WSB2

protein-coding

WD repeat and SOCS box containing 2, the group of WD repeat domain containing

Gene summary

This gene encodes a member of the WD-protein subfamily. The encoded protein contains five WD-repeats spanning most of the protein and an SOCS box in the C-terminus. The SOCS box may act as a bridge between specific substrate-binding domains and E3 ubiquitin protein ligases. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

MANE transcript

NM_018639.5

Inheritance

ClinVar variants

P:1U:46B:5

Top phenotype

Luo-Agrawal neurodevelopmental syndrome

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr12:118,032,687-118,062,430

External References & Databases

Ensembl (ENSG00000176871)

Transcript & Mutation Effects

hg38 • Region Span ~29.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WSB2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 9

Luo-Agrawal neurodevelopmental syndromeTotal: 3

WSB2-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018639.5. 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			5 clinvar	2 clinvar	1 clinvar	8
missense	1 clinvar		35 clinvar	1 clinvar	1 clinvar	38
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	46	3	2	52

Highest pathogenic variant AF is 0.00000342023

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018639.5	RefSeq	NP_061109.1	9	MANE Select
ENST00000315436.8	Ensembl	ENSP00000319474.3	9	MANE Select
NM_001278557.1	RefSeq	NP_001265486.1	9	Standard
NM_001278558.2	RefSeq	NP_001265487.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Neddylation

Biological Process

protein ubiquitination
intracellular signal transduction
post-translational protein modification

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315436
Coding exons: 9
Length: 29524
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125747
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	144	237	0.608	0.0000137	2636
Missense (PolyPhen)		25	82.329	0.30366		892
Synonymous	-0.541	109	102	1.07	0.00000671	801
Loss of Function	3.72	3	21.7	0.138	0.00000108	232

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. {ECO:0000250}.;

Recessive Scores

pRec: 0.0814

Intolerance Scores

LoFtool: 0.356
RVIS EVS: 0.22
RVIS percentile EVS: 68.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.757

Gene Damage Prediction

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