ASGR1

Summary

ASGR1 (asialoglycoprotein receptor 1, HGNC:742) is a protein-coding gene on chromosome 17p13.1, encoding Asialoglycoprotein receptor 1 (P07306). Transmembrane protein predominantly expressed on hepatocytes that plays a key role in endocytosis of plasma glycoproteins that lack terminal sialic acid residues.

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 more abundant major subunit. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 432 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_001671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:742
Approved symbol	ASGR1
Name	asialoglycoprotein receptor 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	CLEC4H1
Ensembl gene	ENSG00000141505
Ensembl biotype	protein_coding
OMIM	108360
Entrez	432

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 36 protein_coding, 1 retained_intron

ENST00000269299, ENST00000380920, ENST00000570576, ENST00000572879, ENST00000573083, ENST00000573596, ENST00000574330, ENST00000574388, ENST00000619926, ENST00000863756, ENST00000863757, ENST00000863758, ENST00000863759, ENST00000863760, ENST00000863761, ENST00000863762, ENST00000863763, ENST00000863764, ENST00000863765, ENST00000863766, ENST00000863767, ENST00000863768, ENST00000863769, ENST00000863770, ENST00000863771, ENST00000863772, ENST00000863773, ENST00000863774, ENST00000863775, ENST00000863776, ENST00000863777, ENST00000863778, ENST00000863779, ENST00000863780, ENST00000863781, ENST00000863782, ENST00000863783

RefSeq mRNA: 2 — MANE Select: NM_001671 NM_001197216, NM_001671

CCDS: CCDS11089, CCDS56017

Canonical transcript exons

ENST00000269299 — 9 exons

Exon	Start	End
ENSE00000948984	7173961	7174067
ENSE00001296653	7178494	7178588
ENSE00001312224	7173431	7173833
ENSE00002891419	7174138	7174289
ENSE00003513332	7176981	7177076
ENSE00003574529	7177210	7177326
ENSE00003621536	7174374	7174460
ENSE00003672005	7176830	7176901
ENSE00003847583	7179190	7179370

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.62.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1592 / max 732.5895, expressed in 471 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164122	2.2261	64
164116	0.6502	205
164119	0.6175	353
164123	0.1986	23
164120	0.1046	23
164121	0.0971	20
164117	0.0797	35
164118	0.0764	40
164115	0.0446	19
164114	0.0381	14

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.62	gold quality
liver	UBERON:0002107	98.55	gold quality
monocyte	CL:0000576	94.72	gold quality
mononuclear cell	CL:0000842	93.84	gold quality
leukocyte	CL:0000738	93.28	gold quality
granulocyte	CL:0000094	91.05	gold quality
left testis	UBERON:0004533	86.40	gold quality
cerebellar hemisphere	UBERON:0002245	86.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.29	gold quality
cerebellar cortex	UBERON:0002129	86.17	gold quality
right testis	UBERON:0004534	85.77	gold quality
cortical plate	UBERON:0005343	85.64	gold quality
ganglionic eminence	UBERON:0004023	83.81	gold quality
cerebellum	UBERON:0002037	83.73	gold quality
testis	UBERON:0000473	83.05	gold quality
right frontal lobe	UBERON:0002810	82.55	gold quality
blood	UBERON:0000178	81.37	gold quality
cingulate cortex	UBERON:0003027	81.19	gold quality
anterior cingulate cortex	UBERON:0009835	81.06	gold quality
ventricular zone	UBERON:0003053	80.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.29	gold quality
prefrontal cortex	UBERON:0000451	79.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.33	silver quality
sperm	CL:0000019	77.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.72	gold quality
neocortex	UBERON:0001950	76.89	gold quality
frontal cortex	UBERON:0001870	76.02	gold quality
male germ cell	CL:0000015	75.62	gold quality
embryo	UBERON:0000922	75.10	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	58.55
E-CURD-112	yes	24.97
E-MTAB-5061	no	3.71
E-HCAD-31	no	2.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ASGR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-1256	95.44	66.33	784
HSA-MIR-6820-5P	94.04	61.13	161
HSA-MIR-4740-3P	91.27	64.89	113

Literature-anchored findings (GeneRIF, showing 33)

• The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-oligomeric receptor complexes (PMID:11943787)
• primary renal proximal tubular epithelial cells have a functional ASGPR, consisting of the H1 and H2 subunits, that is capable of specific ligand binding and uptake (PMID:12119473)
• Phosphorylation-dependent interaction with molecular chaperones (PMID:12167617)
• the effects of palmitoylation on ASGP-R activity and function (PMID:12359251)
• the spacing of a Cys residue relative to the TMD in the primary protein sequence of H1 is the major determinant for successful palmitoylation (PMID:12370180)
• Exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. (PMID:19520807)
• our findings suggest that both fibronectin and ASGPR mediate HBsAg binding to the cell surface, which provides further evidence for the potential roles of these two proteins in mediating HBV binding to liver cells. (PMID:20364278)
• Two naturally occurring ASGPR1 splice variants are produced in human hepatocytes. (PMID:20886072)
• Asialoglycoprotein receptor (ASGPR) interacted specifically and directly with the preS1 domain of HBV in vivo and in vitro. (PMID:21207081)
• found that the asialoglycoprotein receptor (ASGPR) is involved in hepatocyte recognition of cells predestined for killing, including activated autologous T lymphocytes (PMID:21656538)
• Constant sH2a levels suggest constitutive secretion from hepatocytes in healthy individuals; therefore, a decrease with cirrhosis suggests a diagnostic potential. (PMID:22219600)
• the cooperative binding mode of Ca(2+) makes it possible for ASGP-R to be more sensitive to Ca(2+) concentrations in early endosomes, and plays an important role in the efficient release of ligand from ASGP-R (PMID:22613667)
• the distribution of ASGR in human testis, was investigated. (PMID:23604802)
• The examined ASGPR1 expression levels by immunohistochemistry in HCC with different grades. Guidance for a targeting delivery strategy for anti-cancer drugs to HCC is suggested in this report. (PMID:23979840)
• Anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection. (PMID:24763545)
• Anti-ASGPR levels correlate with biochemical parameters and with the severity and manifestation autoimmune processes in patients with autoimmune hepatitis. (PMID:24933948)
• Flow cytometric assessment of ASGPR expression may be a useful predictor of liver dysfunction following major hepatectomy for HCC in Chinese patients. (PMID:25404440)
• Endocytic AMR controls TPO expression through Janus kinase 2 (JAK2) and the acute phase response signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro (PMID:25485912)
• findings show that the hepatitis E virus (HEV) ORF2 protein interacts directly with the ectodomain of both ASGR1 and ASGR2; ASGPR is involved in and facilitates HEV infection by binding to ORF2 (PMID:27155063)
• ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (PMID:27192541)
• This review will focus on the mechanisms of platelet senescence with specific emphasis on the role of post-translational modifications in platelet life-span and thrombopoietin production downstream of the hepatic Ashwell-Morrell receptor, originally termed asialoglycoprotein receptor (ASGPR). (PMID:27207430)
• ASGR1 can inhibit the activity of V-ATPase by interacting with LASS2, thereby suppressing the metastatic potential of hepatoma cells. (PMID:27241665)
• PEGylated lipoplexes were well tolerated by both HEK293 (ASGP-R-negative) and HepG2 (ASGP-R-positive) cell lines and delivered DNA to the hepatoma cell line HepG2 by ASGP-R mediation at levels three-fold greater than nonPEGylated lipoplexes. (PMID:28063265)
• Authors report the generation of a human embryonic stem cell line WAe001-A-6 harbouring homozygous ASGR1 mutations using CRISPR/Cas9. The mutation involves a 37bp deletion, resulting in a frame shift. (PMID:28952928)
• ASGR1 but not FOXM1 expression decreases in the peripheral blood mononuclear cells of diabetic atherosclerotic patients. (PMID:31202960)
• Our findings suggest that Clec10a in mice and Asgr1 in humans play an important role in skin homeostasis against inflammation associated with house dust mite-induced dermatitis. (PMID:31811054)
• Common gene variants in ASGR1 gene locus associate with reduced cardiovascular risk in absence of pleiotropic effects. (PMID:32679274)
• The Asialoglycoprotein Receptor Minor Subunit Gene Contributes to Pharmacokinetics of Factor VIII Concentrates in Hemophilia A. (PMID:34407556)
• Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans. (PMID:34762653)
• Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. (PMID:34837059)
• Novel SARS-CoV-2 receptors: ASGR1 and KREMEN1. (PMID:34903854)
• Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes. (PMID:38355848)
• Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress. (PMID:38459023)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asgr1	ENSMUSG00000020884
rattus_norvegicus	Asgr1	ENSRNOG00000018693
drosophila_melanogaster	tfc	FBGN0035199
drosophila_melanogaster	CG14866	FBGN0038315
drosophila_melanogaster	lectin-46Cb	FBGN0040092
drosophila_melanogaster	lectin-46Ca	FBGN0040093
drosophila_melanogaster	lectin-33A	FBGN0040096
drosophila_melanogaster	CG34033	FBGN0054033
caenorhabditis_elegans	clec-87	WBGENE00007709
caenorhabditis_elegans	clec-91	WBGENE00014117
caenorhabditis_elegans		WBGENE00016088
caenorhabditis_elegans		WBGENE00019606

Paralogs (14): CD209 (ENSG00000090659), FCER2 (ENSG00000104921), CLEC4M (ENSG00000104938), CLEC4A (ENSG00000111729), CD207 (ENSG00000116031), CLEC10A (ENSG00000132514), CLEC4F (ENSG00000152672), ASGR2 (ENSG00000161944), CLEC4E (ENSG00000166523), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC4C (ENSG00000198178), CLEC6A (ENSG00000205846)

Protein

Protein identifiers

Asialoglycoprotein receptor 1 — P07306 (reviewed: P07306)

Alternative names: C-type lectin domain family 4 member H1, Hepatic lectin H1

All UniProt accessions (7): P07306, I3L129, I3L1F8, I3L2S9, J3QSZ2, K7EPS5, Q6FGQ5

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane protein predominantly expressed on hepatocytes that plays a key role in endocytosis of plasma glycoproteins that lack terminal sialic acid residues. Specifically recognizes terminal galactose and N-acetylgalactosamine residues, facilitating the clearance of desialylated glycoproteins from circulation. Plays thereby a role in a variety of physiological processes, such as removal of desialylated platelets, elimination of activated lymphocytes and maintenance of serum glycoprotein homeostasis. Plays a role in the removal of desialylated platelets by activating a feedback loop regulating thrombopoietin (TPO) expression via the JAK2-STAT3 signaling pathway. Contributes also to recognition and elimination of activated lymphocytes by hepatocytes that can act as cytotoxic effectors. May also play a physiological role in the regulatory network of lipid homeostasis. Upon ligand binding, the receptor-ligand complex is internalized and trafficked to a sorting organelle, where dissociation occurs. The receptor is then recycled back to the cell surface. (Microbial infection) Plays an essential role in ACE2-independent SARS-CoV-2 entry by acting as alternate receptor.

Subunit / interactions. Interacts with LASS2. (Microbial infection) Interacts with hepatitis E virus capsid protein ORF2. (Microbial infection) Interacts with SARS-CoV-2 virus spike glycoprotein.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed exclusively in hepatic parenchymal cells.

Post-translational modifications. Phosphorylated on a cytoplasmic Ser residue. Palmitoylated at Cys-36. Palmitoylation is essential for coated pit-mediated endocytosis, dissociation, and delivery of ligand to lysosomes.

Miscellaneous. Calcium is required for ligand binding.

Isoforms (2)

UniProt ID	Names	Canonical?
P07306-1	H1a	yes
P07306-2	H1b, sASGPR

RefSeq proteins (2): NP_001184145, NP_001662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033989	CD209-like_CTLD	Domain
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059, PF03954

UniProt features (40 total): binding site 12, strand 7, disulfide bond 3, topological domain 2, modified residue 2, glycosylation site 2, helix 2, chain 1, transmembrane region 1, lipid moiety-binding region 1, splice variant 1, mutagenesis site 1, domain 1, region of interest 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9G76	X-RAY DIFFRACTION	1.2
6YAU	X-RAY DIFFRACTION	1.4
9G7E	X-RAY DIFFRACTION	1.4
9G7D	X-RAY DIFFRACTION	1.59
8TS0	X-RAY DIFFRACTION	1.7
5JQ1	X-RAY DIFFRACTION	1.83
5JPV	X-RAY DIFFRACTION	1.9
1DV8	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07306-F1	86.28	0.70

Antibody-complex structures (SAbDab): 1 — 8TS0

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 197; 216; 240; 242; 243; 253; 253; 254; 265; 266; 278; 191

Post-translational modifications (3): 16, 285, 36

Disulfide bonds (3): 154–165, 182–277, 255–269

Glycosylation sites (2): 79, 147

Mutagenesis-validated functional residues (1):

Position	Phenotype
36	complete loss of palmitoylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 131 (showing top): MODULE_45, MODULE_64, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, CEBPB_01, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, DELYS_THYROID_CANCER_DN, HSIAO_LIVER_SPECIFIC_GENES, MODULE_410, TGACATY_UNKNOWN, GNF2_HPX, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, MODULE_88, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS

GO Biological Process (3): receptor-mediated endocytosis (GO:0006898), immune response (GO:0006955), endocytosis (GO:0006897)

GO Molecular Function (8): asialoglycoprotein receptor activity (GO:0004873), D-mannose binding (GO:0005537), pattern recognition receptor activity (GO:0038187), identical protein binding (GO:0042802), fucose binding (GO:0042806), metal ion binding (GO:0046872), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monosaccharide binding	2
binding	2
cellular anatomical structure	2
endocytosis	1
immune system process	1
response to stimulus	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cargo receptor activity	1
signaling receptor activity	1
protein binding	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASGR1	ST3GAL4	Q11206	898
ASGR1	ASGR2	P07307	847
ASGR1	VWF	P04275	845
ASGR1	ST3GAL1	Q11201	798
ASGR1	CERS2	Q96G23	784
ASGR1	ATP1B2	P14415	749
ASGR1	ALB	P02768	727
ASGR1	PACC1	Q9H813	706
ASGR1	CLEC1B	Q9P126	697
ASGR1	MUC4	Q99102	677
ASGR1	SLC22A1	O15245	674
ASGR1	UGT1A1	P22309	649
ASGR1	ATP6V0C	P27449	649
ASGR1	KREMEN1	Q96MU8	649
ASGR1	FCAR	P24071	641

IntAct

100 interactions, top by confidence:

A	B	Type	Score
CERS2	ASGR1	psi-mi:“MI:0915”(physical association)	0.650
CERS2	ASGR1	psi-mi:“MI:0407”(direct interaction)	0.650
ASGR1	CERS2	psi-mi:“MI:0915”(physical association)	0.650
ASGR1	FCGR1A	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	IGFBP5	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	SPAG4	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	MCEMP1	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	AHNAK2	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	APH1A	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	HIBADH	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
NEMP1	ASGR1	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	ASGR1	psi-mi:“MI:0915”(physical association)	0.560
CLDN7	ASGR1	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	ASGR1	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	VSIR	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (67): ASGR1 (Two-hybrid), PLVAP (Affinity Capture-MS), PTPN2 (Affinity Capture-MS), ABAT (Affinity Capture-MS), ASGR1 (Two-hybrid), ASGR1 (Affinity Capture-MS), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid), ASGR1 (Two-hybrid)

ESM2 similar proteins: A4KWA1, O88200, O88201, P02706, P07306, P07307, P08290, P18519, P21854, P24721, P26951, P27471, P27812, P27814, P34927, P49300, P49301, P78380, P79391, Q0VCS6, Q2HXU8, Q3LUH2, Q3SXB8, Q49BZ4, Q5NKN2, Q5NKN4, Q5RBQ8, Q61190, Q6QLQ4, Q6UX15, Q6UXB4, Q8BNX1, Q8BWY2, Q8C1T8, Q8HZR8, Q8IUN9, Q8NC01, Q8VBX4, Q8VD98, Q8WTT0

Diamond homologs: A5PMY6, A6QP79, D3ZWT9, O14594, P02706, P02707, P05451, P06734, P07306, P07307, P07897, P07898, P08290, P08661, P10716, P10758, P11226, P13608, P13611, P16112, P19999, P20693, P22897, P24721, P34927, P41317, P43137, P48304, P49300, P49301, P55066, P55067, P60883, P70194, P81282, P82596, P86854, Q28343, Q28670, Q29011

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1109 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7173959:A:AC	donor_gain	1.0000
17:7173960:C:CC	donor_gain	1.0000
17:7174064:ATTT:A	acceptor_gain	1.0000
17:7174065:TTT:T	acceptor_gain	1.0000
17:7174066:TT:T	acceptor_gain	1.0000
17:7174067:TCTG:T	acceptor_loss	1.0000
17:7174068:C:A	acceptor_loss	1.0000
17:7174068:C:CC	acceptor_gain	1.0000
17:7174133:CTCAC:C	donor_loss	1.0000
17:7174134:TCA:T	donor_loss	1.0000
17:7174137:CCTG:C	donor_gain	1.0000
17:7174158:C:CT	donor_gain	1.0000
17:7174159:C:CT	donor_gain	1.0000
17:7174161:C:CT	donor_gain	1.0000
17:7174162:C:CT	donor_gain	1.0000
17:7174368:CCTTA:C	donor_loss	1.0000
17:7174369:CTTAC:C	donor_loss	1.0000
17:7174370:TTAC:T	donor_loss	1.0000
17:7174371:TACC:T	donor_loss	1.0000
17:7174372:A:AC	donor_gain	1.0000
17:7174372:A:C	donor_loss	1.0000
17:7174373:C:CC	donor_gain	1.0000
17:7174373:C:G	donor_loss	1.0000
17:7174457:TGAT:T	acceptor_gain	1.0000
17:7174458:GAT:G	acceptor_gain	1.0000
17:7174459:AT:A	acceptor_gain	1.0000
17:7174459:ATC:A	acceptor_loss	1.0000
17:7174460:TC:T	acceptor_loss	1.0000
17:7174461:C:CC	acceptor_gain	1.0000
17:7174461:CTGG:C	acceptor_loss	1.0000

AlphaMissense

1923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7173743:C:A	W264C	0.999
17:7173743:C:G	W264C	0.999
17:7173745:A:G	W264R	0.999
17:7173745:A:T	W264R	0.999
17:7173827:C:A	W236C	0.999
17:7173827:C:G	W236C	0.999
17:7173993:C:A	W223C	0.999
17:7173993:C:G	W223C	0.999
17:7174029:C:A	W211C	0.999
17:7174029:C:G	W211C	0.999
17:7173999:C:A	W221C	0.998
17:7173999:C:G	W221C	0.998
17:7174258:C:A	W158C	0.998
17:7174258:C:G	W158C	0.998
17:7173705:C:G	C277S	0.997
17:7173705:C:T	C277Y	0.997
17:7173706:A:T	C277S	0.997
17:7173771:C:G	C255S	0.997
17:7173772:A:T	C255S	0.997
17:7173829:A:G	W236R	0.997
17:7173829:A:T	W236R	0.997
17:7173995:A:G	W223R	0.997
17:7173995:A:T	W223R	0.997
17:7174186:G:C	C182W	0.997
17:7174187:C:G	C182S	0.997
17:7174187:C:T	C182Y	0.997
17:7174188:A:T	C182S	0.997
17:7174207:C:A	W175C	0.997
17:7174207:C:G	W175C	0.997
17:7173710:C:A	W275C	0.996

dbSNP variants (sampled 300 via entrez): RS1000115251 (17:7175199 TACAC>T), RS1000261475 (17:7175327 ACAC>A), RS1000993127 (17:7177537 C>G,T), RS1001066674 (17:7177742 T>C), RS1001329706 (17:7179309 G>A), RS1001403386 (17:7179561 T>C), RS1001530042 (17:7174510 G>A,C), RS1002591080 (17:7181324 T>G), RS1002968830 (17:7181128 G>A), RS1002982848 (17:7175945 AACAC>A,AAC), RS1003006678 (17:7181065 T>G), RS1003054502 (17:7176056 TCACA>T,TCA), RS1003080375 (17:7181286 C>A,T), RS1003111008 (17:7174639 A>T), RS1003510204 (17:7176008 A>G)

