ASB7

Chr 15

ankyrin repeat and SOCS box containing 7

NCBI Gene: 140460 ENSG00000183475 UniProt: Q9H672

ASB7 encodes a substrate-recognition component of an E3 ubiquitin ligase complex that targets specific proteins for degradation, regulating chromatin modifications and cell cycle progression. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.28), but no established Mendelian disorders have been definitively linked to ASB7 mutations in current clinical practice.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contains a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. In this way, SOCS box containing proteins may regulate protein turnover by targeting proteins for polyubiquination and, therefore, for proteasome-mediated degradation. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.28LOEUF

pLI 0.984

Z-score 3.59

OE 0.06 (0.02–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.27Z-score

OE missense 0.33 (0.27–0.41)

64 obs / 191.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.28)

0≤0.351.4

Missense OE?0.33 (0.27–0.41)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 1 / 17.0Missense obs/exp: 64 / 191.4Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in ASB7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 730

203 rare PASS variants

Rare truncating (LoF)

1 in 34,000

8 rare PASS variants

Rare synonymous (reference)

1 in 190

185 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ASB7. 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)	~556k	1 in 840	1 in 22,000
South Asian	~43k	1 in 1,300	none seen
Remaining (unassigned)	~30k	1 in 410	≈ 1 in 9,700
European (Finnish)	~27k	1 in 1,600	none seen
Admixed American	~22k	1 in 340	none seen
African / African American	~21k	1 in 400	none seen
East Asian	~20k	1 in 880	none seen
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	≈ 1 in 2,800	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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