LY6D

Summary

LY6D (lymphocyte antigen 6 family member D, HGNC:13348) is a protein-coding gene on chromosome 8q24.3, encoding Lymphocyte antigen 6D (Q14210). May act as a specification marker at earliest stage specification of lymphocytes between B- and T-cell development.

Predicted to be involved in lymphocyte differentiation. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in cell surface.

Source: NCBI Gene 8581 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_003695

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13348
Approved symbol	LY6D
Name	lymphocyte antigen 6 family member D
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	E48
Ensembl gene	ENSG00000167656
Ensembl biotype	protein_coding
OMIM	606204
Entrez	8581

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000301263, ENST00000518434, ENST00000518469, ENST00000518884

RefSeq mRNA: 1 — MANE Select: NM_003695 NM_003695

CCDS: CCDS6390

Canonical transcript exons

ENST00000301263 — 3 exons

Exon	Start	End
ENSE00001115344	142785589	142785687
ENSE00001236093	142786465	142786539
ENSE00002127930	142784882	142785456

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 99.73.

FANTOM5 (CAGE): breadth broad, TPM avg 9.8296 / max 2297.1670, expressed in 220 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95433	9.7417	212
95432	0.0879	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.73	gold quality
gingiva	UBERON:0001828	99.58	gold quality
pharyngeal mucosa	UBERON:0000355	99.52	gold quality
gingival epithelium	UBERON:0001949	99.52	gold quality
tongue squamous epithelium	UBERON:0006919	99.24	gold quality
oral cavity	UBERON:0000167	99.17	gold quality
esophagus mucosa	UBERON:0002469	99.12	gold quality
skin of abdomen	UBERON:0001416	98.93	gold quality
skin of leg	UBERON:0001511	98.87	gold quality
body of tongue	UBERON:0011876	98.87	gold quality
zone of skin	UBERON:0000014	98.51	gold quality
mammalian vulva	UBERON:0000997	98.32	gold quality
penis	UBERON:0000989	98.11	gold quality
upper leg skin	UBERON:0004262	97.96	gold quality
cervix epithelium	UBERON:0004801	97.72	gold quality
right adrenal gland cortex	UBERON:0035827	97.68	gold quality
skin of hip	UBERON:0001554	97.40	gold quality
upper arm skin	UBERON:0004263	97.25	gold quality
squamous epithelium	UBERON:0006914	97.22	gold quality
nipple	UBERON:0002030	97.20	gold quality
esophagus squamous epithelium	UBERON:0006920	96.55	gold quality
epithelium of esophagus	UBERON:0001976	96.42	gold quality
cervix squamous epithelium	UBERON:0006922	95.55	silver quality
right adrenal gland	UBERON:0001233	94.77	gold quality
tongue	UBERON:0001723	94.10	gold quality
left adrenal gland cortex	UBERON:0035825	93.42	gold quality
left adrenal gland	UBERON:0001234	93.36	gold quality
vagina	UBERON:0000996	93.22	gold quality
adrenal cortex	UBERON:0001235	92.31	gold quality
nasal cavity epithelium	UBERON:0005384	90.82	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	5823.69
E-MTAB-8142	yes	3465.63
E-CURD-114	yes	2823.95
E-CURD-11	no	103.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting LY6D, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-4445-3P	93.28	66.18	106
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 8)

