.17	gold quality
heart right ventricle	UBERON:0002080	89.14	gold quality
cingulate cortex	UBERON:0003027	89.12	gold quality
anterior cingulate cortex	UBERON:0009835	89.10	gold quality
parotid gland	UBERON:0001831	89.05	gold quality
lateral globus pallidus	UBERON:0002476	89.04	gold quality
frontal cortex	UBERON:0001870	88.98	gold quality
pancreas	UBERON:0001264	88.97	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.82	gold quality
neocortex	UBERON:0001950	88.82	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.72	gold quality
popliteal artery	UBERON:0002250	88.65	gold quality
tibial artery	UBERON:0007610	88.65	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.64	gold quality
caudate nucleus	UBERON:0001873	88.62	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.53	gold quality
body of pancreas	UBERON:0001150	88.52	gold quality
tonsil	UBERON:0002372	88.52	gold quality
descending thoracic aorta	UBERON:0002345	88.51	gold quality
gingival epithelium	UBERON:0001949	88.49	gold quality
superior vestibular nucleus	UBERON:0007227	88.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.48	gold quality
pons	UBERON:0000988	88.45	gold quality
jejunum	UBERON:0002115	88.42	gold quality
seminal vesicle	UBERON:0000998	88.31	gold quality
subthalamic nucleus	UBERON:0001906	88.31	gold quality
right coronary artery	UBERON:0001625	88.29	gold quality
mammary duct	UBERON:0001765	88.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	273.6	low
Tongue	tissue	172.5
Retina	tissue	67.7
Bone marrow	tissue	58.2	medium
Pons	tissue	55.4
Hypothalamus	tissue	55.0
Midbrain	tissue	54.4
Basal ganglia	tissue	50.6	low
Septum	tissue	50.6
Thalamus	tissue	50.4
Cerebellum	tissue	47.7	high
Hippocampal formation	tissue	46.7
Cerebral cortex	tissue	45.0	low
Retrosplenial and cingulate cortex	tissue	45.0
Nucleus accumbens	tissue	44.6
Occipital cortex	tissue	44.2
Ventral forebrain	tissue	43.6
Postcentral gyrus	tissue	43.2
Entorhinal cortex	tissue	42.9
Somatosensory cortex	tissue	42.7
Heart muscle	tissue	42.5	medium
Frontal cortex	tissue	42.3
Putamen	tissue	41.9
Spinal cord	tissue	41.7
Amygdala	tissue	41.6
Locus coeruleus	tissue	41.0
Corpus callosum	tissue	40.4
Medulla oblongata	tissue	40.0
Substantia nigra	tissue	39.8
Retrosplenial cortex	tissue	39.4
Olfactory bulb	tissue	39.1
Caudate putamen	tissue	38.6
Hippocampus	tissue	37.8	medium
Choroid plexus	tissue	36.2
Parathyroid gland	tissue	31.4	medium
Thymus	tissue	27.4
Liver	tissue	26.4	medium
Kidney	tissue	25.9	high
Tonsil	tissue	25.1	medium
Rectum	tissue	25.0	medium
Smooth muscle	tissue	22.8	not detected
Lymph node	tissue	21.6	medium
Esophagus	tissue	21.4	low
Spleen	tissue	21.3	medium
Colon	tissue	20.6
Seminal vesicle	tissue	20.5	low
Pancreas	tissue	20.5	high
Ovary	tissue	20.3	medium
Epididymis	tissue	20.3	medium
Duodenum	tissue	20.3	medium
Skin 1	tissue	20.2	medium
Stomach 1	tissue	20.2	medium
Salivary gland	tissue	20.0	medium
Breast	tissue	19.9	medium
Prostate	tissue	19.4	medium
Small intestine	tissue	19.3	medium
Adrenal gland	tissue	19.1	medium
Appendix	tissue	18.9	medium
Adipose tissue	tissue	18.5	low
Endometrium 1	tissue	18.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Cerebellar cortex (70.9), Vermis (67.3), Flocculonodular lobe (67.2), Occipital cortex (white matter) (48.1), Parieto-temporal junction (white matter) (46.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASB8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 71 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745

Functional genomics

gnomAD constraint: pLI 0.000468, LOEUF 1, missense Z 1.56 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000317697 — one region, missense o/e 0.82.