Disease associations

OMIM: gene MIM:108360 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001276_5	Liver enzyme levels (alkaline phosphatase)	8.000000e-12
GCST006016_37	Serum alkaline phosphatase levels	4.000000e-33
GCST007931_6	Medication use (HMG CoA reductase inhibitors)	3.000000e-10
GCST009652_5	Serum alkaline phosphatase levels	3.000000e-48
GCST010204_94	Low density lipoprotein cholesterol levels	7.000000e-37
GCST010243_191	Apolipoprotein B levels	1.000000e-33
GCST010245_136	LDL cholesterol levels	4.000000e-23
GCST011346_32	Total cholesterol levels	1.000000e-26
GCST011347_52	Low density lipoprotein cholesterol levels	5.000000e-31
GCST011353_24	Serum alkaline phosphatase levels	3.000000e-146
GCST011369_21	Iron status biomarkers (ferritin levels)	4.000000e-19
GCST90011900_152	Serum alkaline phosphatase levels	3.000000e-192
GCST90013406_3	Liver enzyme levels (alkaline phosphatase)	1.000000e-300

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004574	total cholesterol measurement
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2084 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

17 measured of 17 human assays (17 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-2,2-difluoroacetamide	KD	700 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-2,2,2-trifluoroacetamide	KD	1100 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-3,3,3-trifluoropropanamide	KD	1200 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(pentoxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	2180 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]propanamide	KD	2200 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(propoxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	3100 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-1-(butoxymethyl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	3300 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-1-(hexoxymethyl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	3400 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-1-(ethoxymethyl)-2,3-dihydroxy-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	5300 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxymethyl]-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	5500 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-N-methylacetamide	KD	6900 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]acetamide	KD	7180 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
(1S,2R,3R,4R,5R)-4-azido-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3-diol	KD	9000 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
tert-butyl N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-N-methylcarbamate	KD	12300 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]methanesulfonamide	KD	60000 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(1S,2R,3R,4R,5R)-2,3-dihydroxy-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-4-yl]-N-methylmethanesulfonamide	KD	110000 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR
N-[(2S,3R,4R,5R)-4,5-dihydroxy-6,6-bis(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	199000 nM	US-10376531: Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR

ChEMBL bioactivities

25 potent at pChembl≥5 of 29 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.16	Kd	700	nM	CHEMBL5894489
5.96	Kd	1100	nM	CHEMBL5780449
5.96	Kd	1100	nM	CHEMBL5894489
5.92	Kd	1200	nM	CHEMBL6003020
5.85	Kd	1400	nM	CHEMBL5780449
5.70	Kd	2000	nM	CHEMBL6003020
5.66	Kd	2180	nM	CHEMBL6010051
5.66	Kd	2200	nM	CHEMBL5856063
5.58	Kd	2600	nM	CHEMBL5879670
5.52	Kd	3000	nM	CHEMBL5846138
5.51	Kd	3100	nM	CHEMBL5846138
5.51	Kd	3100	nM	CHEMBL5856063
5.48	Kd	3300	nM	CHEMBL5949940
5.47	Kd	3400	nM	CHEMBL5879670
5.47	Kd	3400	nM	CHEMBL6010051
5.42	Kd	3800	nM	CHEMBL5978466
5.33	Kd	4700	nM	CHEMBL5949940
5.28	Kd	5300	nM	CHEMBL5978466
5.26	Kd	5500	nM	CHEMBL6024460
5.19	Kd	6500	nM	CHEMBL6024460
5.16	Kd	6900	nM	CHEMBL5750086
5.14	Kd	7180	nM	CHEMBL6049942
5.05	Kd	9000	nM	CHEMBL5790666

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Tunicamycin	increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
nickel sulfate	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
K 7174	decreases expression	1
GW 4064	decreases expression	1
belinostat	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042964	Binding	Inhibition of D-GalNAc-PAA binding to human recombinant ASGPR1 carbohydrate recognition domain expressed in Escherichia coli AD494 by competitive solid-phase binding assay	Design, synthesis and evaluation of monovalent ligands for the asialoglycoprotein receptor (ASGP-R). — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7KJ	Ubigene A-549 ASGR1 KO	Cancer cell line	Male
CVCL_LK60	WAe001-A-6	Embryonic stem cell	Male
CVCL_SD59	HAP1 ASGR1 (-) 1	Cancer cell line	Male
CVCL_SD60	HAP1 ASGR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.