ASGR2

Summary

ASGR2 (asialoglycoprotein receptor 2, HGNC:743) is a protein-coding gene on chromosome 17p13.1, encoding Asialoglycoprotein receptor 2 (P07307). Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed.

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.

Source: NCBI Gene 433 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 53 total — 1 pathogenic
• GTEx eGene: eQTL in 30 tissues, sQTL in 7 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.36 (unconstrained)
• MANE Select transcript: NM_001201352
• Notable: 53 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:743
Approved symbol	ASGR2
Name	asialoglycoprotein receptor 2
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	CLEC4H2
Ensembl gene	ENSG00000161944
Ensembl biotype	protein_coding
OMIM	108361
Entrez	433

Gene structure

Transcript identifiers

Ensembl transcripts: 106 — 91 protein_coding, 13 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000691900

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1, TSL 5: 1

ENST00000691900, ENST00000254850, ENST00000355035, ENST00000446679, ENST00000450034, ENST00000574868, ENST00000576487, ENST00000870979, ENST00000870980, ENST00000870981, ENST00000870982, ENST00000870983, ENST00000870984, ENST00000870985, ENST00000870986, ENST00000870987, ENST00000870988, ENST00000870989, ENST00000870990, ENST00000870991, ENST00000870992, ENST00000870993, ENST00000870994, ENST00000870995, ENST00000870996, ENST00000870997, ENST00000870998, ENST00000870999, ENST00000871000, ENST00000871001, ENST00000871002, ENST00000871003, ENST00000871004, ENST00000871005, ENST00000871006, ENST00000871007, ENST00000871008, ENST00000871009, ENST00000871010, ENST00000871011, ENST00000871012, ENST00000871013, ENST00000871014, ENST00000871015, ENST00000871016, ENST00000871017, ENST00000871018, ENST00000871019, ENST00000871020, ENST00000871021, ENST00000871022, ENST00000871023, ENST00000871024, ENST00000871025, ENST00000871026, ENST00000871027, ENST00000871028, ENST00000871029, ENST00000871030, ENST00000871031, ENST00000871032, ENST00000871033, ENST00000871034, ENST00000871035, ENST00000871036, ENST00000871037, ENST00000871038, ENST00000871039, ENST00000871040, ENST00000871041, ENST00000871042, ENST00000871043, ENST00000871044, ENST00000871045, ENST00000871046, ENST00000871047, ENST00000871048, ENST00000871049, ENST00000871050, ENST00000871051, ENST00000871052, ENST00000871053, ENST00000871054, ENST00000955571, ENST00001002750, ENST00001002751, ENST00001002753, ENST00001002754, ENST00001002757, ENST00001002760, ENST00001002761, ENST00001002763, ENST00001002766, ENST00001002767, ENST00001002769, ENST00001002770, ENST00001002771, ENST00001002773, ENST00001035967, ENST00001111557, ENST00001111558, ENST00001111559, ENST00001111560, ENST00001111561, ENST00001113566, ENST00001135252

RefSeq mRNA: 5 — MANE Select: NM_001201352 NM_001181, NM_001201352, NM_080912, NM_080913, NM_080914

CCDS: CCDS11088, CCDS32544, CCDS45598, CCDS92242

Canonical transcript exons

ENST00000691900 — 9 exons

Exon	Start	End
ENSE00000680346	7107836	7107907
ENSE00001801354	7114117	7114310
ENSE00003296001	7102090	7102196
ENSE00003354648	7107000	7107151
ENSE00003406452	7107231	7107317
ENSE00003527180	7108462	7108557
ENSE00003571955	7108772	7108888
ENSE00003926710	7114615	7114822
ENSE00003928890	7101326	7101740

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 99.45.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4069 / max 562.9304, expressed in 195 samples.

Highest expression (Bgee): lobe of liver, liver, monocyte, mononuclear cell, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASGR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	7.2e-66	-0.98	17:7108754:G:T
Liver	sqtl	1.4e-48	+1.22	17:7108754:G:T
Skin Sun Exposed Lower leg	eqtl	1.9e-29	-0.40	17:7136633:T:C
Whole Blood	eqtl	2.2e-27	+0.29	17:7111790:G:A
Skin Sun Exposed Lower leg	sqtl	2.5e-27	+0.72	17:7108758:C:T
Adipose Subcutaneous	eqtl	2.2e-24	+0.43	17:7112392:C:T
Skin Not Sun Exposed Suprapubic	eqtl	4.9e-17	-0.32	17:7136699:C:G
Skin Not Sun Exposed Suprapubic	sqtl	3.9e-15	+0.58	17:7108758:C:T
Esophagus Muscularis	eqtl	1.0e-13	+0.40	17:7108754:G:T
Nerve Tibial	eqtl	6.7e-13	+0.35	17:7112392:C:T
Lung	eqtl	1.1e-11	+0.34	17:7106107:C:T
Adipose Visceral Omentum	eqtl	1.1e-10	+0.29	17:7108758:C:T
Colon Transverse	eqtl	7.1e-10	+0.37	17:7112392:C:T
Esophagus Gastroesophageal Junction	eqtl	2.1e-09	-0.37	17:7112920:C:A
Thyroid	eqtl	2.8e-09	+0.34	17:7108754:G:T
Colon Sigmoid	eqtl	9.6e-09	+0.43	17:7108754:G:T
Artery Aorta	eqtl	1.1e-08	-0.31	17:7111957:C:T
Lung	sqtl	5.0e-08	+0.52	17:7108754:G:T
Esophagus Mucosa	eqtl	1.9e-07	+0.30	17:7111790:G:A
Artery Tibial	eqtl	1.6e-06	+0.25	17:7105815:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
164098	1.7157	68
164103	0.6817	104
164100	0.3440	32
164101	0.1725	64
164104	0.1554	59
164099	0.1253	17
164096	0.0755	26
164097	0.0735	13
164102	0.0635	36

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.45	gold quality
liver	UBERON:0002107	99.06	gold quality
monocyte	CL:0000576	95.10	gold quality
mononuclear cell	CL:0000842	95.07	gold quality
leukocyte	CL:0000738	95.02	gold quality
granulocyte	CL:0000094	94.83	gold quality
blood	UBERON:0000178	86.42	gold quality
gall bladder	UBERON:0002110	84.51	gold quality
triceps brachii	UBERON:0001509	81.67	gold quality
gluteal muscle	UBERON:0002000	81.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.48	gold quality
bone marrow	UBERON:0002371	74.98	gold quality
vermiform appendix	UBERON:0001154	74.89	gold quality
superficial temporal artery	UBERON:0001614	74.77	gold quality
spleen	UBERON:0002106	74.35	gold quality
caput epididymis	UBERON:0004358	73.98	gold quality
skin of leg	UBERON:0001511	73.92	gold quality
trabecular bone tissue	UBERON:0002483	73.22	silver quality
right lung	UBERON:0002167	72.55	gold quality
caecum	UBERON:0001153	72.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	71.75	gold quality
zone of skin	UBERON:0000014	71.64	gold quality
skin of abdomen	UBERON:0001416	71.21	gold quality
bone marrow cell	CL:0002092	71.12	silver quality
oocyte	CL:0000023	69.90	gold quality
gingival epithelium	UBERON:0001949	69.39	gold quality
vastus lateralis	UBERON:0001379	69.29	gold quality
type B pancreatic cell	CL:0000169	68.54	gold quality
quadriceps femoris	UBERON:0001377	68.50	gold quality
upper lobe of left lung	UBERON:0008952	68.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.87	gold quality
heart right ventricle	UBERON:0002080	67.51	gold quality
upper lobe of lung	UBERON:0008948	67.01	gold quality
mucosa of urinary bladder	UBERON:0001259	66.86	gold quality
tongue squamous epithelium	UBERON:0006919	66.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	66.45	gold quality
upper leg skin	UBERON:0004262	66.33	silver quality
biceps brachii	UBERON:0001507	66.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	66.10	gold quality
epithelial cell of pancreas	CL:0000083	66.05	gold quality
epithelium of esophagus	UBERON:0001976	66.01	gold quality
inferior olivary complex	UBERON:0002127	65.83	gold quality
gingiva	UBERON:0001828	65.68	gold quality
orbitofrontal cortex	UBERON:0004167	65.37	gold quality
esophagus squamous epithelium	UBERON:0006920	65.09	gold quality
corpus epididymis	UBERON:0004359	65.07	gold quality
cauda epididymis	UBERON:0004360	64.97	gold quality
periodontal ligament	UBERON:0008266	64.90	gold quality
endometrium epithelium	UBERON:0004811	64.83	gold quality
amniotic fluid	UBERON:0000173	64.63	gold quality
squamous epithelium	UBERON:0006914	64.63	gold quality
mammalian vulva	UBERON:0000997	64.15	gold quality
middle temporal gyrus	UBERON:0002771	63.86	gold quality
right coronary artery	UBERON:0001625	63.80	gold quality
adipose tissue of abdominal region	UBERON:0007808	63.56	gold quality
omental fat pad	UBERON:0010414	63.54	gold quality
peritoneum	UBERON:0002358	63.52	gold quality
upper arm skin	UBERON:0004263	63.36	gold quality
nephron tubule	UBERON:0001231	63.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	63.19	gold quality
layer of synovial tissue	UBERON:0007616	63.15	gold quality
kidney epithelium	UBERON:0004819	63.14	gold quality
germinal epithelium of ovary	UBERON:0001304	63.07	gold quality
olfactory bulb	UBERON:0002264	63.03	gold quality
renal glomerulus	UBERON:0000074	62.40	gold quality
prefrontal cortex	UBERON:0000451	62.39	gold quality
metanephric glomerulus	UBERON:0004736	62.27	gold quality
right frontal lobe	UBERON:0002810	62.25	gold quality
kidney	UBERON:0002113	62.21	gold quality
tibia	UBERON:0000979	62.13	silver quality
metanephros	UBERON:0000081	62.10	gold quality
epithelium of nasopharynx	UBERON:0001951	62.07	gold quality
frontal cortex	UBERON:0001870	61.89	gold quality
nasal cavity epithelium	UBERON:0005384	61.88	gold quality
adult mammalian kidney	UBERON:0000082	61.80	gold quality
choroid plexus epithelium	UBERON:0003911	61.76	gold quality
lymph node	UBERON:0000029	61.68	gold quality
thymus	UBERON:0002370	61.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.37	gold quality
placenta	UBERON:0001987	61.34	gold quality
vena cava	UBERON:0004087	61.25	gold quality
muscle tissue	UBERON:0002385	61.06	gold quality
deltoid	UBERON:0001476	61.03	gold quality
nipple	UBERON:0002030	60.93	gold quality
adipose tissue	UBERON:0001013	60.79	gold quality
body of tongue	UBERON:0011876	60.68	gold quality
epithelium of bronchus	UBERON:0002031	60.60	gold quality
mucosa of transverse colon	UBERON:0004991	60.55	gold quality
neocortex	UBERON:0001950	60.51	gold quality
bronchus	UBERON:0002185	60.51	gold quality
connective tissue	UBERON:0002384	60.45	gold quality
tongue	UBERON:0001723	60.44	gold quality
medulla oblongata	UBERON:0001896	60.37	gold quality
lung	UBERON:0002048	60.36	gold quality
secondary oocyte	CL:0000655	60.22	gold quality
left uterine tube	UBERON:0001303	60.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	60.07	gold quality
cardia of stomach	UBERON:0001162	60.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.36

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 64 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	559.0	medium
Gallbladder	tissue	16.3	not detected
Appendix	tissue	7.4	not detected
Bone marrow	tissue	6.6	not detected
Skin 1	tissue	4.9	not detected
Spleen	tissue	2.0	not detected
Urinary bladder	tissue	1.8	not detected
Choroid plexus	tissue	1.5
Superior colliculi	tissue	1.4
Smooth muscle	tissue	1.2	not detected
Adipose tissue	tissue	1.1	not detected
Kidney	tissue	1.1	not detected
Tonsil	tissue	1.0	not detected
Lymph node	tissue	0.8	not detected
Lung	tissue	0.8	not detected
Locus coeruleus	tissue	0.7
Postcentral gyrus	tissue	0.7
Stomach 1	tissue	0.5	not detected
Colon	tissue	0.5	not detected
Pancreas	tissue	0.5	not detected
Nucleus accumbens	tissue	0.5
Placenta	tissue	0.5	not detected
Small intestine	tissue	0.5	not detected
Hippocampus	tissue	0.5	not detected
Thymus	tissue	0.5
Olfactory bulb	tissue	0.5
Cervix	tissue	0.4	not detected
Breast	tissue	0.4	not detected
Testis	tissue	0.4	not detected
Salivary gland	tissue	0.4	not detected
Rectum	tissue	0.4	not detected
Ovary	tissue	0.3	not detected
Vagina	tissue	0.3	not detected
Esophagus	tissue	0.3	not detected
Endometrium 1	tissue	0.3	not detected
Duodenum	tissue	0.3	not detected
Pituitary gland	tissue	0.2
Heart muscle	tissue	0.2	not detected
Cerebral cortex	tissue	0.2	not detected
Seminal vesicle	tissue	0.2	not detected
Skeletal muscle	tissue	0.2	not detected
Motor cortex	tissue	0.2
Prostate	tissue	0.2	not detected
Adrenal gland	tissue	0.2	not detected
Hippocampal formation	tissue	0.2
Entorhinal cortex	tissue	0.2
Prefrontal cortex	tissue	0.1
Parathyroid gland	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Tongue	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Substantia nigra	tissue	0.1
Thyroid gland	tissue	0.1	not detected
Spinal cord	tissue	0.1
Ventral forebrain	tissue	0.1
Retrosplenial and cingulate cortex	tissue	0.1
Fallopian tube	tissue	0.1	not detected
Septum	tissue	0.1
Caudate putamen	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Anterior thalamic nucleus, ventral (1.8), Precentral gyrus (1.5), Dorsolateral tegmental area (1.4), Lateral funiculus (white matter) (1.3), Frontal operculum (1.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASGR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-122-3P	94.51	65.61	75
HSA-MIR-6761-3P	77.17	65.96	50

Functional genomics

gnomAD constraint: pLI 7.78e-13, LOEUF 1.36, missense Z 0.287 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000691900 — one region, missense o/e 1.00.

Literature-anchored findings (GeneRIF, showing 10)

• 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)
• trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid (PMID:12089159)
• 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)
• Exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. (PMID:19520807)
• found that the asialoglycoprotein receptor (ASGPR) is involved in hepatocyte recognition of cells predestined for killing, including activated autologous T lymphocytes (PMID:21656538)
• sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function. (PMID:22096539)
• the distribution of ASGR in human testis, was investigated. (PMID:23604802)
• 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)
• 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)
• Although gastric cancer cell-invasive activity was significantly decreased by knockdown, forced expression of ASGR2 promoted invasive activity. (PMID:29784667)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asgr2	ENSMUSG00000040963
rattus_norvegicus	Asgr2	ENSRNOG00000030726
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), ASGR1 (ENSG00000141505), CLEC4F (ENSG00000152672), CLEC4E (ENSG00000166523), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC4C (ENSG00000198178), CLEC6A (ENSG00000205846)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88082) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal homeostasis	2
increased susceptibility to bacterial infection	1
increased susceptibility to induced morbidity/mortality	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q66S50	100.0%	Diamond
Papio papio	Q66S65	100.0%	Diamond
Nomascus concolor	Q66S58	99.2%	Diamond
Pongo abelii	Q5RBQ8	98.3%	Diamond
Chlorocebus aethiops	Q66S37	98.0%	Diamond
Trachypithecus obscurus	Q66S41	98.0%	Diamond
Bos taurus	Q6RXL1	96.0%	Diamond
Ovis aries	Q9TT06	96.0%	Diamond
Macaca mulatta	Q1PBC5	94.4%	Diamond
Oryctolagus cuniculus	P12842	83.9%	Diamond
Equus caballus	Q95L88	82.7%	Diamond
Gallus gallus	Q2LK54	80.9%	Diamond
Sus scrofa	Q9TTK7	78.8%	Diamond
Danio rerio	A5PMY6	57.5%	Diamond
Periplaneta americana	P26305	47.8%	Diamond
Patiria pectinifera	Q8WPD0	44.1%	Diamond
Mytilus galloprovincialis	P86854	39.7%	Diamond
Fowlpox virus strain NVSL	P14371	47.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLC16A11	protein-coding	162515
SLC16A13	protein-coding	201232
CLEC10A	protein-coding	10462
BCL6B	protein-coding	255877
ASGR1	protein-coding	432

