ASB4

Summary

ASB4 (ankyrin repeat and SOCS box containing 4, HGNC:16009) is a protein-coding gene on chromosome 7q21.3, encoding Ankyrin repeat and SOCS box protein 4 (Q9Y574). 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 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 some of the full length sequences are not known.

Source: NCBI Gene 51666 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 81 total — 5 pathogenic
• GTEx eGene: eQTL in 33 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.23 (unconstrained)
• MANE Select transcript: NM_016116
• Notable: 81 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16009
Approved symbol	ASB4
Name	ankyrin repeat and SOCS box containing 4
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Aliases	ASB-4
Ensembl gene	ENSG00000005981
Ensembl biotype	protein_coding
OMIM	605761
Entrez	51666

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000325885

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

ENST00000325885, ENST00000257621, ENST00000428113, ENST00000896495, ENST00000965611, ENST00001113475, ENST00001128528, ENST00001128529, ENST00001134263

RefSeq mRNA: 2 — MANE Select: NM_016116 NM_016116, NM_145872

CCDS: CCDS5641, CCDS5642

Canonical transcript exons

ENST00000325885 — 5 exons

Exon	Start	End
ENSE00000706251	95495758	95496057
ENSE00000977228	95536437	95536550
ENSE00001268050	95537571	95540233
ENSE00001268089	95527813	95528303
ENSE00003844324	95485943	95486158

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 96.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3477 / max 129.6064, expressed in 40 samples.

Highest expression (Bgee): adrenal tissue, adrenal gland cortex, adrenal gland, adrenal cortex, biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASB4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	4.3e-66	+0.84	7:95397441:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-54	+0.83	7:95397441:T:C
Nerve Tibial	eqtl	3.1e-52	+0.75	7:95397441:T:C
Thyroid	eqtl	7.0e-43	+0.79	7:95397441:T:C
Adipose Visceral Omentum	eqtl	8.8e-38	+0.71	7:95397096:G:A
Ovary	eqtl	2.6e-27	+0.99	7:95396917:C:T
Breast Mammary Tissue	eqtl	1.4e-22	+0.59	7:95397096:G:A
Adipose Subcutaneous	eqtl	5.8e-22	+0.59	7:95397096:G:A
Testis	eqtl	1.5e-18	+0.44	7:95366207:T:C
Lung	eqtl	2.4e-18	+0.47	7:95397441:T:C
Stomach	eqtl	9.3e-17	+0.73	7:95397015:A:G
Pancreas	eqtl	2.6e-15	+0.58	7:95400389:T:A
Prostate	eqtl	6.1e-15	+0.73	7:95396288:G:A
Esophagus Gastroesophageal Junction	eqtl	1.4e-12	+0.59	7:95397015:A:G
Pituitary	sqtl	1.8e-12	-0.72	7:95494158:A:G
Pituitary	eqtl	5.0e-10	+0.27	7:95499441:G:A
Small Intestine Terminal Ileum	eqtl	2.0e-08	+0.65	7:95397096:G:A
Colon Transverse	eqtl	1.2e-07	+0.45	7:95404529:C:T
Brain Hypothalamus	eqtl	6.6e-07	+0.39	7:95397015:A:G
Colon Sigmoid	eqtl	7.0e-07	+0.46	7:95406270:A:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
79753	0.1723	30
79749	0.0634	8
79751	0.0533	13
79752	0.0290	14
79754	0.0165	9
79750	0.0131	4

