ASB18

Summary

ASB18 (ankyrin repeat and SOCS box containing 18, HGNC:19770) is a protein-coding gene on chromosome 2q37.2, encoding Ankyrin repeat and SOCS box protein 18 (Q6ZVZ8). May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation.

Source: NCBI Gene 401036 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 100 total — 1 pathogenic
• MANE Select transcript: NM_212556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19770
Approved symbol	ASB18
Name	ankyrin repeat and SOCS box containing 18
Location	2q37.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182177
Ensembl biotype	protein_coding
OMIM	621134
Entrez	401036

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000409749, ENST00000430053, ENST00000447030, ENST00000469508, ENST00000487961, ENST00000645891

RefSeq mRNA: 1 — MANE Select: NM_212556 NM_212556

CCDS: CCDS46548

Canonical transcript exons

ENST00000409749 — 6 exons

Exon	Start	End
ENSE00001578622	236214362	236214866
ENSE00001582046	236241280	236241402
ENSE00001588804	236237689	236237956
ENSE00001589182	236264141	236264406
ENSE00001794748	236196272	236196385
ENSE00003928184	236193459	236195057

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 86.04.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	86.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.52	gold quality
heart left ventricle	UBERON:0002084	77.99	gold quality
skeletal muscle tissue	UBERON:0001134	73.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.78	gold quality
heart	UBERON:0000948	68.14	gold quality
muscle of leg	UBERON:0001383	65.86	gold quality
right atrium auricular region	UBERON:0006631	65.36	gold quality
gastrocnemius	UBERON:0001388	64.52	gold quality
muscle tissue	UBERON:0002385	60.62	gold quality
putamen	UBERON:0001874	53.00	gold quality
cortical plate	UBERON:0005343	51.64	gold quality
superior frontal gyrus	UBERON:0002661	50.90	gold quality
colonic epithelium	UBERON:0000397	45.40	gold quality
caudate nucleus	UBERON:0001873	45.31	gold quality
primary visual cortex	UBERON:0002436	44.59	gold quality
nucleus accumbens	UBERON:0001882	44.43	gold quality
prefrontal cortex	UBERON:0000451	43.41	gold quality
ganglionic eminence	UBERON:0004023	41.84	gold quality
bone marrow cell	CL:0002092	41.58	gold quality
frontal cortex	UBERON:0001870	41.14	gold quality
popliteal artery	UBERON:0002250	40.88	gold quality
tibial artery	UBERON:0007610	40.83	gold quality
mucosa of transverse colon	UBERON:0004991	38.89	silver quality
tonsil	UBERON:0002372	38.38	silver quality
cerebral cortex	UBERON:0000956	38.10	gold quality
brain	UBERON:0000955	38.00	gold quality
right frontal lobe	UBERON:0002810	37.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	36.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.39

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asb18	ENSMUSG00000067081
rattus_norvegicus	Asb18	ENSRNOG00000019557
drosophila_melanogaster	CG9121	FBGN0031675
drosophila_melanogaster	CG13933	FBGN0035270

Paralogs (7): ASB4 (ENSG00000005981), ASB3 (ENSG00000115239), ASB15 (ENSG00000146809), ASB10 (ENSG00000146926), ASB16 (ENSG00000161664), MPHOSPH8 (ENSG00000196199), ASB14 (ENSG00000239388)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 18 — Q6ZVZ8 (reviewed: Q6ZVZ8)

All UniProt accessions (3): Q6ZVZ8, C9JFL4, H7C3E8

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.

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?
Q6ZVZ8-1	1	yes
Q6ZVZ8-2	2

RefSeq proteins (1): NP_997721* (*=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 (13 total): repeat 6, sequence variant 4, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVZ8-F1	80.50	0.49

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: 25 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, OCT1_03, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_NEDDYLATION, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_CONJUGATION, AMEF2_Q6, chr2q37, GSE17721_PAM3CSK4_VS_CPG_16H_BMDC_UP, DESCARTES_MAIN_FETAL_SKELETAL_MUSCLE_CELLS, DESCARTES_FETAL_MUSCLE_SKELETAL_MUSCLE_CELLS, DESCARTES_FETAL_PLACENTA_STROMAL_CELLS, MYOCD_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), membrane (GO:0016020)

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
cellular anatomical structure	2
protein modification by small protein conjugation	1
intracellular anatomical structure	1
signal transduction	1
binding	1
cytoplasm	1

Protein interactions and networks

STRING

1004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB18	ASB17	Q8WXJ9	497
ASB18	ZDHHC2	Q9UIJ5	478
ASB18	DMRT2	Q9Y5R5	452
ASB18	NEDD4	P46934	428
ASB18	CCR10	P46092	398
ASB18	DMAC2L	Q99766	398
ASB18	CCDC13	Q8IYE1	384
ASB18	SPSB1	Q96BD6	376
ASB18	ATP5MC3	P48201	367
ASB18	ATP5PD	O75947	366
ASB18	LTBP2	Q14767	352
ASB18	AGAP1	Q9UPQ3	348
ASB18	CISH	Q9NSE2	329
ASB18	SLF1	Q9BQI6	325
ASB18	CUL5	Q93034	319

IntAct

0 interactions, top by confidence:

BioGRID (26): ASB18 (Affinity Capture-MS), ASB18 (Affinity Capture-MS), ASB18 (Affinity Capture-RNA), TCEB2 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), NME1 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), PGAM5 (Affinity Capture-MS), PRPS1 (Affinity Capture-MS), ERH (Affinity Capture-MS), SFPQ (Affinity Capture-MS), RPL15 (Affinity Capture-MS), AKR1B1 (Affinity Capture-MS), NONO (Affinity Capture-MS)

ESM2 similar proteins: A6NE02, A8MY62, C9JR72, D3Z7H8, D3ZU57, O09017, O15197, O19179, O95382, P0C0K6, P10588, P43136, P55203, Q02846, Q08DG4, Q15628, Q2KHV9, Q3U0S6, Q3UH93, Q5BK61, Q5U651, Q5W7P8, Q5ZMM1, Q6ZNJ1, Q6ZQA0, Q6ZVZ8, Q80ZD5, Q86WK7, Q8BH02, Q8BH83, Q8C828, Q8CIG9, Q8IUL8, Q8IYS2, Q8JGM4, Q8K2J9, Q8N239, Q8VHA6, Q91X21, Q96CD0

Diamond homologs: A0A0R4IQZ2, A5WVX9, B3DN87, B4E2M5, B8A4F0, C8VCL4, E1BLT8, E7F587, E7FH11, E9PTT0, E9QCD3, F1Q7H8, F1QAM1, F1QHM7, F1QX91, O60069, O74384, O80685, P14585, P42836, P59267, P59268, Q04629, Q0WQK2, Q10L01, Q21920, Q2T9W8, Q2TGI5, Q2TGJ4, Q2TGK3, Q2THW0, Q2THW8, Q2THX0, Q4I8B6, Q4IA62, Q4R690, Q4WZL8, Q500Z2, Q550R7, Q552M6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	93
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3242308	GRCh37/hg19 2q37.2-37.3(chr2:236478472-243048854)x1	Pathogenic

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
2:236196282:T:TA	donor_gain	1.0000
2:236196283:C:A	donor_gain	1.0000
2:236196297:T:TA	donor_gain	1.0000
2:236237954:GGCC:G	acceptor_loss	1.0000
2:236237955:GCC:G	acceptor_loss	1.0000
2:236237956:CCTGC:C	acceptor_loss	1.0000
2:236237957:C:A	acceptor_loss	1.0000
2:236237958:T:A	acceptor_loss	1.0000
2:236264136:GTTAC:G	donor_loss	1.0000
2:236264137:TTAC:T	donor_loss	1.0000
2:236264138:TACCT:T	donor_loss	1.0000
2:236264139:A:C	donor_loss	1.0000
2:236264140:C:CA	donor_loss	1.0000
2:236264144:G:C	donor_gain	1.0000
2:236214356:CCTTA:C	donor_loss	0.9900
2:236214357:CTTAC:C	donor_loss	0.9900
2:236214358:TTA:T	donor_loss	0.9900
2:236214359:TACC:T	donor_loss	0.9900
2:236214360:ACCT:A	donor_loss	0.9900
2:236237954:GGC:G	acceptor_gain	0.9900
2:236237957:C:CC	acceptor_gain	0.9900
2:236264135:GGTTA:G	donor_loss	0.9900
2:236195057:TC:T	acceptor_loss	0.9800
2:236195058:CT:C	acceptor_loss	0.9800
2:236195059:T:A	acceptor_loss	0.9800
2:236196955:C:CT	acceptor_gain	0.9800
2:236237952:GAGGC:G	acceptor_gain	0.9800
2:236237953:AGGC:A	acceptor_gain	0.9800
2:236237955:GC:G	acceptor_gain	0.9800
2:236237956:CC:C	acceptor_gain	0.9800

AlphaMissense

2985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:236237951:A:G	W112R	0.963
2:236237951:A:T	W112R	0.963
2:236194976:G:T	R433S	0.951
2:236195042:A:C	Y411D	0.948
2:236214751:A:C	Y238D	0.941
2:236237949:C:A	W112C	0.941
2:236237949:C:G	W112C	0.941
2:236241316:A:G	W98R	0.938
2:236241316:A:T	W98R	0.938
2:236214401:G:C	N354K	0.930
2:236214401:G:T	N354K	0.930
2:236196335:G:C	N384K	0.929
2:236196335:G:T	N384K	0.929
2:236237709:G:C	C192W	0.928
2:236214716:G:C	N249K	0.927
2:236214716:G:T	N249K	0.927
2:236194988:G:T	R429S	0.924
2:236214595:C:G	D290H	0.924
2:236214594:T:A	D290V	0.923
2:236237805:G:C	C160W	0.923
2:236237722:G:T	P188H	0.922
2:236264206:A:T	I47K	0.921
2:236194987:C:G	R429P	0.915
2:236195043:G:C	F410L	0.913
2:236195043:G:T	F410L	0.913
2:236195045:A:G	F410L	0.913
2:236237710:C:T	C192Y	0.911
2:236264287:A:G	L20S	0.911
2:236214576:G:T	P296Q	0.910
2:236237903:C:G	A128P	0.909

dbSNP variants (sampled 300 via entrez): RS1000062582 (2:236266403 A>G), RS1000084152 (2:236248976 T>A), RS1000102909 (2:236246652 C>G), RS1000119461 (2:236237293 GCGCCTC>G), RS1000160838 (2:236205524 A>G), RS1000172499 (2:236237056 G>A), RS1000179076 (2:236251138 T>A,G), RS1000195931 (2:236196020 G>A,T), RS1000219741 (2:236199164 C>A,T), RS1000291855 (2:236244321 T>C,G), RS1000314983 (2:236242842 G>A,T), RS1000344493 (2:236230336 T>C), RS1000495722 (2:236222494 G>A), RS1000559910 (2:236223139 C>A), RS1000613174 (2:236250809 C>T)

Disease associations

OMIM: gene MIM:621134 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000635_22	Response to statin therapy	2.000000e-07
GCST004361_2	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	2.000000e-06
GCST004361_5	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	3.000000e-06
GCST004412_3	Craniofacial microsomia	5.000000e-13
GCST90025872_2	Chronic widespread musculoskeletal pain	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007970	estrone measurement
EFO:0007972	androstenedione measurement
EFO:0010099	chronic widespread pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
propionaldehyde	decreases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	increases reaction, affects binding	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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