Literature-anchored findings (GeneRIF, showing 2)

• molecular cloning and characterization of the human ASB-8 gene (PMID:12559969)
• E3 ubiquitin ligase ankyrin repeat and SOCS box-containing 8(ASB8) interacted with TBK1/IKKi and phosphorylation modification of ASB8 at site of Ser17 to further strengthen its ubiquitination activity were verified. Phosphorylated ASB8 accelerates K48-linked ubiquitination and degradation of TBK1/IKKi, which further reduces phosphorylation level of IRF3 and inhibits production of IFN-beta. (PMID:32298923)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb8	ENSDARG00000003383
mus_musculus	Asb8	ENSMUSG00000048175
rattus_norvegicus	Asb8	ENSRNOG00000075267
caenorhabditis_elegans		WBGENE00011270

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R544	100.0%	Diamond
Pongo abelii	Q5R6D7	99.7%	Diamond
Bos taurus	Q08E43	98.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6505	ncRNA	102466657
PFKM	protein-coding	5213
SENP1	protein-coding	29843
COL2A1	protein-coding	1280
CCDC184	protein-coding	387856

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 8 — Q9H765 (reviewed: Q9H765)

All UniProt accessions (10): Q9H765, F5GYF0, F5GZZ3, F5H023, F5H243, F5H5S9, F5H6A7, F5H772, F5H7B4, F8VS92

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. Inhibits IFN-beta production through the IRF3 signaling pathway by targeting TBK1 via ‘Lys-48’-linked ubiquitination, leading to its proteasomal degradation.

Subunit / interactions. Interacts with TBK1; this interaction promotes TBK1 proteasomal degradation.

Subcellular location. Cytoplasm.

Tissue specificity. Highest level of expression in skeletal muscle. Also expressed in heart, brain, placenta, liver, kidney and pancreas.

Post-translational modifications. Phosphorylated by TBK1.

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.

RefSeq proteins (7): NP_001306225, NP_001306226, NP_001306227, NP_001306228, NP_001306229, NP_001306230, NP_077000* (*=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
IPR037332	ASB8_SOCS	Domain

Pfam: PF07525, PF12796, PF13637

UniProt features (8 total): repeat 4, chain 1, domain 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
9OGD	Cryo-EM structure of human exportin-1 conjugated with selinexor and bound to human …	ELECTRON MICROSCOPY	2.49
9OGB	Cryo-EM structure of human exportin-1 conjugated with selinexor and bound to yeast …	ELECTRON MICROSCOPY	3.25
9OGE	Cryo-EM structure of human exportin-1 conjugated with KPT-127 and bound to human …	ELECTRON MICROSCOPY	3.28
9OGC	Cryo-EM structure of human exportin-1 conjugated with KPT-185 and bound to human …	ELECTRON MICROSCOPY	3.37
9OGF	Cryo-EM structure of human exportin-1 conjugated with KPT-UTSW1 and bound to human …	ELECTRON MICROSCOPY	4.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H765-F1	88.41	0.63

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Phosphoserine	17

Mutagenesis-validated functional residues (1)

Position	Phenotype
17	almost complete lost of phosphorylation by tbk1.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-8951664	Neddylation	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-983169	Class I MHC mediated antigen processing & presentation	—
R-HSA-168256	Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 107 (showing top): TGCGCANK_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, SCGGAAGY_ELK1_02, ER_Q6_02, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KASLER_HDAC7_TARGETS_1_UP, LIM_MAMMARY_STEM_CELL_DN, REACTOME_NEDDYLATION, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, ATF6_TARGET_GENES

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

5 top-level categories:

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

6 GO namespaces:

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

showing 15 of 592 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB8	RNF215	Q9Y6U7	532
ASB8	FAM217B	Q9NTX9	514
ASB8	PRR15L	Q9BU68	509
ASB8	CDC40	O60508	499
ASB8	LRRC30	A6NM36	480
ASB8	LRRC20	Q8TCA0	462
ASB8	ZNF646	O15015	452
ASB8	RBM47	A0AV96	451
ASB8	TM9SF3	Q9HD45	451
ASB8	TMEM192	Q8IY95	444
ASB8	KLHL30	Q0D2K2	415
ASB8	UBOX5	O94941	409
ASB8	TRAIP	Q9BWF2	399
ASB8	SCRN3	Q0VDG4	395
ASB8	LRRC14B	A6NHZ5	393

IntAct

Human interaction partners of ASB8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
VHL	physical association	0.560	3
ELOC	physical association	0.550	1
CUL5	association	0.530	1
USP33	physical association	0.400	1
HOXD4	physical association	0.370	1
MCM7	physical association	0.370	1
MYCBP2	physical association	0.370	1
RCN1	physical association	0.370	1
RIN3	physical association	0.370	1
SERTAD1	physical association	0.370	1
CUL4B	association	0.350	1
NPAT	association	0.350	1
TRIM11	association	0.350	1
CELF1	physical association	0.000	1

BioGRID (61 interactions; top human partners by supporting records): TCEB1 (Reconstituted Complex; 6 records), CUL5 (Affinity Capture-MS; 5 records), HIF1AN (Affinity Capture-MS; 5 records), TCEB2 (Affinity Capture-MS; 5 records), AMBRA1 (Affinity Capture-MS; 4 records), ESR2 (Affinity Capture-Western; 3 records), TRIM11 (Affinity Capture-MS; 3 records), IARS2 (Affinity Capture-MS; 2 records), NPAT (Affinity Capture-MS; 2 records), XPO1 (Affinity Capture-Western; 2 records), CUL4B (Affinity Capture-MS), DDA1 (Affinity Capture-MS), HOXD4 (Two-hybrid), KIF26B (Affinity Capture-MS), MCM7 (Two-hybrid)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
IKBKB	“up-regulates activity”	ASB8	phosphorylation
ASB8	“down-regulates quantity by destabilization”	IKBKB	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 14 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	6	17.8×	5e-05

Disease & clinical

Genetic variants

Variant evidence for ASB8: 46 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 536):

Position(s)	Effect	Δscore	Sites
12:48149999–48150000	acceptor_loss	1.0000	6
12:48151199–48151200	donor_loss	1.0000	5
12:48151306–48151307	acceptor_loss	1.0000	4
12:48151307	acceptor_loss	0.9900
12:48151524	donor_gain	0.9900
12:48157457–48157458	donor_loss	0.9900	5
12:48151306	acceptor_loss	0.9800
12:48151308	acceptor_gain	0.9800
12:48153266–48153267	donor_gain	0.9800	2
12:48151512	donor_gain	0.9500

AlphaMissense

798 missense substitutions predicted likely pathogenic (of 1,858 scored), across 194 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M62	9	0.930	0.992
D83	8	0.996	0.999
D115	8	0.994	0.998
D119	8	0.993	0.997
D148	8	0.992	0.999
D152	8	0.989	0.997
H91	8	0.982	0.995
H123	8	0.981	0.993
H58	8	0.972	0.996
N117	8	0.925	0.984
H51	8	0.901	0.965
W124	7	0.993	0.997
W157	7	0.991	0.997
F127	7	0.989	0.998
E95	7	0.971	0.991
C59	7	0.966	0.994
N181	7	0.941	0.995
C61	7	0.938	0.999
F32	7	0.921	0.983
N150	7	0.888	0.976

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.13e-06

Disease associations

OMIM: gene MIM:615053 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	5
Air Pollutants	decreases expression, affects expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Urethane	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.