ASB2

protein-coding

ankyrin repeat and SOCS box containing 2, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

MANE transcript

NM_001202429.2

Inheritance

—

ClinVar variants

U:120B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr14:93,934,166-93,976,739

External References & Databases

Ensembl (ENSG00000100628)

Transcript & Mutation Effects

hg38 • Region Span ~42.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001202429.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			119 clinvar	6 clinvar		125
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	120	6	0	126

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 108 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001202429.2	RefSeq	NP_001189358.1	9	MANE Select
ENST00000555019.6	Ensembl	ENSP00000451575.1	9	MANE Select
NM_016150.5	RefSeq	NP_057234.2	8	Standard
ENST00000315988.8	Ensembl	ENSP00000320675.4	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
asb2b	Danio rerio	Structure: cardiac muscle cell Quality: shape abnormal

Gene / Model

Organism

Observed Phenotype

asb2b

Danio rerio

Structure: cardiac muscle cell

Quality: shape

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

signal transduction
protein ubiquitination
intracellular signal transduction
skeletal muscle cell differentiation
post-translational protein modification

Molecular Function

protein binding
ubiquitin protein ligase activity

Cellular Component

ubiquitin ligase complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000555019
Coding exons: 9
Length: 42639
Individuals with no LoFs: 125561
Homozygous LoFs: 0
Heterozygous LoFs: 187
Defined: 125748
p: 0.000744

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.391	391	413	0.946	0.0000257	4106
Missense (PolyPhen)		128	153.17	0.83566		1497
Synonymous	1.08	177	196	0.902	0.0000142	1299
Loss of Function	0.654	24	27.7	0.866	0.00000160	283

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0017	0.0016	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.0010	0.00097	rare
European (Non-Finnish)	0.00055	0.00054	rare
South Asian	0.00033	0.00033	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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. {ECO:0000269|PubMed:15590664, ECO:0000269|PubMed:16325183}.; FUNCTION: Isoform 2: Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA. {ECO:0000269|PubMed:19300455}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.687
RVIS EVS: -0.39
RVIS percentile EVS: 27.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.707

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium