LGALS8

Summary

LGALS8 (galectin 8, HGNC:6569) is a protein-coding gene on chromosome 1q43, encoding Galectin-8 (O00214). Beta-galactoside-binding lectin that acts as a sensor of membrane damage caused by infection and restricts the proliferation of infecting pathogens by targeting them for autophagy.

This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 3964 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total — 1 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_201544

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6569
Approved symbol	LGALS8
Name	galectin 8
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	PCTA-1
Ensembl gene	ENSG00000116977
Ensembl biotype	protein_coding
OMIM	606099
Entrez	3964

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 38 protein_coding, 10 retained_intron, 2 nonsense_mediated_decay

ENST00000238181, ENST00000323938, ENST00000341872, ENST00000352231, ENST00000366583, ENST00000366584, ENST00000406509, ENST00000416919, ENST00000430527, ENST00000434231, ENST00000442397, ENST00000450372, ENST00000454943, ENST00000475670, ENST00000481485, ENST00000489586, ENST00000525042, ENST00000525789, ENST00000526589, ENST00000526634, ENST00000526652, ENST00000527974, ENST00000528259, ENST00000528782, ENST00000529489, ENST00000529796, ENST00000532640, ENST00000532826, ENST00000891071, ENST00000891072, ENST00000891073, ENST00000891074, ENST00000891075, ENST00000891076, ENST00000891077, ENST00000891078, ENST00000891079, ENST00000891080, ENST00000891081, ENST00000891082, ENST00000891083, ENST00000891084, ENST00000918759, ENST00000918760, ENST00000968020, ENST00000968021, ENST00000968022, ENST00000968023, ENST00000968024, ENST00000968025

RefSeq mRNA: 4 — MANE Select: NM_201544 NM_006499, NM_201543, NM_201544, NM_201545

CCDS: CCDS1611, CCDS1612

Canonical transcript exons

ENST00000366584 — 10 exons

Exon	Start	End
ENSE00001381502	236523982	236524061
ENSE00001865851	236548012	236552981
ENSE00003491296	236543560	236543648
ENSE00003551645	236544750	236544915
ENSE00003563486	236525968	236526115
ENSE00003626684	236540564	236540683
ENSE00003627786	236538879	236539089
ENSE00003646448	236542761	236542787
ENSE00003657852	236541654	236541710
ENSE00003687068	236537497	236537585

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.4290 / max 566.9452, expressed in 1795 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9241	41.5337	1791
9240	0.7316	437
9242	0.7284	379
9237	0.4287	190
9239	0.3272	147
9238	0.3068	150
9236	0.2123	77
9235	0.0622	27
9234	0.0510	9
9243	0.0405	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.34	gold quality
male germ cell	CL:0000015	97.11	gold quality
germinal epithelium of ovary	UBERON:0001304	96.75	gold quality
monocyte	CL:0000576	96.14	gold quality
gall bladder	UBERON:0002110	95.82	gold quality
mononuclear cell	CL:0000842	95.65	gold quality
skin of abdomen	UBERON:0001416	95.64	gold quality
skin of leg	UBERON:0001511	95.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.52	gold quality
left testis	UBERON:0004533	95.50	gold quality
renal glomerulus	UBERON:0000074	95.49	gold quality
spleen	UBERON:0002106	95.49	gold quality
right testis	UBERON:0004534	95.48	gold quality
leukocyte	CL:0000738	95.43	gold quality
body of pancreas	UBERON:0001150	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.37	gold quality
metanephric glomerulus	UBERON:0004736	95.36	gold quality
minor salivary gland	UBERON:0001830	95.29	gold quality
right uterine tube	UBERON:0001302	95.23	gold quality
left ovary	UBERON:0002119	95.20	gold quality
adrenal tissue	UBERON:0018303	95.04	gold quality
right lung	UBERON:0002167	95.01	gold quality
rectum	UBERON:0001052	94.93	gold quality
zone of skin	UBERON:0000014	94.91	gold quality
omental fat pad	UBERON:0010414	94.88	gold quality
peritoneum	UBERON:0002358	94.86	gold quality
right ovary	UBERON:0002118	94.83	gold quality
secondary oocyte	CL:0000655	94.69	gold quality
pancreas	UBERON:0001264	94.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CD28, CREB1, ESR1

miRNA regulators (miRDB)