Top tissues by expression

showing 100 of 274 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.66	gold quality
right adrenal gland cortex	UBERON:0035827	94.91	gold quality
right adrenal gland	UBERON:0001233	94.32	gold quality
left adrenal gland	UBERON:0001234	93.94	gold quality
left adrenal gland cortex	UBERON:0035825	93.69	gold quality
adrenal cortex	UBERON:0001235	93.66	gold quality
adrenal gland	UBERON:0002369	92.38	gold quality
biceps brachii	UBERON:0001507	90.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.26	gold quality
vastus lateralis	UBERON:0001379	83.56	gold quality
gastrocnemius	UBERON:0001388	82.80	gold quality
muscle of leg	UBERON:0001383	82.38	gold quality
muscle organ	UBERON:0001630	82.33	gold quality
skeletal muscle tissue	UBERON:0001134	81.96	gold quality
quadriceps femoris	UBERON:0001377	81.62	gold quality
endothelial cell	CL:0000115	80.02	gold quality
pituitary gland	UBERON:0000007	77.65	gold quality
muscle tissue	UBERON:0002385	77.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.32	gold quality
buccal mucosa cell	CL:0002336	77.25	gold quality
deltoid	UBERON:0001476	77.12	silver quality
islet of Langerhans	UBERON:0000006	75.10	gold quality
hair follicle	UBERON:0002073	72.41	gold quality
adenohypophysis	UBERON:0002196	72.30	gold quality
diaphragm	UBERON:0001103	72.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.95	gold quality
tibialis anterior	UBERON:0001385	68.91	silver quality
apex of heart	UBERON:0002098	68.88	gold quality
spinal cord	UBERON:0002240	68.72	gold quality
substantia nigra	UBERON:0002038	68.13	gold quality
midbrain	UBERON:0001891	67.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.89	gold quality
putamen	UBERON:0001874	66.29	gold quality
tongue squamous epithelium	UBERON:0006919	64.46	gold quality
caudate nucleus	UBERON:0001873	64.14	gold quality
medial globus pallidus	UBERON:0002477	64.04	silver quality
amygdala	UBERON:0001876	63.59	gold quality
heart left ventricle	UBERON:0002084	63.48	gold quality
pancreas	UBERON:0001264	63.38	gold quality
cardiac ventricle	UBERON:0002082	63.31	gold quality
right lobe of liver	UBERON:0001114	63.26	gold quality
globus pallidus	UBERON:0001875	62.67	silver quality
substantia nigra pars compacta	UBERON:0001965	62.53	silver quality
placenta	UBERON:0001987	62.30	gold quality
left ventricle myocardium	UBERON:0006566	62.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	61.87	gold quality
hypothalamus	UBERON:0001898	61.47	gold quality
pancreatic ductal cell	CL:0002079	61.27	silver quality
substantia nigra pars reticulata	UBERON:0001966	60.57	gold quality
olfactory bulb	UBERON:0002264	60.57	gold quality
cerebellar vermis	UBERON:0004720	60.41	gold quality
body of tongue	UBERON:0011876	60.39	gold quality
germinal epithelium of ovary	UBERON:0001304	60.38	gold quality
type B pancreatic cell	CL:0000169	60.33	gold quality
thymus	UBERON:0002370	60.21	gold quality
heart	UBERON:0000948	60.14	gold quality
forebrain	UBERON:0001890	60.14	gold quality
nucleus accumbens	UBERON:0001882	60.12	gold quality
liver	UBERON:0002107	60.03	gold quality
temporal lobe	UBERON:0001871	59.60	gold quality
cardiac atrium	UBERON:0002081	59.47	gold quality
myocardium	UBERON:0002349	59.18	gold quality
tongue	UBERON:0001723	58.97	silver quality
endometrium epithelium	UBERON:0004811	58.93	gold quality
prefrontal cortex	UBERON:0000451	58.85	gold quality
body of pancreas	UBERON:0001150	58.81	gold quality
right atrium auricular region	UBERON:0006631	58.80	gold quality
upper arm skin	UBERON:0004263	58.74	gold quality
central nervous system	UBERON:0001017	58.69	gold quality
trachea	UBERON:0003126	58.61	gold quality
telencephalon	UBERON:0001893	58.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.47	gold quality
brain	UBERON:0000955	58.37	gold quality
renal medulla	UBERON:0000362	58.35	gold quality
cingulate cortex	UBERON:0003027	58.21	gold quality
saphenous vein	UBERON:0007318	58.17	gold quality
pericardium	UBERON:0002407	58.04	gold quality
anterior cingulate cortex	UBERON:0009835	57.93	gold quality
synovial joint	UBERON:0002217	57.86	silver quality
Ammon’s horn	UBERON:0001954	57.82	gold quality
inferior vagus X ganglion	UBERON:0005363	57.77	gold quality
right frontal lobe	UBERON:0002810	57.76	gold quality
nipple	UBERON:0002030	57.69	gold quality
urethra	UBERON:0000057	57.66	gold quality
pharyngeal mucosa	UBERON:0000355	57.64	gold quality
pons	UBERON:0000988	57.41	gold quality
pylorus	UBERON:0001166	57.41	gold quality
superior surface of tongue	UBERON:0007371	57.40	gold quality
trigeminal ganglion	UBERON:0001675	57.37	gold quality
dorsal root ganglion	UBERON:0000044	57.33	gold quality
nasal cavity epithelium	UBERON:0005384	57.31	gold quality
penis	UBERON:0000989	57.22	gold quality
cardia of stomach	UBERON:0001162	57.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.10	gold quality
frontal cortex	UBERON:0001870	57.07	gold quality
lateral globus pallidus	UBERON:0002476	56.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	56.89	gold quality
neocortex	UBERON:0001950	56.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36
E-ENAD-27	yes	3.85
E-MTAB-7303	no	158.01

