ASGR2

Chr 17

asialoglycoprotein receptor 2

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

NCBI Gene: 433 ENSG00000161944 UniProt: P07307 OMIM: 108361

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a subunit of the asialoglycoprotein receptor. This receptor is a transmembrane protein that plays a critical role in serum glycoprotein homeostasis by mediating the endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues. The asialoglycoprotein receptor may facilitate hepatic infection by multiple viruses including hepatitis B, and is also a target for liver-specific drug delivery. The asialoglycoprotein receptor is a hetero-oligomeric protein composed of major and minor subunits, which are encoded by different genes. The protein encoded by this gene is the less abundant minor subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.53

Clinical Summary— ASGR2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.53LOEUF

pLI 0.000

Z-score 0.06

OE 0.98 (0.65–1.53)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.29Z-score

OE missense 0.94 (0.83–1.07)

176 obs / 187.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.98 (0.65–1.53)

0≤0.351.4

Missense OE?0.94 (0.83–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 14 / 14.2Missense obs/exp: 176 / 187.0Syn Z: 0.23

This gene — mechanism propensity

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.