141 targeting LGALS8, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• The binding ability of galectin-8 to membrane-associated GM3 was confirmed using CHO cells, which predominantly express GM3 (PMID:12851289)
• Human galectin-8 induced firm and reversible adhesion of peripheral blood neutrophils but not eosinophils to a plastic surface in a lactose-sensitive manner; galectin-8 is a novel factor that modulates the neutrophil function. (PMID:12881409)
• REVIEW: isoforms and role in neoplastic transformation/cancer (PMID:14758080)
• galectin-8 is a modulator of cellular growth through up-regulation of p21 (PMID:15753078)
• Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta1 integrins and to trigger signaling pathways conducive to cell spreading. (PMID:16368432)
• The affinity of Gal-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface is explored. (PMID:17339281)
• galectin-8 sorting is based on carbohydrate fine specificity (PMID:17580315)
• The function of galectin-8 in Jurkat T-cells, is analysed. (PMID:18024965)
• allows Gal-8 to signal phosphatidylserine exposure in leukocytes entirely through C-terminal domain recognition of polyLacNAc glycans (PMID:18456665)
• chemical analysis of talose-selectivity of galectin-4 and galectin-8 (PMID:18539029)
• Gal8 modulates trabecular meshwork cell adhesion and spreading, at least in part, by interacting with alpha2-3-sialylated glycans on beta(1) integrins. (PMID:18849583)
• Galectin-8 was expressed in the majority of papillary carcinomas. Positive but weaker staining was found in some of follicular thyroid carcinomas and adenomas. Galectin-8 found in hyperplastic areas adjacent to tumor was weakly positive in 9 of 31 cases. (PMID:19009371)
• These data suggest a role for galectin-8 and podoplanin in supporting the connection of the lymphatic endothelium to the surrounding extracellular matrix, most likely in cooperation with other glycoproteins on the surface of lymphatic endothelial cells. (PMID:19268462)
• The glycan-binding proteins of the galectin family can modulate the immune system. Anti-galectin autoantibodies thus could have functional and/or pathogenic implications in inflammatory processes and autoimmunity. (PMID:19395456)
• crystal of a protease-resistant mutant form of human galectin-8 was obtained using the hanging-drop method and was found to belong to the tetragonal space group P4(3)2(1)2 (PMID:19407390)
• Galectin-8 up-regulation is associated with hypopharyngeal and laryngeal tumor progression. (PMID:20044599)
• Platelets not only contain Gal-8, but also expose Gal-8 after thrombin activation. Findings reveal Gal-8 isoforms as a potent platelet activator; immobilized Gal-8 promotes platelet adhesion/spreading. (PMID:20858220)
• Studies indicated that Gal-8 was expressed both in the cytoplasm and nucleus in ECs of normal and tumor vessels. (PMID:20876211)
• Galectin-8-N-domain recognition mechanism for sialylated and sulfated glycans. (PMID:21288902)
• galectin-8 loss might be an early step in the development of malignant lesions of the bladder and is a significant independent predictor of recurrence (PMID:21757871)
• Gal-8 was expressed by villous and extravillous cytotrophoblast. (PMID:21862124)
• Galectin 1 and galectin 8 promote influenza virus binding in dose dependent manner. (PMID:22022970)
• This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease. (PMID:22173878)
• Glycoproteomic identification of galectin-3 and -8 ligands in bronchoalveolar lavage of mild asthmatics and healthy subjects. (PMID:22240167)
• results illustrate how cells deploy the danger receptor galectin 8 to combat infection by monitoring endosomal and lysosomal integrity on the basis of the specific lack of complex carbohydrates in the cytosol (PMID:22246324)
• a novel role for the tandem repeat Gal8 in promoting FV endocytosis. (PMID:22267735)
• The galectin-binding ability of a glycoprotein is not only a promising biomarker candidate but may also have a specific function when the glycoprotein encounters the galectin in tissue cells, and be related to the pathophysiological state of the patient. (PMID:22285770)
• Association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population. (PMID:22683700)
• Results indicate a difference in specificity between N-terminal and C-terminal carbohydrate recognition domains (N-CRD and C-CRD) of galectin-8. (PMID:22913484)
• Galectin-8 promotes cytoskeletal rearrangement in trabecular meshwork cells through activation of Rho signaling. (PMID:22973445)
• Data indicate that the binding site in galectin-8 is essential for the recruitment of the autophagy receptor NDP52 to cytosol-exposed Salmonella Typhimurium. (PMID:23386746)
• analysis of how human Galectin-8C domain interacts with its glycan ligands (PMID:23555773)
• Focusing on the F19Y change in galectin-8, we study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. (PMID:24418318)
• We integrate here the available information on Gal-8 expression in different tumor types and attempt to elucidate associations of its expression and localization with tumor progression[review] (PMID:24696431)
• Whereas Galectin (Gal)-1, -3, and -8 triggered vascular endothelial growth factor (VEGF) release, only Gal-8 induced endostatin secretion. (PMID:24788652)
• The implications of gal-8 in tumor angiogenesis remain to be further explored, but it is exciting to speculate that modulating gal-8-glycan interactions could be used to block lymphatic-vascular connections vital for metastasis (PMID:24939370)
• these results not only confirm the pro-inflammatory role we have already proposed for Gal-8 in other cellular systems but also suggest that this lectin is orchestrating the interaction between leukocytes, platelets and endothelial cells (PMID:24957054)
• Gal-8 expression is a potential independent unfavorable prognostic indicator for postoperative recurrence of patients with localized pT1 clear cell renal cell carcinoma (PMID:25499921)
• The fundamental roles of galectin-8 in human anaplastic large cell lymphoma (PMID:25573487)
• Platelet-derived factor V/Va is generated following endocytosis of the plasma-derived molecule by the platelet precursor cells, megakaryocytes, via a two receptor system consisting of LRP-1 and an unidentified specific “binding site”. (PMID:25800007)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	lgals8a	ENSDARG00000037066
danio_rerio	lgals8b	ENSDARG00000037613
mus_musculus	Lgals8	ENSMUSG00000057554
rattus_norvegicus	Lgals8	ENSRNOG00000018046
caenorhabditis_elegans		WBGENE00002264
caenorhabditis_elegans		WBGENE00002266
caenorhabditis_elegans		WBGENE00002269
caenorhabditis_elegans		WBGENE00002270
caenorhabditis_elegans		WBGENE00002271
caenorhabditis_elegans		WBGENE00004165
caenorhabditis_elegans		WBGENE00018255