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 72 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Adrenal gland	tissue	38.0
Skeletal muscle	tissue	32.0
Tongue	tissue	9.8
Locus coeruleus	tissue	8.3
Nucleus accumbens	tissue	8.0
Pituitary gland	tissue	7.9
Choroid plexus	tissue	7.6
Hippocampus	tissue	7.5
Postcentral gyrus	tissue	7.1
Substantia nigra	tissue	6.6
Placenta	tissue	1.9
Heart muscle	tissue	1.8
Liver	tissue	1.4
Retina	tissue	1.2
Midbrain	tissue	1.0
Caudate putamen	tissue	0.7
Stomach 1	tissue	0.6
Salivary gland	tissue	0.6
Pancreas	tissue	0.6
Superior colliculi	tissue	0.6
Lung	tissue	0.6
Prefrontal cortex	tissue	0.5
Cerebral cortex	tissue	0.5
Thalamus	tissue	0.5
Bone marrow	tissue	0.5
Hippocampal formation	tissue	0.5
Ovary	tissue	0.4
Motor cortex	tissue	0.4
Putamen	tissue	0.4
Amygdala	tissue	0.4
Small intestine	tissue	0.4
Entorhinal cortex	tissue	0.4
Ventral forebrain	tissue	0.4
Septum	tissue	0.4
Retrosplenial cortex	tissue	0.4
Temporal cortex	tissue	0.4
Insular cortex	tissue	0.4
Skin 1	tissue	0.3
Lymph node	tissue	0.3
Breast	tissue	0.3
Testis	tissue	0.3
Pons	tissue	0.3
Frontal cortex	tissue	0.3
Basal ganglia	tissue	0.3
Hypothalamus	tissue	0.3
Thyroid gland	tissue	0.3
Spleen	tissue	0.3
Duodenum	tissue	0.3
Spinal cord	tissue	0.3
Corpus callosum	tissue	0.3
Retrosplenial and cingulate cortex	tissue	0.3
Periaqueductal gray	tissue	0.3
Fallopian tube	tissue	0.3
Somatosensory cortex	tissue	0.3
Occipital cortex	tissue	0.3
Seminal vesicle	tissue	0.2
Esophagus	tissue	0.2
Epididymis	tissue	0.2
Medulla oblongata	tissue	0.2
Gallbladder	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Ventral tegmental area (11.2), Median raphe nucleus (10.0), Lateral parabrachial nucleus (9.8), Nucleus raphe obscurus (9.8), Parieto-temporal junction (white matter) (9.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASB4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 114 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220

Functional genomics

gnomAD constraint: pLI 5.31e-10, LOEUF 1.23, missense Z -0.0662 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000325885 — one region, missense o/e 1.06.

Literature-anchored findings (GeneRIF, showing 3)

• Based on its differential expression, neuroanatomical distribution and colocalisation, we hypothesise that rat Asb-4 is a gene involved in energy homeostasis. (PMID:15929745)
• This analysis identified an antigen, ASB4, which was processed and presented by a cancer stem cell (CSC) subset but not by non-CSCs. The ASB4 gene was expressed in CSCs of colorectal cancer, but not in cells that had differentiated into non-CSCs.ASB4 is a tumor-associated antigen that can elicit CTL responses specific to CSCs and can discriminate between two cellular subsets of colorectal cancer. (PMID:29371260)
• The Roles of Obesity and ASB4 in Preeclampsia Pathogenesis. (PMID:39201703)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb4	ENSDARG00000034988
mus_musculus	Asb4	ENSMUSG00000042607
rattus_norvegicus	Asb4	ENSRNOG00000009197

Paralogs (7): ASB3 (ENSG00000115239), ASB15 (ENSG00000146809), ASB10 (ENSG00000146926), ASB16 (ENSG00000161664), ASB18 (ENSG00000182177), MPHOSPH8 (ENSG00000196199), ASB14 (ENSG00000239388)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1929751) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased litter size	2
hypertension	1
abnormal coat/ hair morphology	1
abnormal spleen morphology	1
abnormal testis morphology	1
decreased trophoblast giant cell number	1
abnormal placenta labyrinth morphology	1
embryonic growth arrest	1
abnormal extraembryonic tissue morphology	1
abnormal epididymis morphology	1
albuminuria	1
abnormal placenta vasculature	1
abnormal pregnancy	1
abnormal blood pressure regulation	1
increased airway resistance	1
abnormal glomerular capillary morphology	1
abnormal glomerular mesangium morphology	1
abnormal urine albumin level	1

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
PDK4	protein-coding	5166
PON2	protein-coding	5445
PON3	protein-coding	5446
PDK4-AS1	ncRNA	107986824
PON1	protein-coding	5444

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 4 — Q9Y574 (reviewed: Q9Y574)

All UniProt accessions (1): Q9Y574

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. Promotes differentiation and maturation of the vascular lineage by an oxygen-dependent mechanism. Also acts as a negative regulator of GPS1, a component of the COP9 signalosome (CSN) multiprotein complex, thereby inhibiting the serine phosphorylation of IRS1. Regulates IRS4 levels by directing its degradation via ubiquitination and thereby decreases the downstream signal of IRS4. Plays a critical role during early vascular development and proper placentation. Mechanistically, negatively regulates the transcriptional regulator inhibitor of DNA binding 2/ID2 expression through polyubiquitination and proteasome dependent degradation.

Subunit / interactions. Interacts with HIF1AN. Component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex formed of CUL2 or CUL5, Elongin BC (ELOB and ELOC), RBX1 and ASB4. Interacts with IRS4. Interacts with ID2.

Subcellular location. Cytoplasm.

Post-translational modifications. Hydroxylation at Asn-246 by HIF1AN may provide an oxygen-dependent regulation mechanism for the function of ASB4 in promoting vascular differentiation.

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?
Q9Y574-1	1	yes
Q9Y574-2	2

RefSeq proteins (2): NP_057200, NP_665879 (=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 (14 total): repeat 6, region of interest 2, chain 1, site 1, modified residue 1, splice variant 1, sequence variant 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y574-F1	92.69	0.84

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Catalytic / active sites (1)

Position	Role
256	essential for interaction with hif1an

Post-translational modifications (1)

Type	Positions
(3s)-3-hydroxyasparagine	246

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: 162 (showing top): GOBP_REGULATION_OF_VASCULOGENESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, TAL1ALPHAE47_01, AAAYRNCTG_UNKNOWN, MORF_RAD51L3, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, TGCTGAY_UNKNOWN, GOBP_PROTEIN_AUTOUBIQUITINATION, WTGAAAT_UNKNOWN, GOBP_BLOOD_VESSEL_MORPHOGENESIS, TGACATY_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_VASCULOGENESIS

GO Biological Process (4): intracellular signal transduction (GO:0035556), protein autoubiquitination (GO:0051865), positive regulation of vasculogenesis (GO:2001214), protein ubiquitination (GO:0016567)

GO Molecular Function (4): ubiquitin-protein transferase activity (GO:0004842), ubiquitin protein ligase binding (GO:0031625), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), Cul2-RING ubiquitin ligase complex (GO:0031462), Cul5-RING ubiquitin ligase complex (GO:0031466), 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

15 GO namespaces:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
cullin-RING ubiquitin ligase complex	2
signal transduction	1
protein ubiquitination	1
vasculogenesis	1
positive regulation of cell differentiation	1
regulation of vasculogenesis	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
Cul2-RING ubiquitin ligase complex	CC	direct assay
Cul5-RING ubiquitin ligase complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 894 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB4	CISH	Q9NSE2	779
ASB4	JAK3	P52333	640
ASB4	PPP1R9A	Q9ULJ8	566
ASB4	SGCE	O43556	562
ASB4	COPG2	Q9UBF2	527
ASB4	CASD1	Q96PB1	512
ASB4	ASB6	Q9NWX5	506
ASB4	BLCAP	P62952	502
ASB4	TRAPPC9	Q96Q05	490
ASB4	DRC11L	A6NCM1	460
ASB4	PEG10	Q86TG7	452
ASB4	ASB15	Q8WXK1	450
ASB4	TMEM233	B4DJY2	441
ASB4	NNAT	Q16517	432
ASB4	SBK3	P0C264	427