Protein

Protein identifiers

Asialoglycoprotein receptor 2 — P07307 (reviewed: P07307)

Alternative names: C-type lectin domain family 4 member H2, Hepatic lectin H2

All UniProt accessions (4): B4E1D2, P07307, I3L1H2, Q7Z4G9

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.

Subunit / interactions. The functioning ligand-binding unit of this receptor is thought to be at least a dimer. Interacts with LASS2. (Microbial infection) Interacts with hepatitis E virus capsid protein ORF2.

Subcellular location. Membrane.

Tissue specificity. Expressed exclusively in hepatic parenchymal cells.

Miscellaneous. Calcium is required for ligand binding.

Isoforms (3)

UniProt ID	Names	Canonical?
P07307-1	1	yes
P07307-2	2
P07307-3	3

RefSeq proteins (5): NP_001172, NP_001188281, NP_550434, NP_550435, NP_550436 (=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 (26 total): strand 6, glycosylation site 3, disulfide bond 3, topological domain 2, splice variant 2, helix 2, chain 1, sequence variant 1, transmembrane region 1, domain 1, region of interest 1, short sequence motif 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8URF	Crystal Structure of human ASGR2 CRD (Carbohydrate Recognition Domain) bound to 8G8 Fab	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07307-F1	79.50	0.47

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 8URF

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endoplasmic reticulum; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Post-translational modifications (2)

Type	Positions
Phosphoserine	13
S-palmitoyl cysteine	54

Disulfide bonds (3)

Type	Positions
Disulfide bond	177–188, 205–300, 278–292

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	170, 305, 102

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

MSigDB gene sets: 154 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GNF2_GSTM1, MODULE_64, GNF2_HPN, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, COUP_01, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, MODULE_410, GNF2_HPX, MODULE_88, MODULE_113

GO Biological Process (4): endocytosis (GO:0006897), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), bone mineralization (GO:0030282)

GO Molecular Function (6): asialoglycoprotein receptor activity (GO:0004873), D-mannose binding (GO:0005537), pattern recognition receptor activity (GO:0038187), fucose binding (GO:0042806), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (5): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endoplasmic reticulum quality control compartment (GO:0044322), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

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

GO top-level categories

21 GO namespaces:

Category	Terms
cellular anatomical structure	3
monosaccharide binding	2
binding	2
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
immune system process	1
response to stimulus	1
signal transduction	1
ossification	1
biomineral tissue development	1
animal gross anatomical part developmental process	1
cargo receptor activity	1
signaling receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endoplasmic reticulum	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
endoplasmic reticulum quality control compartment	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 533 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASGR2	ST3GAL4	Q11206	932
ASGR2	CERS2	Q96G23	765
ASGR2	ST3GAL1	Q11201	761
ASGR2	VWF	P04275	725
ASGR2	ATP6V0C	P27449	721
ASGR2	SLC22A1	O15245	678
ASGR2	SAAL1	Q96ER3	462
ASGR2	CCDC85C	A6NKD9	434
ASGR2	VWCE	Q96DN2	433
ASGR2	ST6GAL1	P15907	419
ASGR2	RNASEK	Q6P5S7	416
ASGR2	CSN1S1	P47710	380
ASGR2	SAA4	P35542	354
ASGR2	ADPGK	Q9BRR6	342
ASGR2	LDLR	P01130	312