Paralogs (16): LGALS14 (ENSG00000006659), LGALS2 (ENSG00000100079), LGALS1 (ENSG00000100097), LGALS13 (ENSG00000105198), CLC (ENSG00000105205), LGALSL (ENSG00000119862), LGALS3 (ENSG00000131981), LGALS12 (ENSG00000133317), LGALS9 (ENSG00000168961), LGALS9B (ENSG00000170298), LGALS4 (ENSG00000171747), LGALS9C (ENSG00000171916), LGALS7B (ENSG00000178934), LGALS7 (ENSG00000205076), LGALS16 (ENSG00000249861), GRIFIN (ENSG00000275572)

Protein

Protein identifiers

Galectin-8 — O00214 (reviewed: O00214)

Alternative names: Po66 carbohydrate-binding protein, Prostate carcinoma tumor antigen 1

All UniProt accessions (11): O00214, B1ANM0, E9PJ77, E9PN19, E9PNC2, E9PPL1, E9PPM4, E9PRN3, F6V2D4, H7BXD8, Q5T3P9

UniProt curated annotations — full annotation on UniProt →

Function. Beta-galactoside-binding lectin that acts as a sensor of membrane damage caused by infection and restricts the proliferation of infecting pathogens by targeting them for autophagy. Detects membrane rupture by binding beta-galactoside ligands located on the lumenal side of the endosome membrane; these ligands becoming exposed to the cytoplasm following rupture. Restricts infection by initiating autophagy via interaction with CALCOCO2/NDP52. Required to restrict infection of bacterial invasion such as S.typhimurium. Also required to restrict infection of Picornaviridae viruses. Has a marked preference for 3’-O-sialylated and 3’-O-sulfated glycans.

Subunit / interactions. Homodimer (PubMed:21288902, Ref.15). Interacts with CALCOCO2/NDP52. Interacts with PDPN; the interaction is glycosylation-dependent; may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix.

Subcellular location. Cytoplasmic vesicle. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitous. Selective expression by prostate carcinomas versus normal prostate and benign prostatic hypertrophy.

Domain organisation. Contains two homologous but distinct carbohydrate-binding domains.

Isoforms (2)

UniProt ID	Names	Canonical?
O00214-1	1, I	yes
O00214-2	2

RefSeq proteins (4): NP_006490, NP_963837, NP_963838, NP_963839 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001079	Galectin_CRD	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR044156	Galectin-like	Family

Pfam: PF00337

UniProt features (56 total): strand 26, sequence conflict 9, sequence variant 4, binding site 4, turn 3, helix 3, domain 2, mutagenesis site 2, chain 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5GZC	X-RAY DIFFRACTION	1.08
9FYJ	X-RAY DIFFRACTION	1.08
5GZD	X-RAY DIFFRACTION	1.19
9FXZ	X-RAY DIFFRACTION	1.3
5GZE	X-RAY DIFFRACTION	1.32
3AP9	X-RAY DIFFRACTION	1.33
6Z6Y	X-RAY DIFFRACTION	1.34
7ALS	X-RAY DIFFRACTION	1.35
4BMB	X-RAY DIFFRACTION	1.35
7P1M	X-RAY DIFFRACTION	1.52
3AP7	X-RAY DIFFRACTION	1.53
3AP6	X-RAY DIFFRACTION	1.58
5T7U	X-RAY DIFFRACTION	1.58
6W4Z	X-RAY DIFFRACTION	1.59
7AEN	X-RAY DIFFRACTION	1.6
8HL9	X-RAY DIFFRACTION	1.6
9KH4	X-RAY DIFFRACTION	1.75
5T7S	X-RAY DIFFRACTION	1.9
2YV8	X-RAY DIFFRACTION	1.92
3AP5	X-RAY DIFFRACTION	1.92
3APB	X-RAY DIFFRACTION	1.95
5T7T	X-RAY DIFFRACTION	1.96
3VKN	X-RAY DIFFRACTION	1.98
5GZG	X-RAY DIFFRACTION	2
4BME	X-RAY DIFFRACTION	2
5T7I	X-RAY DIFFRACTION	2
5GZF	X-RAY DIFFRACTION	2
4GXL	X-RAY DIFFRACTION	2.02
3VKO	X-RAY DIFFRACTION	2.08
5VWG	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00214-F1	91.14	0.82

Functional residue map

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

Catalytic / active sites (1): 59 (critical for binding to sialylated and sulfated oligosaccharides)

Ligand- & substrate-binding residues (4): 69; 79; 89; 249–255

Mutagenesis-validated functional residues (2):

Position	Phenotype
69	abolishes localization to cytoplasmic vesicles in case of infection by s.typhimurium.
190	does not affect localization to cytoplasmic vesicles in case of infection by s.typhimurium.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 272 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_B_CELL_ACTIVATION, GOZGIT_ESR1_TARGETS_DN, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_XENOPHAGY, GOBP_MACROAUTOPHAGY, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELL_CELL_ADHESION

GO Biological Process (6): plasma cell differentiation (GO:0002317), T cell costimulation (GO:0031295), cellular response to virus (GO:0098586), xenophagy (GO:0098792), lymphatic endothelial cell migration (GO:1904977), autophagy (GO:0006914)

GO Molecular Function (3): integrin binding (GO:0005178), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cytoplasm	2
mature B cell differentiation involved in immune response	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
response to virus	1
macroautophagy	1
defense response to other organism	1
lymph vessel morphogenesis	1
endothelial cell migration	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LGALS8	CALCOCO2	Q13137	996
LGALS8	ALCAM	Q13740	956
LGALS8	TRIM16	O95361	803
LGALS8	PDPN	Q86YL7	765
LGALS8	LGALS3	P17931	751
LGALS8	ITGAM	P11215	716
LGALS8	LRSAM1	Q6UWE0	644
LGALS8	TAX1BP1	Q86VP1	640
LGALS8	ITGA3	P26006	635
LGALS8	OPTN	Q96CV9	571
LGALS8	ITGB1	P05556	510
LGALS8	MTOR	P42345	509
LGALS8	GCSAM	Q8N6F7	491
LGALS8	MAP1LC3C	Q9BXW4	479
LGALS8	SQSTM1	Q13501	476

IntAct

87 interactions, top by confidence:

A	B	Type	Score
LGALS8	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.890
CALCOCO2	LGALS8	psi-mi:“MI:0915”(physical association)	0.890
TAX1BP1	LGALS8	psi-mi:“MI:0915”(physical association)	0.740
LGALS8	TAX1BP1	psi-mi:“MI:0915”(physical association)	0.740
APEH	LGALS8	psi-mi:“MI:0915”(physical association)	0.670
LGALS8	TRIM23	psi-mi:“MI:0915”(physical association)	0.670
TRIM23	LGALS8	psi-mi:“MI:0915”(physical association)	0.670
LGALS8	APEH	psi-mi:“MI:0915”(physical association)	0.670
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
TGIF1	LGALS8	psi-mi:“MI:0915”(physical association)	0.600
LGALS8	TGIF1	psi-mi:“MI:0915”(physical association)	0.600
TGIF1	LGALS8	psi-mi:“MI:0403”(colocalization)	0.600
LGALS8	TGIF1	psi-mi:“MI:0403”(colocalization)	0.600

BioGRID (419): LGALS8 (Two-hybrid), LGALS8 (Two-hybrid), TAX1BP1 (Two-hybrid), CALCOCO2 (Two-hybrid), MID2 (Two-hybrid), COLEC12 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), RNF13 (Affinity Capture-MS), SV2A (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), KIAA0319L (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), PTPRA (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q1N1R0, A4D1Z8, A8MUM7, D3ZGS3, O00214, O08573, O14727, O23547, O44126, O54891, O88644, O88879, P07583, P08520, P11762, P23668, P26788, P36573, P38552, P47967, P56180, P56217, P56470, P79238, P97400, P97840, Q01968, Q05315, Q09581, Q09605, Q29058, Q3MHZ8, Q62665, Q6DGJ1, Q6NVF0, Q801X7, Q8C726, Q8K419, Q8LEV3, Q8TCE9

Diamond homologs: A4D1Z8, C0HJQ1, C0HJR3, O00214, O44126, O54974, P05162, P07583, P08520, P08699, P09382, P11116, P11762, P16045, P16110, P23668, P26788, P38486, P47845, P47929, P47953, P48538, P56217, P81184, P82447, P97590, Q09581, Q29373, Q3MHZ8, Q49I35, Q5R7M1, Q62665, Q801X7, Q9CQW5, Q9Z144, O54891, A8MUM7, O00182, O08573, O88644

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	34
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625534	GRCh37/hg19 1q42.2-43(chr1:234546246-238716872)	Likely pathogenic

SpliceAI

2043 predictions. Top by Δscore:

Variant	Effect	Δscore
1:236538874:TATAG:T	acceptor_gain	1.0000
1:236538875:ATAGA:A	acceptor_gain	1.0000
1:236538876:T:G	acceptor_gain	1.0000
1:236538876:TAG:T	acceptor_loss	1.0000
1:236538876:TAGA:T	acceptor_gain	1.0000
1:236538877:A:AG	acceptor_gain	1.0000
1:236538878:G:GG	acceptor_gain	1.0000
1:236538878:G:GT	acceptor_loss	1.0000
1:236538878:GATTC:G	acceptor_gain	1.0000
1:236539090:GTAG:G	donor_loss	1.0000
1:236539091:T:A	donor_loss	1.0000
1:236540679:GCTCG:G	donor_gain	1.0000
1:236541693:GAGA:G	donor_gain	1.0000
1:236541696:A:AG	donor_gain	1.0000
1:236542788:G:GG	donor_gain	1.0000
1:236543649:GT:G	donor_loss	1.0000
1:236543650:T:A	donor_loss	1.0000
1:236544745:A:AG	acceptor_gain	1.0000
1:236548143:GGAA:G	donor_gain	1.0000
1:236548144:G:GT	donor_gain	1.0000
1:236548147:G:GG	donor_gain	1.0000
1:236550986:TTCAT:T	acceptor_gain	1.0000
1:236550988:CAT:C	acceptor_gain	1.0000
1:236550991:C:CC	acceptor_gain	1.0000
1:236551994:ATTAC:A	donor_loss	1.0000
1:236551995:TTA:T	donor_loss	1.0000
1:236551996:TACC:T	donor_loss	1.0000
1:236551997:A:AT	donor_loss	1.0000
1:236552001:T:A	donor_gain	1.0000
1:236552103:CGAAC:C	acceptor_gain	1.0000

AlphaMissense

2117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:236539000:T:A	W86R	0.999
1:236539000:T:C	W86R	0.999
1:236539002:G:C	W86C	0.999
1:236539002:G:T	W86C	0.999
1:236538881:T:C	F46S	0.997
1:236538937:C:G	H65D	0.997
1:236544838:T:C	S243P	0.997
1:236538880:T:C	F46L	0.996
1:236538882:C:A	F46L	0.996
1:236538882:C:G	F46L	0.996
1:236538893:T:C	L50P	0.996
1:236544794:T:C	L228P	0.996
1:236548048:G:C	A281P	0.996
1:236537561:G:A	G37E	0.995
1:236539001:G:C	W86S	0.995
1:236539085:T:C	F114S	0.995
1:236540567:G:C	A117P	0.995
1:236544758:T:A	V216D	0.995
1:236544764:T:C	L218P	0.995
1:236544791:C:A	A227D	0.995
1:236548046:T:A	V280D	0.995
1:236537560:G:T	G37W	0.994
1:236538935:T:C	F64S	0.994
1:236543612:T:A	V201D	0.994
1:236543618:T:A	V203D	0.994
1:236544809:G:C	R233P	0.994
1:236544856:T:A	W249R	0.994
1:236544856:T:C	W249R	0.994
1:236544893:T:C	F261S	0.994
1:236548040:T:C	F278S	0.994

dbSNP variants (sampled 300 via entrez): RS1000078302 (1:236543004 T>C), RS1000104764 (1:236516431 T>A,G), RS1000134814 (1:236528707 T>C), RS1000278248 (1:236528046 T>A,C), RS1000292001 (1:236534938 G>A), RS1000383743 (1:236544837 T>G), RS1000391681 (1:236527804 C>T), RS1000579019 (1:236522362 G>A), RS1000734036 (1:236545064 T>A), RS1000803050 (1:236545166 A>G), RS1000823086 (1:236534041 T>C,G), RS1000831805 (1:236549098 C>T), RS1000949475 (1:236517644 A>C), RS1000964296 (1:236518128 A>G), RS1001133948 (1:236543737 A>G)

Disease associations

OMIM: gene MIM:606099 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90002400_546	Plateletcrit	2.000000e-14
GCST90002401_407	Platelet distribution width	2.000000e-16
GCST90002402_267	Platelet count	6.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5475 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 579 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL5314358	LACTOSE, ANHYDROUS	3
CHEMBL4297442	OLITIGALTIN	2	559
CHEMBL5182222	SELVIGALTIN	2	20

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

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-4-[(butylcarbamothioyl)amino]-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	23000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-{[(3-hydroxypropyl)carbamothioyl]amino}oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	23000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(prop-2-en-1-ylcarbamothioyl)amino]oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	34000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-4-[(cyclohexylcarbamothioyl)amino]-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	40000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-4-(carbamothioylamino)-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	43000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(phenylcarbamothioyl)amino]oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	45000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-4-[(diethylcarbamothioyl)amino]-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	46000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(methylcarbamothioyl)amino]oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	49000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-3,5-dihydroxy-4-{[(2-hydroxyethyl)carbamothioyl]amino}-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	49000 nM
N-[(2R,3R,4R,5S,6R)-5-{[(2S,3R,4S,5R,6R)-4-({[(2S,3R,4S,5R,6R)-2-{[(2R,3S,4R,5R,6R)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-3-yl]oxy}-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]carbamothioyl}amino)-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-hydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]acetamide	KD	58000 nM
N-[(2R,3R,4R,5S,6R)-4-hydroxy-6-(hydroxymethyl)-2-methoxy-5-{[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}oxan-3-yl]acetamide	KD	70000 nM

ChEMBL bioactivities

31 potent at pChembl≥5 of 110 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.64	Kd	0.23	nM	CHEMBL1669631
9.63	Kd	0.233	nM	CHEMBL1669631
8.81	Kd	1.55	nM	CHEMBL1669628
8.80	Kd	1.6	nM	CHEMBL1669628
7.61	Kd	24.6	nM	CHEMBL1669628
7.60	Kd	25	nM	CHEMBL1669628
7.51	Kd	31	nM	CHEMBL1669630
7.50	Kd	31.3	nM	CHEMBL1669630
7.43	Kd	37	nM	CHEMBL1669630
7.43	Kd	36.9	nM	CHEMBL1669630
7.31	Kd	49	nM	CHEMBL1669631
6.31	Kd	490	nM	CHEMBL1669631
5.82	Kd	1500	nM	CHEMBL4854378
5.75	Kd	1800	nM	CHEMBL4858277
5.70	Kd	2010	nM	CHEMBL5436399
5.69	Kd	2060	nM	CHEMBL5421354
5.64	Kd	2300	nM	CHEMBL3764379
5.55	Kd	2800	nM	CHEMBL4872829
5.25	Kd	5600	nM	CHEMBL5436190
5.24	Kd	5720	nM	CHEMBL4745577
5.22	Kd	6040	nM	CHEMBL5428395
5.14	Kd	7300	nM	CHEMBL5427260
5.10	Kd	8000	nM	CHEMBL5439240
5.09	Kd	8200	nM	CHEMBL5434120
5.08	Kd	8300	nM	CHEMBL5428395
5.05	Kd	8900	nM	SELVIGALTIN
5.04	Kd	9170	nM	CHEMBL4749475
5.03	Kd	9400	nM	CHEMBL5436075
5.03	Kd	9400	nM	CHEMBL5421500
5.02	Kd	9470	nM	CHEMBL4749028
5.02	Kd	9600	nM	CHEMBL5441028

PubChem BioAssay actives

31 with measured affinity, of 389 total; 21 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(2S,3R,4R,5S,6R)-4-hydroxy-6-(hydroxymethyl)-2-(12-sulfanyldodecoxy)-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-3-yl]acetamide	567915: Binding affinity to human galectin-8 component 1 by surface plasmon resonance method	kd	0.0002	uM
(3R,4S,5R,6R)-2-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-(12-sulfanyldodecoxy)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol	567915: Binding affinity to human galectin-8 component 1 by surface plasmon resonance method	kd	0.0015	uM
(2S,3R,4S,5R,6R)-2-[(2R,3S,4R,6S)-4-hydroxy-2-(hydroxymethyl)-6-(12-sulfanyldodecoxy)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol	567916: Binding affinity to human galectin-8 component 2 by surface plasmon resonance method	kd	0.0310	uM
2-[[(2R,3R,4S,5S,6R)-2-(3,4-dichlorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxymethyl]quinoline-7-carboxylic acid	1772870: Binding affinity to galectin-8 N-terminal domain (unknown origin)	kd	1.5000	uM
2-[[(2R,3R,4S,5S,6R)-2-(3,4-dichlorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxymethyl]-3-methylbenzimidazole-5-carboxylic acid	1772855: Binding affinity to human galactin-8 N terminal domain assessed as dissociation constant by competitive fluorescence polarization assay	kd	1.8000	uM
5-(3,4-dichlorophenoxy)-N-(2-oxochromen-6-yl)sulfonyl-1H-indole-2-carboxamide	2036516: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry analysis	kd	2.0100	uM
N-(3-benzylthiophen-2-yl)sulfonyl-5-(3,4-dichlorophenoxy)-1H-indole-2-carboxamide	2036516: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry analysis	kd	2.0600	uM
(2S,4S,5R,6R)-5-acetamido-2-[(2R,3S,4S,5R,6S)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3S,4R,5R,6R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid	1675450: Binding affinity to N-terminal domain of human galectin-8 (8-154 residues) by ITC assay	kd	2.3000	uM
2-[[(2R,3R,4S,5S,6R)-2-(3,4-dichlorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxymethyl]-3H-benzimidazole-5-carboxylic acid	1772855: Binding affinity to human galactin-8 N terminal domain assessed as dissociation constant by competitive fluorescence polarization assay	kd	2.8000	uM
N-(3-benzyl-5-chlorothiophen-2-yl)sulfonyl-5-(3,4-dichlorophenoxy)-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	5.6000	uM
1-O-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl] 3-O-(4-fluorophenyl) propanedioate	1675450: Binding affinity to N-terminal domain of human galectin-8 (8-154 residues) by ITC assay	kd	5.7200	uM
N-(1,3-benzothiazol-6-ylsulfonyl)-5-(3,4-dichlorophenoxy)-1H-indole-2-carboxamide	2036516: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry analysis	kd	6.0400	uM
5-(4-bromo-2-fluorophenoxy)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	7.3000	uM
5-(4-bromo-3-fluorophenoxy)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	8.0000	uM
N-(1-benzothiophen-3-ylsulfonyl)-5-(3,4-dichlorophenoxy)-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	8.2000	uM
(2R,3R,4S,5R,6R)-2-[(5-bromo-3-pyridinyl)sulfanyl]-6-(hydroxymethyl)-4-[4-(3,4,5-trifluorophenyl)triazol-1-yl]oxane-3,5-diol	1857060: Binding affinity to human C-terminal domain of Galectin-8 assessed as dissociation constant by fluorescence polarization	kd	8.9000	uM
1-O-benzyl 3-O-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl] propanedioate	1675450: Binding affinity to N-terminal domain of human galectin-8 (8-154 residues) by ITC assay	kd	9.1700	uM
5-(4-bromo-3-chlorophenoxy)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	9.4000	uM
5-(3,4-dichlorophenoxy)-N-(2,4-dichlorophenyl)sulfonyl-1H-indole-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	9.4000	uM
1-O-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl] 3-O-(4-methoxyphenyl) propanedioate	1675450: Binding affinity to N-terminal domain of human galectin-8 (8-154 residues) by ITC assay	kd	9.4700	uM
5-(3,4-dichlorophenoxy)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-1-benzofuran-2-carboxamide	2036510: Binding affinity to C-terminal domain human Gal-8 expressed in Escherichia coli BL21 (DE3) cells by competitive fluorescence polarization assay	kd	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects cotreatment, affects expression, increases expression	5
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	3
Tretinoin	affects cotreatment, increases expression	3
cobaltous chloride	increases expression	2
mercuric bromide	affects cotreatment, increases expression	2
Arsenic Trioxide	affects expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Benzene	increases expression	2
Ozone	decreases expression, increases abundance, affects expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
monomethylarsonic acid	affects cotreatment, affects expression	1
perfluorooctanoic acid	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
dimethylarsine	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1

ChEMBL screening assays

63 unique, capped per target: 63 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013542	Binding	Binding affinity to galectin 8N terminal domain at 20 degC by fluorescence polarization assay	Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NJ	Abcam K-562 LGALS8 KO	Cancer cell line	Female
CVCL_D2K4	Abcam Raji LGALS8 KO	Cancer cell line	Male
CVCL_UQ85	Abcam Jurkat LGALS8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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