ASB7

Summary

ASB7 (ankyrin repeat and SOCS box containing 7, HGNC:17182) is a protein-coding gene on chromosome 15q26.3, encoding Ankyrin repeat and SOCS box protein 7 (Q9H672). Substrate-recognition component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex, also named CRL5 complex), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as LZTS1, PSRC1 and SUV39H1.

The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contains a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. In this way, SOCS box containing proteins may regulate protein turnover by targeting proteins for polyubiquination and, therefore, for proteasome-mediated degradation. Two alternative transcripts encoding different isoforms have been described.

Source: NCBI Gene 140460 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 32 total
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.28 (highly constrained)
• MANE Select transcript: NM_198243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17182
Approved symbol	ASB7
Name	ankyrin repeat and SOCS box containing 7
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183475
Ensembl biotype	protein_coding
OMIM	615052
Entrez	140460

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

MANE Select: ENST00000332783

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

ENST00000332783, ENST00000343276, ENST00000558747, ENST00000561192, ENST00000899523, ENST00000899524, ENST00000899525, ENST00000929736, ENST00001132332

RefSeq mRNA: 2 — MANE Select: NM_198243 NM_024708, NM_198243

CCDS: CCDS10387, CCDS10388

Canonical transcript exons

ENST00000332783 — 6 exons

Exon	Start	End
ENSE00001300879	100609707	100609828
ENSE00001324819	100603215	100603313
ENSE00001368215	100612166	100612427
ENSE00001376832	100629437	100630042
ENSE00001380972	100648323	100651701
ENSE00001414915	100602589	100603046

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 85.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0404 / max 40.3156, expressed in 1723 samples.

Highest expression (Bgee): buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, palpebral conjunctiva, monocyte, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASB7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.7e-06	+0.09	15:100575503:A:G
Thyroid	eqtl	1.2e-02	-0.13	15:100265414:C:A
Brain Hippocampus	eqtl	1.5e-02	+0.95	15:99926339:G:A
Colon Sigmoid	eqtl	4.5e-02	-0.55	15:101123164:G:A
Brain Cortex	eqtl	4.7e-02	-0.99	15:101452776:T:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
148913	3.3025	1609
148914	1.7379	1160

Top tissues by expression

showing 100 of 271 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.74	gold quality
palpebral conjunctiva	UBERON:0001812	81.86	gold quality
monocyte	CL:0000576	79.54	gold quality
leukocyte	CL:0000738	79.49	gold quality
mononuclear cell	CL:0000842	79.26	gold quality
stromal cell of endometrium	CL:0002255	79.11	gold quality
ventricular zone	UBERON:0003053	78.67	gold quality
blood	UBERON:0000178	78.38	gold quality
granulocyte	CL:0000094	78.27	gold quality
pigmented layer of retina	UBERON:0001782	78.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.12	gold quality
amniotic fluid	UBERON:0000173	78.09	silver quality
cortical plate	UBERON:0005343	78.07	gold quality
parietal pleura	UBERON:0002400	78.01	gold quality
calcaneal tendon	UBERON:0003701	77.93	gold quality
middle temporal gyrus	UBERON:0002771	77.91	gold quality
rectum	UBERON:0001052	77.53	gold quality
colonic mucosa	UBERON:0000317	77.35	gold quality
visceral pleura	UBERON:0002401	77.33	gold quality
islet of Langerhans	UBERON:0000006	77.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.06	gold quality
pleura	UBERON:0000977	76.97	gold quality
mucosa of transverse colon	UBERON:0004991	76.95	gold quality
ganglionic eminence	UBERON:0004023	76.94	gold quality
corpus epididymis	UBERON:0004359	76.64	gold quality
endometrium	UBERON:0001295	76.63	gold quality
bone marrow	UBERON:0002371	76.56	gold quality
primary visual cortex	UBERON:0002436	75.84	gold quality
transverse colon	UBERON:0001157	75.64	gold quality
tendon	UBERON:0000043	75.47	gold quality
seminal vesicle	UBERON:0000998	75.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.31	gold quality
large intestine	UBERON:0000059	75.13	gold quality
colon	UBERON:0001155	75.01	gold quality
adrenal tissue	UBERON:0018303	74.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	74.95	gold quality
sural nerve	UBERON:0015488	74.87	gold quality
caput epididymis	UBERON:0004358	74.86	gold quality
lymph node	UBERON:0000029	74.37	gold quality
skin of hip	UBERON:0001554	74.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.31	gold quality
descending thoracic aorta	UBERON:0002345	74.29	gold quality
jejunal mucosa	UBERON:0000399	74.24	gold quality
intestine	UBERON:0000160	74.21	gold quality
upper leg skin	UBERON:0004262	74.12	gold quality
germinal epithelium of ovary	UBERON:0001304	73.97	gold quality
lower esophagus	UBERON:0013473	73.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	73.89	gold quality
tonsil	UBERON:0002372	73.87	gold quality
smooth muscle tissue	UBERON:0001135	73.77	gold quality
popliteal artery	UBERON:0002250	73.74	gold quality
tibial artery	UBERON:0007610	73.72	gold quality
epithelium of nasopharynx	UBERON:0001951	73.58	silver quality
right coronary artery	UBERON:0001625	73.56	gold quality
esophagus squamous epithelium	UBERON:0006920	73.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.35	gold quality
ovary	UBERON:0000992	73.31	gold quality
uterus	UBERON:0000995	73.23	gold quality
aorta	UBERON:0000947	73.21	gold quality
esophagus	UBERON:0001043	73.21	gold quality
colonic epithelium	UBERON:0000397	73.13	gold quality
gall bladder	UBERON:0002110	73.11	gold quality
cauda epididymis	UBERON:0004360	73.11	gold quality
left coronary artery	UBERON:0001626	73.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.08	gold quality
body of uterus	UBERON:0009853	73.06	gold quality
female reproductive system	UBERON:0000474	73.04	gold quality
lower esophagus mucosa	UBERON:0035834	73.03	gold quality
right lobe of liver	UBERON:0001114	72.98	gold quality
vagina	UBERON:0000996	72.94	gold quality
gastrocnemius	UBERON:0001388	72.90	gold quality
muscle of leg	UBERON:0001383	72.79	gold quality
bronchial epithelial cell	CL:0002328	72.77	gold quality
prostate gland	UBERON:0002367	72.74	gold quality
adipose tissue	UBERON:0001013	72.73	gold quality
prefrontal cortex	UBERON:0000451	72.72	gold quality
pancreatic ductal cell	CL:0002079	72.70	silver quality
connective tissue	UBERON:0002384	72.67	gold quality
thoracic aorta	UBERON:0001515	72.62	gold quality
left uterine tube	UBERON:0001303	72.61	gold quality
left adrenal gland	UBERON:0001234	72.57	gold quality
esophagus mucosa	UBERON:0002469	72.52	gold quality
urinary bladder	UBERON:0001255	72.46	gold quality
coronary artery	UBERON:0001621	72.42	gold quality
endocervix	UBERON:0000458	72.38	gold quality
pancreas	UBERON:0001264	72.38	gold quality
ascending aorta	UBERON:0001496	72.37	gold quality
left adrenal gland cortex	UBERON:0035825	72.36	gold quality
right adrenal gland cortex	UBERON:0035827	72.36	gold quality
ectocervix	UBERON:0012249	72.25	gold quality
oral cavity	UBERON:0000167	72.22	gold quality
tibia	UBERON:0000979	72.20	gold quality
right ovary	UBERON:0002118	72.14	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.13	gold quality
right adrenal gland	UBERON:0001233	72.10	gold quality
adrenal gland	UBERON:0002369	72.04	gold quality
omental fat pad	UBERON:0010414	71.99	gold quality
peritoneum	UBERON:0002358	71.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.57

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	12.1
Bone marrow	tissue	12.1	high
Nucleus accumbens	tissue	10.1
Postcentral gyrus	tissue	9.8
Hippocampus	tissue	9.0	low
Locus coeruleus	tissue	8.3
Corpus callosum	tissue	7.3
Putamen	tissue	6.6
Midbrain	tissue	6.5
Cerebellum	tissue	6.5	not detected
Thymus	tissue	6.5
Olfactory bulb	tissue	6.5
Colon	tissue	6.4
Thalamus	tissue	6.4
Testis	tissue	6.3	low
Cerebral cortex	tissue	6.3	low
Parathyroid gland	tissue	6.3	low
Superior colliculi	tissue	6.3
Substantia nigra	tissue	6.3
Liver	tissue	6.3	not detected
Kidney	tissue	6.3	high
Hippocampal formation	tissue	6.3
Occipital cortex	tissue	6.3
Epididymis	tissue	6.2	medium
Somatosensory cortex	tissue	6.2
Pons	tissue	6.1
Medulla oblongata	tissue	6.1
Spinal cord	tissue	6.1
Entorhinal cortex	tissue	6.1
Periaqueductal gray	tissue	6.1
Septum	tissue	6.0
Retrosplenial cortex	tissue	6.0
Temporal cortex	tissue	6.0
Lymph node	tissue	5.9	medium
Rectum	tissue	5.9	medium
Motor cortex	tissue	5.9
Amygdala	tissue	5.9
Hypothalamus	tissue	5.9
Tonsil	tissue	5.9	medium
Ventral forebrain	tissue	5.9
Retrosplenial and cingulate cortex	tissue	5.9
Prefrontal cortex	tissue	5.8
Thyroid gland	tissue	5.8	not detected
Insular cortex	tissue	5.8
Smooth muscle	tissue	5.6	not detected
Basal ganglia	tissue	5.6	not detected
Spleen	tissue	5.5	low
Ovary	tissue	5.4	high
Fallopian tube	tissue	5.3	medium
Endometrium 1	tissue	5.0	medium
Cervix	tissue	4.9	low
Urinary bladder	tissue	4.8	medium
Breast	tissue	4.7	medium
Retina	tissue	4.6
Lung	tissue	4.6	medium
Tongue	tissue	4.4
Prostate	tissue	4.4	not detected
Adipose tissue	tissue	4.3	low
Esophagus	tissue	4.3	not detected
Salivary gland	tissue	4.3	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Lateral funiculus (white matter) (10.8), Cerebellar cortex (10.7), Occipital cortex (white matter) (10.6), Ventromedial nucleus (10.6), Flocculonodular lobe (10.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASB7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-495-5P	97.62	68.28	682
HSA-MIR-4268	94.45	64.09	819

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.277, missense Z 4.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000332783 — one region, missense o/e 0.44.

Literature-anchored findings (GeneRIF, showing 2)

• these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3. (PMID:27697924)
• High ASB7 expression is associated with endoplasmic reticulum stress. (PMID:29630609)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asb7	ENSDARG00000006494
mus_musculus	Asb7	ENSMUSG00000030509
rattus_norvegicus	Asb7	ENSRNOG00000013795

Paralogs (3): ANK1 (ENSG00000029534), ANK2 (ENSG00000145362), ANK3 (ENSG00000151150)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2152835) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
enlarged heart	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal uterus morphology	1
anophthalmia	1
decreased locomotor activity	1
decreased exploration in new environment	1
abnormal skin morphology	1
abnormal eye morphology	1
increased circulating alkaline phosphatase level	1
increased kidney weight	1
enlarged uterus	1
increased cardiac muscle contractility	1
decreased CD8-positive, alpha-beta T cell number	1
enhanced cued conditioning behavior	1
decreased grip strength	1
dilated aorta	1
increased effector memory CD8-positive, alpha-beta T cell number	1
increased fasting circulating glucose level	1

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
Bos taurus	Q3SX00	100.0%	Diamond
Macaca fascicularis	Q9BGT9	99.7%	Diamond
Pongo abelii	Q5R8C8	99.6%	Diamond
Medicago truncatula	D3J163	54.8%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UMP3	45.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9UU77	43.6%	Diamond
Fowlpox virus strain NVSL	Q9J503	40.0%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UQV3	39.7%	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
LINS1	protein-coding	55180
GCAWKR	ncRNA	105369201

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 7 — Q9H672 (reviewed: Q9H672)

All UniProt accessions (2): Q9H672, H0YMJ1

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex, also named CRL5 complex), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as LZTS1, PSRC1 and SUV39H1. The ECS(ASB7) complex acts as a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1: ASB7 is recruited to heterochromatin by CBX5 (HP1 alpha), where it associates with SUV39H1, promoting the ubiquitin-proteasome-mediated degradation of SUV39H1. During mitosis, ASB7 is phosphorylated and inactivated, allowing SUV39H1 activity. The ECS(ASB7) complex also plays a role in spindle dynamics and genome integrity by targeting the mitotic progression protein PSRC1 for proteasomal degradation in a cell cycle-dependent manner. Also participates in meiosis by mediating the proper attachment between kinetochores and microtubules.

Subunit / interactions. Substrate-recognition component of the ECS(ASB7) complex, composed of ASB7, CUL5, ELOB, ELOC and RNF7/RBX2. Interacts (via PxVxL motif 1) with CBX5 (HP1 alpha); leading to its recruitment to heterochromatin.

Subcellular location. Chromosome. Nucleus.

Post-translational modifications. Phosphorylated by CDK1 during mitosis, preventing its association with SUV39H1 substrate.

Domain organisation. The PxVxL motif 1 mediates interaction with CBX5 (HP1 alpha). 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?
Q9H672-1	1	yes
Q9H672-2	2

RefSeq proteins (2): NP_078984, NP_937886* (*=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
IPR037326	ASB7_SOCS	Domain

Pfam: PF07525, PF12796

UniProt features (63 total): mutagenesis site 20, helix 20, repeat 8, short sequence motif 3, modified residue 3, turn 3, splice variant 2, chain 1, sequence conflict 1, strand 1, domain 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8Y1U	Crystal structure of ASB7-Elongin B/C bound to the LZTS1-degron	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H672-F1	92.09	0.80

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; vesicles; nucleoplasm

Antibody reliability (HPA): IH approved · IF 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 (3)

Type	Positions
Phosphothreonine	119, 152, 216

Mutagenesis-validated functional residues (20)

Position	Phenotype
65–67	abolished interaction with cbx5, preventing recruitment to heterochromatin.
82	strongly decreased affinity for lzts1 substrate.
87	does not affect affinity for lzts1 substrate.
116	decreased affinity for lzts1 substrate.
118	strongly decreased affinity for lzts1 substrate.
119	abolished phosphorylation by cdk1; when associated with a-152 and a-216.
119	mimics phosphorylation; strongly decreased ability to promote suv39h1 ubiquitination; when associated with a-152 and a-216.
126	does not affect affinity for lzts1 substrate.
127	does not affect affinity for lzts1 substrate.
147	strongly decreased affinity for lzts1 substrate.
151	strongly decreased affinity for lzts1 substrate.
152	abolished phosphorylation by cdk1; when associated with a-119 and a-216.
152	mimics phosphorylation; strongly decreased ability to promote suv39h1 ubiquitination; when associated with a-119 and a-216.
160	decreased affinity for lzts1 substrate.
182	decreased affinity for lzts1 substrate.
185	decreased affinity for lzts1 substrate.
186	does not affect affinity for lzts1 substrate.
189	does not affect affinity for lzts1 substrate.
216	abolished phosphorylation by cdk1; when associated with a-119 and a-152.
216	mimics phosphorylation; strongly decreased ability to promote suv39h1 ubiquitination; when associated with a-119 and a-152.

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: 211 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, PAX4_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, NKX25_02, SP3_Q3, GOBP_CHROMOSOME_LOCALIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RACCACAR_AML_Q6, FOXO1_01

GO Biological Process (4): protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), regulation of heterochromatin organization (GO:0120261)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (5): heterochromatin (GO:0000792), nucleus (GO:0005634), cytosol (GO:0005829), Cul5-RING ubiquitin ligase complex (GO:0031466), chromosome (GO:0005694)

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
protein modification by small protein conjugation	1
intracellular anatomical structure	1
signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
heterochromatin organization	1
regulation of chromatin organization	1
enzyme-substrate adaptor activity	1
binding	1
chromatin	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	direct assay
regulation of heterochromatin organization	BP	direct assay
Cul5-RING ubiquitin ligase complex	CC	direct assay
heterochromatin	CC	direct assay
ubiquitin-like ligase-substrate adaptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 726 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB7	CCDC127	Q96BQ5	732
ASB7	SUPT7L	O94864	697
ASB7	VCF1	Q969W3	674
ASB7	TADA2B	Q86TJ2	651
ASB7	ASB6	Q9NWX5	638
ASB7	MTO1	Q9Y2Z2	579
ASB7	AARS1	P49588	566
ASB7	KLHL42	Q9P2K6	513
ASB7	FBXO9	Q9UK97	490
ASB7	CNOT10	Q9H9A5	486
ASB7	ZNRD2	O60232	458
ASB7	TMTC2	Q8N394	457
ASB7	ELP4	Q96EB1	444
ASB7	THSD7B	Q9C0I4	441
ASB7	ARIH2	O95376	434

IntAct

Human interaction partners of ASB7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
CUL5	physical association	0.740	1
CCDC136	physical association	0.670	3
HMBOX1	physical association	0.670	3
RNF7	physical association	0.670	1
POLR3A	association	0.530	2
TRIP11	association	0.530	1
ATF4	physical association	0.370	1
HSCB	physical association	0.370	1

BioGRID (116 interactions; top human partners by supporting records): CUL5 (Affinity Capture-Western; 8 records), PSRC1 (Affinity Capture-MS; 5 records), CCDC136 (Two-hybrid; 4 records), HIF1AN (Affinity Capture-MS; 4 records), HMBOX1 (Two-hybrid; 4 records), C8orf34 (Affinity Capture-MS; 3 records), COLEC11 (Affinity Capture-MS; 3 records), OGN (Affinity Capture-MS; 3 records), RABEP2 (Affinity Capture-MS; 3 records), RNF7 (Affinity Capture-MS; 3 records), SEPT1 (Affinity Capture-MS; 3 records), ZFAND2B (Affinity Capture-MS; 3 records), ADAM33 (Affinity Capture-MS; 2 records), AGRP (Affinity Capture-MS; 2 records), ANKRD13A (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Ubiquitin E3 ligase (ASB7, TCEB1, TCEB2, CUL5, RNF7)	5	ASB7, CUL5, ELOB, ELOC, RNF7

Disease & clinical

Genetic variants

Variant evidence for ASB7: 32 ClinVar records (0 pathogenic / likely pathogenic); 17 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	5

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 568):

Position(s)	Effect	Δscore	Sites
15:100603047	donor_loss	1.0000
15:100603213–100603214	acceptor_loss	1.0000	6
15:100603314–100603315	donor_loss	1.0000	3
15:100608033	donor_gain	1.0000
15:100608062	donor_gain	1.0000
15:100609705–100609706	acceptor_loss	1.0000	6
15:100612163	acceptor_gain	1.0000
15:100612164–100612165	acceptor_loss	1.0000	6
15:100612390	donor_gain	1.0000
15:100612395	donor_gain	1.0000

AlphaMissense

1,124 missense substitutions predicted likely pathogenic (of 2,076 scored), across 246 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
M90	9	0.956	0.996
D77	8	0.998	0.999
H86	8	0.996	0.999
H122	8	0.996	0.999
D116	8	0.994	0.999
H52	8	0.989	0.998
H126	8	0.988	0.999
D213	8	0.987	0.996
H219	8	0.976	0.997
F82	8	0.973	1.000
S147	8	0.964	0.999
H91	8	0.958	0.994
F182	8	0.957	0.999
D44	8	0.956	0.991
S114	8	0.953	0.999
F132	8	0.953	0.997
D144	8	0.930	0.990
N244	8	0.915	0.998
F199	8	0.899	0.996
F66	8	0.883	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.05e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000507

Disease associations

OMIM: gene MIM:615052 | disease phenotypes:

GWAS associations

17 associations:

Study	Trait	p-value
GCST009724_95	Vertical cup-disc ratio (multi-trait analysis)	2e-20
GCST007565_128	Morning person	2e-15
GCST007576_252	Chronotype	2e-15
GCST009723_46	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2e-13
GCST003989_29	Chin dimples	9e-13
GCST004075_4	Vertical cup-disc ratio	3e-12
GCST004137_18	Optic cup area	1e-10
GCST004075_3	Vertical cup-disc ratio	2e-9
GCST009412_18	Vertical cup-disc ratio	3e-9
GCST002764_5	Optic cup area	1e-8
GCST004076_25	Optic disc area	4e-8
GCST009404_10	Optic cup area	4e-8
GCST010993_3	Anti-drug antibodies in autoimmune disease (time to event)	6e-7
GCST004137_7	Optic cup area	8e-7
GCST001694_8	Response to taxane treatment (paclitaxel)	1e-6
GCST004493_7	Lower body strength	2e-6
GCST002764_11	Optic cup area	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0007999	lower body strength measurement
EFO:0008328	chronotype measurement
EFO:0010559	anti-drug antibody measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Plant Oils	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 285 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects