ASB11

Chr X

ankyrin repeat and SOCS box containing 11

NCBI Gene: 140456 ENSG00000165192 UniProt: Q8WXH4

ASB11 encodes a substrate-recognition component of a cullin-5-RING E3 ubiquitin ligase complex that mediates proteasomal degradation of target proteins and regulates the endoplasmic reticulum unfolded protein response. Mutations cause autosomal recessive intellectual disability with developmental delay and seizures. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

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 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.61

Clinical Summary— ASB11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 VUS of 94 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.61LOEUF

pLI 0.000

Z-score 0.17

OE 0.94 (0.57–1.61)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.00Z-score

OE missense 1.00 (0.86–1.16)

127 obs / 126.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.94 (0.57–1.61)

0≤0.351.4

Missense OE?1.00 (0.86–1.16)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 9 / 9.6Missense obs/exp: 127 / 126.9Syn Z: -0.73

This gene — mechanism propensity

0.73top 25%

GOF

0.73top 25%

LOF

0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign4

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	40	0	1	42
Likely Benign	0	2	1	1	4
Benign	0	2	0	0	2
Total	1	44	1	2	48

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 106) ClinVar copy-number / structural variants overlap ASB11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →