WSB2

Chr 12AR

WD repeat and SOCS box containing 2

Also known as: LAGNS, SBA2

NCBI Gene: 55884 ENSG00000176871 UniProt: Q9NYS7 OMIM: 621524

The protein functions as a substrate-recognition component of an E3 ubiquitin ligase complex that targets specific proteins for degradation through the ubiquitin-proteasome system. Mutations cause Luo-Agrawal neurodevelopmental syndrome, which follows an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.361 OMIM phenotype

Clinical Summary— WSB2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 37 VUS of 64 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.36LOEUF

pLI 0.929

Z-score 3.72

OE 0.14 (0.06–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.14Z-score

OE missense 0.61 (0.53–0.70)

144 obs / 236.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.36)

0≤0.351.4

Missense OE?0.61 (0.53–0.70)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 3 / 21.7Missense obs/exp: 144 / 236.7Syn Z: -0.54

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS37

Likely Benign3

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	1	0	2
Likely Pathogenic	0	0	0	0	0
VUS	3	33	1	0	37
Likely Benign	0	1	0	2	3
Benign	0	1	0	2	3
Total	3	36	2	4	45

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap WSB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →