LY6S

Summary

LY6S (lymphocyte antigen 6 family member S, HGNC:54397) is a protein-coding gene on chromosome 8q24.3, encoding Lymphocyte antigen 6S (P0DTL4).

Predicted to enable acetylcholine receptor binding activity and acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to act upstream of or within response to bacterium. Predicted to be located in external side of plasma membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 105375795 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001406478

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:54397
Approved symbol	LY6S
Name	lymphocyte antigen 6 family member S
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	LY6A
Ensembl gene	ENSG00000291309
Ensembl biotype	protein_coding
Entrez	105375795

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000706920, ENST00000715543, ENST00000715551, ENST00000715552, ENST00000910865, ENST00000910866, ENST00000948536

RefSeq mRNA: 2 — MANE Select: NM_001406478 NM_001406477, NM_001406478

Canonical transcript exons

ENST00000706920 — 4 exons

Exon	Start	End
ENSE00003997452	143045573	143045710
ENSE00004027055	143044684	143044800
ENSE00004027056	143040839	143043338
ENSE00004027057	143045281	143045359

Expression profiles

Top tissues by expression

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

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6g	ENSMUSG00000022582
mus_musculus	Ly6f	ENSMUSG00000022583
mus_musculus	Ly6c2	ENSMUSG00000022584
mus_musculus	Ly6i	ENSMUSG00000022586
mus_musculus	Ly6g2	ENSMUSG00000047728
mus_musculus	Ly6a	ENSMUSG00000075602
mus_musculus	Ly6c1	ENSMUSG00000079018
rattus_norvegicus	Ly6i	ENSRNOG00000007137
rattus_norvegicus	Ly6cl1	ENSRNOG00000037375
rattus_norvegicus	Ly6al1	ENSRNOG00000048850
rattus_norvegicus	Ly6c	ENSRNOG00000061813

Paralogs (2): LY6H (ENSG00000176956), LY6L (ENSG00000261667)

Protein

Protein identifiers

Lymphocyte antigen 6S — P0DTL4 (reviewed: P0DTL4)

All UniProt accessions (2): P0DTL4, A0AAQ5BIF1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

RefSeq proteins (2): NP_001393406, NP_001393407* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR018363	CD59_antigen_CS	Conserved_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR051445	LY6H/LY6L_nAChR_modulators	Family

Pfam: PF00021

UniProt features (9 total): disulfide bond 4, signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DTL4-F1	77.65	0.20

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 (1): 105

Disulfide bonds (4): 29–53, 32–41, 76–98, 99–104

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_ACETYLCHOLINE, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_SYNAPSE, GOCC_SIDE_OF_MEMBRANE, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, GOMF_SIGNALING_RECEPTOR_INHIBITOR_ACTIVITY, chr8q24, GOBP_POSTSYNAPTIC_SIGNAL_TRANSDUCTION, GOMF_ACETYLCHOLINE_RECEPTOR_INHIBITOR_ACTIVITY

GO Biological Process (1): acetylcholine receptor signaling pathway (GO:0095500)

GO Molecular Function (2): acetylcholine receptor inhibitor activity (GO:0030550), acetylcholine receptor binding (GO:0033130)

GO Cellular Component (4): plasma membrane (GO:0005886), synapse (GO:0045202), side of membrane (GO:0098552), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acetylcholine receptor activity	2
membrane	2
cellular anatomical structure	2
postsynaptic signal transduction	1
cellular response to acetylcholine	1
signaling receptor inhibitor activity	1
acetylcholine receptor regulator activity	1
signaling receptor binding	1
cell periphery	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0JNB3, A0JNL5, A6NC86, H3BJG9, H3BQJ8, O55186, O94772, O95867, P05533, P0CW02, P0CW03, P0DTL4, P13987, P35456, P35459, P35460, P35461, P46657, P47777, P49616, P57096, P58019, Q03405, Q05588, Q14210, Q148C3, Q28216, Q28785, Q32PB3, Q4R5M8, Q5R510, Q63317, Q64253, Q6UWN5, Q6UX82, Q80ZQ0, Q8K1T6, Q8SQ46, Q8TDM5, Q924B5

Diamond homologs: A0JNB3, O94772, P0DTL4, Q16553, Q4R5M8, Q63317, Q90986, Q9WU67, Q9WUC3, H3BJG9, P05533, P0CW02, P0CW03, P35460, P35461, P0DP59

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000373376 (8:143043728 T>C,G), RS1001771808 (8:143043964 C>G,T), RS1002766677 (8:143045191 G>A,C,T), RS1003265051 (8:143046707 G>A), RS1003717041 (8:143046393 T>C), RS1004320560 (8:143044544 A>AC), RS1004393967 (8:143044328 G>A), RS1005116199 (8:143046481 G>C), RS1005666566 (8:143043598 C>T), RS1006956150 (8:143042851 G>T), RS1007726080 (8:143047247 C>T), RS1008255486 (8:143047062 A>G), RS10086405 (8:143045335 C>A), RS1009008715 (8:143046199 T>G), RS1009446966 (8:143043104 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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