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…

LOEUF 0.58

Clinical Summary— ASB9

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.70) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

22 VUS of 96 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.696

Z-score 2.33

OE 0.12 (0.04–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.99Z-score

OE missense 0.74 (0.62–0.89)

84 obs / 113.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.58)

0≤0.351.4

Missense OE?0.74 (0.62–0.89)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 1 / 8.2Missense obs/exp: 84 / 113.5Syn Z: -0.29

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	21	22
Likely Benign	0	1	1
Benign	0	0	0
Total	1	22	23

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

View in ClinVar →

96 pathogenic / likely-pathogenic (of 104) ClinVar copy-number / structural variants overlap ASB9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →