ASGR2

Chr 17

asialoglycoprotein receptor 2

Also known as: ASGP-R2, ASGPR2, CLEC4H2, HBXBP, HL-2

ASGR2 encodes the minor subunit of the asialoglycoprotein receptor, which mediates endocytosis and lysosomal degradation of glycoproteins with terminal galactose or N-acetylgalactosamine residues to maintain serum glycoprotein homeostasis. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), suggesting that mutations would likely cause severe disease, though no specific genetic disorders have been definitively associated with ASGR2 mutations in the provided information.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.53
Clinical SummaryASGR2
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
1.53LOEUF
pLI 0.000
Z-score 0.06
OE 0.98 (0.651.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.29Z-score
OE missense 0.94 (0.831.07)
176 obs / 187.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.98 (0.651.53)
00.351.4
Missense OE0.94 (0.831.07)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 14 / 14.2Missense obs/exp: 176 / 187.0Syn Z: 0.23
DN
0.7327th %ile
GOF
0.7027th %ile
LOF
0.3162th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

ASGR2 · 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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