ASB11

Chr X

ankyrin repeat and SOCS box containing 11

NCBI Gene: 140456 ENSG00000165192 UniProt: Q8WXH4 OMIM: 300626

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.61

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in ASB11?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

315 rare PASS variants

Rare truncating (LoF)

1 in 1,000

54 rare PASS variants

Rare synonymous (reference)

1 in 450

125 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ASB11. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 170	1 in 1,300
South Asian	~36k	1 in 160	1 in 610
Remaining (unassigned)	~31k	1 in 120	1 in 750
European (Finnish)	~27k	1 in 1,000	1 in 2,800
Admixed American	~23k	1 in 130	1 in 1,000
African / African American	~21k	1 in 150	1 in 1,600
East Asian	~20k	1 in 210	1 in 3,300
Ashkenazi Jewish	~13k	1 in 850	1 in 890
Middle Eastern	~2,758	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