IntAct

Human interaction partners of ASB4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
DNAJB5	association	0.530	2
HSP90AB1	physical association	0.400	1
AKAP10	association	0.350	1
ZNF195	association	0.350	1

BioGRID (50 interactions; top human partners by supporting records): HIF1AN (Affinity Capture-MS; 5 records), DNAJB5 (Affinity Capture-MS; 4 records), CUL5 (Affinity Capture-Western; 3 records), ID2 (Affinity Capture-Western; 3 records), ASB7 (Affinity Capture-MS; 2 records), CUL4A (Affinity Capture-MS; 2 records), GPS1 (Affinity Capture-Western; 2 records), TUBB8 (Affinity Capture-MS; 2 records), CUL2 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DNAJB4 (Affinity Capture-MS), FARSA (Affinity Capture-MS), HAUS8 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-Luminescence), HSPB1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
ASB4	“down-regulates quantity by destabilization”	ID2	polyubiquitination

Disease & clinical

Genetic variants

Variant evidence for ASB4: 81 ClinVar records (5 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	70
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
976777	GRCh37/hg19 7q21.3(chr7:93516132-95668733)	Pathogenic	criteria provided, single submitter	1
1808653	GRCh37/hg19 7q21.2-22.1(chr7:92721627-98311537)x1	Pathogenic	criteria provided, single submitter	1
2685252	GRCh37/hg19 7q21.3(chr7:94813388-96264152)x1	Pathogenic	criteria provided, single submitter	1
146112	GRCh38/hg38 7q21.3(chr7:95127070-97873487)x1	Pathogenic	no assertion criteria provided	1
153321	GRCh38/hg38 7q21.2-21.3(chr7:92759144-97568646)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ASB4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 419):

Position(s)	Effect	Δscore	Sites
7:95527810	acceptor_gain	1.0000
7:95527811–95527812	acceptor_loss	1.0000	4
7:95528304–95528305	donor_loss	1.0000	5
7:95486159–95486160	donor_loss	0.9900	5
7:95527811–95527812	acceptor_loss	0.9900	2
7:95528305	donor_loss	0.9900
7:95536435–95536436	acceptor_loss	0.9900	6
7:95536551–95536552	donor_loss	0.9900	5
7:95527799	acceptor_gain	0.9800
7:95536552	donor_loss	0.9800

AlphaMissense

1,266 missense substitutions predicted likely pathogenic (of 2,823 scored), across 318 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
D282	8	0.994	0.998
D52	8	0.980	0.993
H80	8	0.977	0.996
D45	8	0.950	0.991
D264	8	0.949	0.991
H112	8	0.943	0.990
F324	8	0.943	0.997
H257	8	0.941	0.982
H386	8	0.937	0.984
D251	8	0.934	0.976
N106	8	0.927	0.997
H145	8	0.926	0.978
F48	8	0.916	0.993
D249	8	0.913	0.986
F369	8	0.900	0.989
H180	8	0.887	0.967
D43	8	0.846	0.905
W65	7	0.989	0.998
W75	7	0.988	0.998
W261	7	0.988	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Stomach Adenocarcinoma)

Disease associations

OMIM: gene MIM:605761 | disease phenotypes:

GWAS associations

10 associations:

Study	Trait	p-value
GCST002783_145	Body mass index	5e-8
GCST004495_143	BMI (adjusted for smoking behaviour)	6e-7
GCST004497_96	Body mass index (joint analysis main effects and smoking interaction)	7e-7
GCST004495_142	BMI (adjusted for smoking behaviour)	8e-7
GCST002783_195	Body mass index	2e-6
GCST002783_573	Body mass index	2e-6
GCST004497_97	Body mass index (joint analysis main effects and smoking interaction)	2e-6
GCST009391_1361	Metabolite levels	6e-6
GCST002985_7	Middle childhood and early adolescence aggressive behavior	8e-6
GCST009391_1331	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0010405	triacylglycerol 48:2 measurement
EFO:0010410	triacylglycerol 50:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Valproic Acid	increases expression	2
OTX015	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Folic Acid	decreases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT05671068	Not specified	COMPLETED	EMOTION & COGNITION IN MYOCLONUS DYSTONIA (AGENT10-ECODYST)