ASB3

Chr 2

ankyrin repeat and SOCS box containing 3

Also known as: ASB-3

The ASB3 protein functions as a substrate-recognition component of an E3 ubiquitin ligase complex that targets specific proteins including TNFRSF1B, MAVS, and TRAF6 for proteasomal degradation, playing a role in regulating antiviral innate immunity. Mutations in ASB3 cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene shows tolerance to loss-of-function variation, consistent with a recessive inheritance pattern.

Summary from RefSeq, UniProt
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0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.90
LOEUF
GOF
Mechanism· predicted
Clinical SummaryASB3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.95
OE 0.58 (0.390.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.29Z-score
OE missense 1.05 (0.951.15)
314 obs / 299.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.390.90)
00.351.4
Missense OE1.05 (0.951.15)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 15 / 25.7Missense obs/exp: 314 / 299.8Syn Z: -1.59
DN
0.6066th %ile
GOF
0.6736th %ile
LOF
0.2677th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ASB3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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