IntAct

Human interaction partners of ASGR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
CERS2	physical association	0.650	3
MT-CO1	association	0.530	2
GLUD1	physical association	0.370	1
HES1	physical association	0.370	1
ACSL4	association	0.350	1
RPS7	association	0.350	1
SCAMP2	association	0.350	1

BioGRID (128 interactions; top human partners by supporting records): COX1 (Affinity Capture-MS; 3 records), FKRP (Affinity Capture-MS; 3 records), JMJD8 (Affinity Capture-MS; 3 records), LMAN2L (Affinity Capture-MS; 3 records), MFSD8 (Affinity Capture-MS; 3 records), PARVG (Affinity Capture-MS; 3 records), RPL23 (Affinity Capture-MS; 3 records), SERINC1 (Affinity Capture-MS; 3 records), SLC38A9 (Affinity Capture-MS; 3 records), SOAT1 (Affinity Capture-MS; 3 records), TIMP3 (Affinity Capture-MS; 3 records), TMEM214 (Affinity Capture-MS; 3 records), TMPPE (Affinity Capture-MS; 3 records), TTYH3 (Affinity Capture-MS; 3 records), CERS2 (Reconstituted Complex; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ASGR1-ASGR2 receptor complex	2	ASGR1, ASGR2

Disease & clinical

Genetic variants

Variant evidence for ASGR2: 53 ClinVar records (1 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2498727	GRCh37/hg19 17p13.1(chr17:7004894-7766789)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ASGR2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 1,075):

Position(s)	Effect	Δscore	Sites
17:7106998–7106999	donor_loss	1.0000	5
17:7107152–7107153	acceptor_loss	1.0000	4
17:7102088–7102089	donor_loss	0.9900	5
17:7102197–7102198	acceptor_loss	0.9900	3
17:7107152–7107153	acceptor_loss	0.9900	2
17:7107229–7107230	donor_loss	0.9900	6
17:7101741–7101742	acceptor_loss	0.9800	5
17:7102197–7102198	acceptor_loss	0.9800	3
17:7107834–7107835	donor_loss	0.9800	5
17:7108460–7108461	donor_loss	0.9800	6

AlphaMissense

340 missense substitutions predicted likely pathogenic (of 2,044 scored), across 89 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C205	7	0.980	0.991
C300	7	0.965	0.986
W246	7	0.964	0.996
W259	7	0.962	0.996
W287	7	0.961	0.995
C278	7	0.960	0.982
W234	7	0.946	0.989
C188	7	0.944	0.964
C292	7	0.938	0.968
W181	7	0.919	0.993
W298	7	0.917	0.984
F223	7	0.913	0.977
W244	7	0.898	0.980
C177	7	0.896	0.936
F191	7	0.891	0.977
W198	7	0.880	0.985
D289	7	0.863	0.898
D248	7	0.861	0.924
D265	7	0.816	0.874
C162	7	0.773	0.835

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (validation)	favorable	0.000127
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.00069

Disease associations

OMIM: gene MIM:108361 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST006614_51	Total cholesterol levels	6e-22
GCST90013406_67	Liver enzyme levels (alkaline phosphatase)	7e-15
GCST004721_3	Congenital heart disease (maternal effect)	2e-6
GCST010396_7	Gut microbiota (bacterial taxa, hurdle binary method)	7e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, decreases methylation	2
Nickel	increases expression	2
propionaldehyde	decreases expression	1
deoxynivalenol	decreases expression	1
titanium dioxide	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
K 7174	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
gardiquimod	decreases expression, decreases reaction	1
Rosiglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	increases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Ozone	increases expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	affects expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.