SELL

Summary

SELL (selectin L, HGNC:10720) is a protein-coding gene on chromosome 1q24.2, encoding L-selectin (P14151). Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells.

This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6402 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 61 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10720
Approved symbol	SELL
Name	selectin L
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	LSEL, LAM1, LAM-1, hLHRc, Leu-8, Lyam-1, PLNHR, CD62L
Ensembl gene	ENSG00000188404
Ensembl biotype	protein_coding
OMIM	153240
Entrez	6402

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000236147, ENST00000460650, ENST00000463108, ENST00000466340, ENST00000479657, ENST00000497295, ENST00000650983, ENST00000878074, ENST00000878075

RefSeq mRNA: 1 — MANE Select: NM_000655 NM_000655

CCDS: CCDS53427

Canonical transcript exons

ENST00000236147 — 9 exons

Exon	Start	End
ENSE00000789630	169701560	169701688
ENSE00001131673	169690667	169691802
ENSE00003486796	169710436	169710517
ENSE00003523497	169707342	169707449
ENSE00003525031	169711496	169711620
ENSE00003554358	169696535	169696553
ENSE00003617246	169704568	169704753
ENSE00003661854	169703255	169703440
ENSE00003672522	169708417	169708803

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 99.63.

FANTOM5 (CAGE): breadth broad, TPM avg 67.1180 / max 7235.4291, expressed in 451 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15860	63.2334	444
15859	2.3393	173
15858	1.4166	147
15856	0.0900	12
15857	0.0386	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.63	gold quality
monocyte	CL:0000576	99.50	gold quality
leukocyte	CL:0000738	99.49	gold quality
mononuclear cell	CL:0000842	99.49	gold quality
granulocyte	CL:0000094	99.19	gold quality
bone marrow	UBERON:0002371	98.36	gold quality
vermiform appendix	UBERON:0001154	98.09	gold quality
bone marrow cell	CL:0002092	97.72	gold quality
spleen	UBERON:0002106	97.40	gold quality
trabecular bone tissue	UBERON:0002483	97.24	gold quality
lymph node	UBERON:0000029	96.70	gold quality
periodontal ligament	UBERON:0008266	96.13	gold quality
caecum	UBERON:0001153	91.15	gold quality
nasopharynx	UBERON:0001728	90.10	gold quality
epithelium of nasopharynx	UBERON:0001951	90.10	gold quality
gall bladder	UBERON:0002110	89.23	gold quality
thymus	UBERON:0002370	88.30	gold quality
right lung	UBERON:0002167	87.71	gold quality
superficial temporal artery	UBERON:0001614	85.80	gold quality
upper lobe of left lung	UBERON:0008952	85.32	gold quality
tonsil	UBERON:0002372	84.34	gold quality
upper lobe of lung	UBERON:0008948	83.78	gold quality
colonic epithelium	UBERON:0000397	82.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.64	gold quality
pituitary gland	UBERON:0000007	81.07	gold quality
adenohypophysis	UBERON:0002196	79.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.20	gold quality
rectum	UBERON:0001052	79.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.66	gold quality
spinal cord	UBERON:0002240	78.26	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	1702.82
E-CURD-6	yes	1171.64
E-GEOD-110499	yes	1141.06
E-MTAB-9067	yes	1066.31
E-MTAB-6701	yes	812.67
E-CURD-79	yes	678.86
E-CURD-95	yes	673.27
E-MTAB-8911	yes	526.97
E-CURD-88	yes	518.68
E-HCAD-1	yes	98.33
E-CURD-122	yes	88.75
E-HCAD-8	yes	55.66
E-CURD-120	yes	52.45
E-HCAD-6	yes	44.43
E-HCAD-10	yes	30.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, FOXO1, IKZF1, IRF1, KLF2, MZF1, SP1

miRNA regulators (miRDB)

65 targeting SELL, 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-4533	100.00	69.48	2758
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055

Literature-anchored findings (GeneRIF, showing 40)

• The cytoplasmic domain of L-selectin regulates shedding by a mechanism in which bound calmodulin may operate as a negative effector. (PMID:11466384)
• interacts with oversulfated chondroitin/dermatan sulfates containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) (PMID:11821431)
• two SNPs in the E-selectin gene and six SNPs in the L-selectin gene were significantly associated with IgAN in Japanese patients (PMID:11828340)
• L-selectin dimerization enhances tether formation to properly spaced ligand. (PMID:11907045)
• destabilization of L-selectin-mediated lymphocyte rolling by endothelial chemokines (PMID:12042326)
• does not play a role in homing and clonogenic outgrowth of CD34(+) peripheral blood stem cells (PMID:12063026)
• review of structure, function, cell and tissue distribution (PMID:12144128)
• Data show that tumor necrosis factor-alpha-converting enzyme (TACE)is involved in the shedding of L-selectin by NSAIDS in human neutrophils. (PMID:12147693)
• CD62L on human cultured T lymphoblasts is one of several glycoproteins that interacts directly with E-selectin and contributes to rolling under flow. (PMID:12165498)
• circulating soluble selectitn L in acute myeloid leukemia is correlaed with peripheral blast cell counts, extramedullaary infiltration, relapse and mortality (PMID:12186696)
• Protein polymorphism is associated with diabetic nephropathy in type 2 diabetes mellitus (PMID:12200076)
• Conjunctival biopsies excised from patients following cataract surgery provided circumstantial evidence that endothelial L-selectin might play a role in the surgery-induced up-regulation of leukocyte rolling. (PMID:12200386)
• data provide a comprehensive comparison of the L-selectin/cytoskeletal interaction with other functionally important surface antigens (PMID:12202158)
• L-selectin initiates leukocyte/endothelial cell interactions leading to leukocyte rolling and migration which are then optimized by CD18 integrin/ICAM-1 cooperative interactions. (PMID:12370391)
• that L-selectin was colocalized with high-affinity CD18.Adhesion signaled via L-selectin coincided with the kinetics of MAPK phosphorylation and was inhibited by blocking p38 or p42/44 activity. (PMID:12431911)
• L-selectin is expressed in memory CD4+ T cells that are smaller, proliferate well in response to tetanus toxoid, have longer telomeres, and express genes and proteins consistent with immune surveillance function. (PMID:12496379)
• results suggest that trophoblast L-selectin mediates interactions with the uterus and that this adhesion mechanism may be critical to establishing human pregnancy (PMID:12532021)
• L-selectin mobilized intracellular CXCR4 to significantly increase surface CXCR4 stimulation and inhibited SDF-1 induced CXCR4 internalization. (PMID:12609846)
• L-selectin binds with high affinity to the N-terminal region of PSGL-1 through cooperative interactions with three sulfated tyrosine residues and an appropriately positioned C2-O-sLex O-glycan. (PMID:12736247)
• interacts with Helicobacter pylori isolates from patients with chronic gastritis, duodenal ulcer and gastric cancer (PMID:12738381)
• Monitoring of the plasma level of sL-selectin is possibly useful for early diagnosis of relapse and extramedullary infiltration in acute leukemia. (PMID:12844406)
• Anaplasma phagocytophilum infected neutrophils showed reduced expression of P-selectin glycoprotein ligand 1 (PSGL-1, CD162) and L-selectin (CD62L) (PMID:12874338)
• expression on leukocytes in Behcet’s disease. (PMID:12918706)
• Strong relationship between soluble L-selectin and diabetic retinopathy. strong correlation between sL-selectin and HbA1c. Soluble L-selectin is increased with poor glycemic control. (PMID:14533031)
• engagement of both CD4 and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting CD4(+) T cells. (PMID:14576059)
• Importance of CD62L expression on lymphocytes for recurrent miscarriage and the relevance of the maternal response to microbial antigens during pregnancy should be further explored. (PMID:14585903)
• L-selectin tethers appear adapted to undergo rapid avidity enhancement by cellular transport, a specialized mechanism not used by any other known adhesion receptor. (PMID:14597772)
• L-selectin mediates adhesion at all shear rates. Mocyte-expressed L-selectin functionally mediates primary tethering of monocytes to endothelial-cell ccarbohydrate ligands. L-selectin blockade without PMCs had an inhibitory effect on monocyte adhesion. (PMID:14615387)
• positive marker for precinical type 1 diabetes in children (PMID:14737745)
• LSEL expression is increased by biochemical engineering of sialic acids. (PMID:15093751)
• results suggest that ezrin-radixin-moesin proteins are required for microvillar positioning of L-selectin and that this is important both for leukocyte tethering and L-selectin shedding (PMID:15178693)
• L-selectin signal transduction requires protein kinase C alpha, iota, and theta binding (PMID:15192100)
• L-selectin plays a role in the vascular homing of peripheral blood-derived endothelial progenitor cells. (PMID:15470072)
• describes currently known binding partners of the L-selectin tail and how their associations affect L-selectin function. (review) (PMID:15506984)
• There was significantly more soluble L-selectin in serum samples from subjects with cryptococcosis than in those from uninfected subjects (PMID:15776384)
• Increased expression of L-selectin ligand in the human endometrium during the early and midsecretory phases of the menstrual cycle may be related to the process of implantation. (PMID:15831305)
• Serum levels were measured with enzyme-linked immunosorbent assays over the first 2 years of life in 65 children seroconverting to positivity for autoantibodies and 65 control children, all with susceptibility to type 1 diabetes. (PMID:16270299)
• variant isoforms of CD44 on LS174T colon carcinoma cells possess selectin binding activity, in contrast to the standard isoform of CD44 on hematopoietic-progenitor cells. (PMID:16352650)
• The 206Leu allele frequency occurred in 42% of the patients with coronary artery disease compared to 30% of the controls (p<0.009). (PMID:16357481)
• expression of HCELL confers robust and predominant tumor cell binding to E- and L-selectin (PMID:16565092)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sell	ENSMUSG00000026581
rattus_norvegicus	Sell	ENSRNOG00000002776

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

L-selectin — P14151 (reviewed: P14151)

Alternative names: CD62 antigen-like family member L, Leukocyte adhesion molecule 1, Leukocyte surface antigen Leu-8, Leukocyte-endothelial cell adhesion molecule 1, Lymph node homing receptor, TQ1, gp90-MEL

All UniProt accessions (2): A0A494C0S7, P14151

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia.

Subunit / interactions. Interaction with SELPLG/PSGL1 and PODXL2 is required for promoting recruitment and rolling of leukocytes. This interaction is dependent on the sialyl Lewis X glycan modification of SELPLG and PODXL2, and tyrosine sulfation modifications of SELPLG. Sulfation on ‘Tyr-51’ of SELPLG is important for L-selectin binding.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in B-cell lines and T-lymphocytes.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the selectin/LECAM family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14151-1	1	yes
P14151-2	2

RefSeq proteins (1): NP_000646* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000742	EGF	Domain
IPR001304	C-type_lectin-like	Domain
IPR002396	Selectin_superfamily	Family
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR016348	L-selectin	Family
IPR018378	C-type_lectin_CS	Conserved_site
IPR033991	Selectin_CTLD	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR050350	Compl-Cell_Adhes-Reg	Family

Pfam: PF00008, PF00059, PF00084

UniProt features (61 total): strand 11, disulfide bond 9, glycosylation site 6, binding site 5, sequence conflict 5, sequence variant 4, mutagenesis site 4, helix 4, domain 4, topological domain 2, turn 2, signal peptide 1, propeptide 1, chain 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5VC1	X-RAY DIFFRACTION	1.94
3CFW	X-RAY DIFFRACTION	2.2
2LGF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14151-F1	84.76	0.69

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 (5): 118; 120; 126; 143; 144

Disulfide bonds (9): 57–155, 128–147, 160–171, 165–180, 182–191, 197–241, 227–254, 259–303, 289–316

Glycosylation sites (6): 60, 104, 177, 232, 246, 271

Mutagenesis-validated functional residues (4):

Position	Phenotype
60	loss of one glycosylation site.
104	loss of one glycosylation site.
126	impairs interaction with cognate oligosaccharide. abolishes cell rolling on glycan ligands.
177	loss of one glycosylation site.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 398 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, CHUNG_BLISTER_CYTOTOXICITY_DN, MODULE_45, MODULE_64, GOZGIT_ESR1_TARGETS_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GNF2_LYN

GO Biological Process (8): cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), leukocyte cell-cell adhesion (GO:0007159), calcium-dependent cell-cell adhesion (GO:0016339), response to cytokine (GO:0034097), leukocyte tethering or rolling (GO:0050901), leukocyte migration (GO:0050900), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742)

GO Molecular Function (9): protease binding (GO:0002020), calcium ion binding (GO:0005509), heparin binding (GO:0008201), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), glycosphingolipid binding (GO:0043208), oligosaccharide binding (GO:0070492), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	1
Hemostasis	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
binding	2
cellular process	1
response to peptide	1
cellular extravasation	1
leukocyte adhesion to vascular endothelial cell	1
immune system process	1
cell migration	1
enzyme binding	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
sphingolipid binding	1
glycolipid binding	1
carbohydrate binding	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELL	CD44	P16070	998
SELL	SELPLG	Q14242	997
SELL	NTAN1	Q96AB6	995
SELL	MADCAM1	Q13477	993
SELL	CD34	P28906	992
SELL	SELE	P16111	984
SELL	SELP	P16109	983
SELL	VCAM1	P19320	969
SELL	ITGB2	P05107	965
SELL	CCL19	Q99731	932
SELL	CCL21	O00585	924
SELL	CD4	P01730	921
SELL	ICAM1	P05362	921
SELL	CD8A	P01732	920
SELL	CCR7	P32248	913

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SELL	SELPLG	psi-mi:“MI:0407”(direct interaction)	0.440
SELL	PODXL	psi-mi:“MI:0407”(direct interaction)	0.440
CD34	SELL	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (18): EMCN (Affinity Capture-Western), SELL (Reconstituted Complex), SELL (Two-hybrid), PODXL (Affinity Capture-Western), CFH (Reconstituted Complex), GRB2 (Affinity Capture-Western), MUC7 (Reconstituted Complex), SELL (Affinity Capture-RNA), VCAN (Reconstituted Complex), MSN (Reconstituted Complex), EZR (Reconstituted Complex), SELE (Affinity Capture-Luminescence), SELL (Affinity Capture-MS), SELL (Biochemical Activity), SELL (Biochemical Activity)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P08607, P14151, P15529, P16109, P17690, P19070, P20023, P26644, P27113, P30836, P42201, P49457, P70105, P79138, P98107, P98109, P98131, Q01102, Q03472, Q07968, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
C5AR2	“down-regulates quantity by repression”	SELL
C5AR1	“down-regulates quantity by repression”	SELL

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1457087	NC_000001.10:g.(?169660781)(170521603_?)del	Pathogenic

SpliceAI

1359 predictions. Top by Δscore:

Variant	Effect	Δscore
1:169692934:ATGC:A	donor_gain	1.0000
1:169703444:CAA:C	acceptor_gain	1.0000
1:169704564:TCA:T	donor_loss	1.0000
1:169704565:CA:C	donor_loss	1.0000
1:169704566:A:AT	donor_loss	1.0000
1:169704754:C:CC	acceptor_gain	1.0000
1:169704757:CAA:C	acceptor_gain	1.0000
1:169704758:A:T	acceptor_gain	1.0000
1:169704759:A:AC	acceptor_gain	1.0000
1:169704759:A:C	acceptor_gain	1.0000
1:169707462:C:CT	acceptor_gain	1.0000
1:169707463:A:T	acceptor_gain	1.0000
1:169710433:TA:T	donor_loss	1.0000
1:169710434:A:AC	donor_gain	1.0000
1:169710434:ACC:A	donor_loss	1.0000
1:169710435:C:CC	donor_gain	1.0000
1:169710435:CCA:C	donor_gain	1.0000
1:169710435:CCAC:C	donor_loss	1.0000
1:169710513:AATAT:A	acceptor_gain	1.0000
1:169710514:ATAT:A	acceptor_gain	1.0000
1:169710515:TAT:T	acceptor_gain	1.0000
1:169710516:AT:A	acceptor_gain	1.0000
1:169710516:ATCT:A	acceptor_loss	1.0000
1:169710517:TC:T	acceptor_loss	1.0000
1:169710518:C:CC	acceptor_gain	1.0000
1:169710518:CTGCA:C	acceptor_loss	1.0000
1:169710519:T:A	acceptor_loss	1.0000
1:169710524:A:AC	acceptor_gain	1.0000
1:169691803:C:CC	acceptor_gain	0.9900
1:169703249:A:AC	donor_gain	0.9900

AlphaMissense

2479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:169708463:C:A	W142C	0.999
1:169708463:C:G	W142C	0.999
1:169708547:C:A	W114C	0.999
1:169708547:C:G	W114C	0.999
1:169708465:A:G	W142R	0.998
1:169708465:A:T	W142R	0.998
1:169708595:C:A	W98C	0.996
1:169708595:C:G	W98C	0.996
1:169708614:C:G	R92P	0.995
1:169708625:C:A	W88C	0.995
1:169708625:C:G	W88C	0.995
1:169708425:C:G	C155S	0.994
1:169708426:A:T	C155S	0.994
1:169708506:C:G	C128S	0.994
1:169708507:A:T	C128S	0.994
1:169708549:A:G	W114R	0.994
1:169708549:A:T	W114R	0.994
1:169708589:C:A	W100C	0.994
1:169708589:C:G	W100C	0.994
1:169708718:G:C	C57W	0.994
1:169708739:C:A	W50C	0.994
1:169708739:C:G	W50C	0.994
1:169708424:A:C	C155W	0.993
1:169708436:C:A	K151N	0.993
1:169708436:C:G	K151N	0.993
1:169708597:A:G	W98R	0.993
1:169708597:A:T	W98R	0.993
1:169708627:A:G	W88R	0.992
1:169708627:A:T	W88R	0.992
1:169708719:C:G	C57S	0.992

dbSNP variants (sampled 300 via entrez): RS1000152051 (1:169692717 A>G), RS1000309026 (1:169708874 A>C), RS1000319323 (1:169692285 G>C,T), RS1000394800 (1:169702228 G>A), RS1000435304 (1:169692002 T>C), RS1000664874 (1:169704345 C>T), RS1000718175 (1:169704725 TG>T), RS1000920143 (1:169700468 T>C), RS1001061058 (1:169698396 C>T), RS1001086853 (1:169713449 C>T), RS1001172049 (1:169703544 T>C), RS1001505801 (1:169706841 C>T), RS1001986202 (1:169697332 C>G), RS1002001265 (1:169703377 G>A,T), RS1002038518 (1:169697646 C>A)

Disease associations

OMIM: gene MIM:153240 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000406_8	Amyotrophic lateral sclerosis	4.000000e-06
GCST002329_1	Acne (severe)	1.000000e-08
GCST003043_84	Inflammatory bowel disease	3.000000e-08
GCST006585_2183	Blood protein levels	6.000000e-48
GCST010107_10	L-selectin levels	1.000000e-07
GCST010107_13	L-selectin levels	7.000000e-20
GCST010107_18	L-selectin levels	1.000000e-08
GCST010107_3	L-selectin levels	2.000000e-06
GCST90002380_116	Basophil percentage of white cells	7.000000e-10
GCST90002382_16	Eosinophil percentage of white cells	6.000000e-11
GCST90002393_164	Monocyte count	4.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008202	L-Selectin measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0007991	eosinophil percentage of leukocytes
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3161 (SINGLE PROTEIN), CHEMBL3831288 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 103,233 (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
CHEMBL288114	GALLIC ACID	2	103,233

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

ChEMBL bioactivities

29 potent at pChembl≥5 of 51 total, top 29 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.16	IC50	700	nM	CHEMBL3351094
6.10	IC50	800	nM	CHEMBL3351095
6.10	IC50	790	nM	CHEMBL375763
6.00	IC50	1000	nM	CHEMBL112796
5.96	IC50	1100	nM	CHEMBL220720
5.85	IC50	1400	nM	CHEMBL221163
5.82	IC50	1500	nM	CHEMBL220254
5.80	IC50	1600	nM	CHEMBL3351093
5.80	IC50	1600	nM	CHEMBL223010
5.80	IC50	1600	nM	CHEMBL373592
5.75	IC50	1800	nM	CHEMBL3351089
5.64	IC50	2300	nM	CHEMBL220419
5.63	IC50	2340	nM	CHEMBL3215517
5.62	IC50	2400	nM	CHEMBL450011
5.52	IC50	3000	nM	CHEMBL112485
5.51	IC50	3100	nM	CHEMBL2303665
5.51	IC50	3100	nM	CHEMBL386951
5.48	IC50	3300	nM	CHEMBL220997
5.42	IC50	3800	nM	CHEMBL133134
5.40	IC50	4000	nM	CHEMBL2303755
5.40	IC50	4000	nM	CHEMBL3215516
5.38	IC50	4200	nM	CHEMBL2303665
5.38	IC50	4200	nM	CHEMBL220560
5.37	IC50	4300	nM	CHEMBL220340
5.36	IC50	4400	nM	CHEMBL2303665
5.24	IC50	5700	nM	CHEMBL376200
5.06	IC50	8700	nM	CHEMBL220828
5.01	IC50	9700	nM	CHEMBL426376
5.01	IC50	9800	nM	CHEMBL386952

PubChem BioAssay actives

29 with measured affinity, of 143 total; 27 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
(4R)-5-(methylamino)-5-oxo-4-[[(2R)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	0.7000	uM
2-[5-[4-[[3-(2,3,4-trihydroxyphenyl)benzoyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	0.7900	uM
(4R)-5-(methylamino)-5-oxo-4-[[(2S)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	0.8000	uM
1-[4-methoxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]phenyl]cyclohexane-1-carboxylic acid	95568: Inhibitory activity against L-selectin IgG chimeras binding to sLex coating 96 wells using competitive cell-free ELISA assay was determined.	ic50	1.0000	uM
2-[5-[3-[[3-(2,3,4-trihydroxyphenyl)benzoyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	1.1000	uM
3-[[2-(3,4,5-trihydroxyphenyl)acetyl]amino]benzoic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	1.4000	uM
2-[3-[2-(3,4,5-trihydroxybenzoyl)oxyphenyl]phenyl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	1.5000	uM
(4S)-5-(methylamino)-5-oxo-4-[[(2R)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	1.6000	uM
5-[2-[[3-(2,3,4-trihydroxyphenyl)benzoyl]amino]phenyl]thiophene-2-carboxylic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	1.6000	uM
2-[5-[2-[[4-(2,3,4-trihydroxyphenyl)benzoyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	1.6000	uM
(4S)-5-(methylamino)-5-oxo-4-[[(2S)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	1.8000	uM
2-[3-[3-(3,4,5-trihydroxyphenyl)propanoylamino]phenyl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	2.3000	uM
3-[(2S,5R)-3,6-dioxo-7-(2-tetradecylhexadecyl)-5-[[(2S,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-1,4,7-thiadiazecan-2-yl]propanoic acid	202718: In vitro inhibitory activity of compound was determined against Selectin L binding by ELISA assay	ic50	2.3400	uM
5-methoxy-5-oxo-4-[[(2R)-2-(2-tetradecylhexadecanoylamino)-3-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	2.4000	uM
2-[4-methoxy-3-(3,4,5-trihydroxy-6-methyloxan-2-yl)phenyl]acetic acid	95568: Inhibitory activity against L-selectin IgG chimeras binding to sLex coating 96 wells using competitive cell-free ELISA assay was determined.	ic50	3.0000	uM
2-[5-[2-[[2-(3,4,5-trihydroxyphenyl)acetyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	3.1000	uM
(4R)-5-(methylamino)-5-oxo-4-[[(2S)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	3.1000	uM
4-[[2-(3,4,5-trihydroxyphenyl)acetyl]amino]cyclohexane-1-carboxylic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	3.3000	uM
4-(methylamino)-4-oxo-3-[[(2R)-2-(2-tetradecylhexadecanoylamino)-3-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxypropanoyl]amino]butanoic acid	202721: Inhibition of Selectin L binding	ic50	3.8000	uM
(4S)-5-(methylamino)-5-oxo-4-[[(2R)-2-(2-tetradecylhexadecanoylamino)-3-[(2S,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropanoyl]amino]pentanoic acid	202721: Inhibition of Selectin L binding	ic50	4.0000	uM
(4R)-5-(methylamino)-5-oxo-4-[[(2S)-2-(2-tetradecylhexadecanoylamino)-3-[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropanoyl]amino]pentanoic acid	202718: In vitro inhibitory activity of compound was determined against Selectin L binding by ELISA assay	ic50	4.0000	uM
4-methyl-3-[3-(3,4,5-trihydroxyphenyl)propanoylamino]benzoic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	4.2000	uM
2-[5-[2-[[(E)-3-(2,3,4-trihydroxyphenyl)prop-2-enoyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	4.3000	uM
4-[3-(3,4,5-trihydroxyphenyl)propanoylamino]cyclohexane-1-carboxylic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	5.7000	uM
2-[3-[2-[[2-(3,4,5-trihydroxyphenyl)acetyl]amino]phenyl]phenyl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	8.7000	uM
2-[5-[2-[[2-[3-(2,3,4-trihydroxyphenyl)phenyl]acetyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	9.7000	uM
2-[5-[2-[[3-(2,3,4-trihydroxyphenyl)benzoyl]amino]phenyl]thiophen-2-yl]acetic acid	280293: Inhibition of human L-selectin after 2 hrs	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Calcimycin	affects cotreatment, decreases reaction, increases expression, decreases expression	2
Resveratrol	decreases expression, decreases reaction, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Heparin	decreases expression, increases expression	2
Indomethacin	decreases expression	2
Lipopolysaccharides	decreases expression	2
Methotrexate	decreases expression	2
Plant Extracts	decreases reaction, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
GSK-J4	decreases expression	1
fulvic acid	affects cotreatment, decreases reaction, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression, decreases reaction	1
Lipofundin	decreases expression	1
nimesulide	decreases expression	1
afimoxifene	increases expression	1
sodium arsenite	increases expression	1
endotoxin, Escherichia coli	affects cotreatment, increases expression, decreases reaction	1
aceclofenac	decreases expression	1
N,N-diacetylcystine	decreases expression	1
tamibarotene	increases expression	1
quinupristin-dalfopristin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
lipopolysaccharide, E. coli O26-B6	decreases expression, decreases reaction	1
abrine	decreases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	increases expression, decreases reaction	1
Decitabine	increases expression	1
Zoledronic Acid	increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4264750	Binding	Inhibition of human L-selectin transfected in mouse 300.19 cells assessed as decrease in protein-mediated cell rolling on GlyCAM-1 or PNAd preincubated for 5 mins followed by cell perfusion through laminar flow chamber coated with GlyCAM-1	Chemistry-driven glycoscience. — Bioorg Med Chem

Clinical trials (associated diseases)

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