ASB9

Chr X

ankyrin repeat and SOCS box containing 9

NCBI Gene: 140462 ENSG00000102048 UniProt: Q96DX5 OMIM: 300890

ASB9 encodes a substrate-recognition component of an E3 ubiquitin ligase complex that targets creatine kinases for proteasomal degradation. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy with developmental delay, seizures, and brain atrophy typically manifesting in infancy. The gene shows significant constraint against loss-of-function variants (LOEUF 0.58), suggesting intolerance to reduced protein levels.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ankyrin repeat and suppressor of cytokine signaling (SOCS) box protein family. Members of this family can interact with the elongin B-C adapter complex via their SOCS box domain and further complex with the cullin and ring box proteins to form E3 ubiquitin ligase complexes. They may function to mediate the substrate-recognition of the E3 ubiquitin ligases. A transcribed pseudogene of this gene has been identified on chromosome 15. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ASB9?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

255 rare PASS variants

Rare truncating (LoF)

1 in 4,300

17 rare PASS variants

Rare synonymous (reference)

1 in 420

108 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ASB9. 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 370	1 in 5,300
South Asian	~36k	1 in 230	≈ 1 in 35,000
Remaining (unassigned)	~31k	1 in 510	none seen
European (Finnish)	~27k	1 in 950	none seen
Admixed American	~23k	1 in 270	1 in 3,000
African / African American	~21k	1 in 290	1 in 2,800
East Asian	~20k	1 in 240	none seen
Ashkenazi Jewish	~13k	1 in 730	none seen
Middle Eastern	~2,758	1 in 550	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 ↓