• induction of LY6D expression is triggered through a pathway regulated by ATM, CHK2 and p53 (PMID:23075424)
• E48 expression was strong and diffuse in non-neoplastic squamous epithelium, and decreased with progression to laryngeal squamous cell carcinoma. Poorly differentiated tumors had fewer E48-positive cells than well- to moderately- differentiated cases. (PMID:23672314)
• LY6D is the most highly up-regulated in HTR-8/SVneo-SP cells and it has potential to maintain cell proliferation of the cells. it is important for the maintenance of the cells. (PMID:26223706)
• Study results suggest that OLFM4, LY6D and S100A7 immunoreactivity are associated with an aggressive phenotype of estrogen receptor (ER)-positive breast carcinoma, and these are potent markers for distant metastasis of ER-positive breast cancer patients. (PMID:30137688)
• LY6D may serve as a prognostic maker for advanced prostate cancer. (PMID:30566873)
• LY6D-induced macropinocytosis as a survival mechanism of senescent cells. (PMID:33168631)
• Investigation of Candidate Genes and Pathways in Basal/TNBC Patients by Integrated Analysis. (PMID:34184566)
• Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells’ Proliferation, Stemness, Invasion, and Apoptosis via the MAPK Pathway. (PMID:38067506)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6d	ENSMUSG00000034634
rattus_norvegicus	Ly6d	ENSRNOG00000026133
caenorhabditis_elegans	D1081.20	WBGENE00304985

Paralogs (1): LYNX1 (ENSG00000180155)

Protein

Protein identifiers

Lymphocyte antigen 6D — Q14210 (reviewed: Q14210)

Alternative names: E48 antigen

All UniProt accessions (1): Q14210

UniProt curated annotations — full annotation on UniProt →

Function. May act as a specification marker at earliest stage specification of lymphocytes between B- and T-cell development. Marks the earliest stage of B-cell specification.

Subcellular location. Cell membrane.

Tissue specificity. Expressed exclusively at the outer cell surface of transitional epithelia and the keratinocyte of stratified squamous epithelia.

RefSeq proteins (1): NP_003686* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR018363	CD59_antigen_CS	Conserved_site
IPR035076	Toxin/TOLIP	Domain
IPR042339	Ly6D	Family
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00087

UniProt features (13 total): disulfide bond 5, sequence conflict 2, signal peptide 1, chain 1, sequence variant 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-Q14210-F1	79.78	0.43

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): 98

Disulfide bonds (5): 23–45, 26–32, 38–63, 67–86, 87–92

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 169 (showing top): AP1_01, JAEGER_METASTASIS_DN, PEREZ_TP63_TARGETS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOCC_CELL_SURFACE, MORI_IMMATURE_B_LYMPHOCYTE_UP, MCBRYAN_TERMINAL_END_BUD_UP, BORLAK_LIVER_CANCER_EGF_UP, MARTINEZ_RB1_TARGETS_UP, RICKMAN_METASTASIS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP

GO Biological Process (3): cell adhesion (GO:0007155), lymphocyte differentiation (GO:0030098), response to stilbenoid (GO:0035634)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
cellular process	1
lymphocyte activation	1
mononuclear cell differentiation	1
response to chemical	1
binding	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY6D	CD59	P13987	671
LY6D	SLURP1	P55000	470
LY6D	LY6K	Q17RY6	436
LY6D	KRT84	Q9NSB2	413
LY6D	G0S2	P27469	409
LY6D	FABP1	P07148	406
LY6D	FGB	P02675	406
LY6D	PSCA	O43653	397
LY6D	ONECUT1	Q9UBC0	391
LY6D	LYPD2	Q6UXB3	385
LY6D	KRT36	O76013	381
LY6D	FAM216A	Q8WUB2	374
LY6D	MAL	P21145	372
LY6D	TRIM29	Q14134	372
LY6D	SLC25A25	Q6KCM7	370

IntAct

20 interactions, top by confidence:

A	B	Type	Score
	LY6D	psi-mi:“MI:0915”(physical association)	0.560
AQP6	LY6D	psi-mi:“MI:0915”(physical association)	0.560
LY6D	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
LY6D	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
LY6D	GRB2	psi-mi:“MI:0915”(physical association)	0.400
PA	LY6D	psi-mi:“MI:0915”(physical association)	0.370
LY6D	PKIB	psi-mi:“MI:0915”(physical association)	0.370
ABCB11	LY6D	psi-mi:“MI:0915”(physical association)	0.370
LY6D	ARFIP2	psi-mi:“MI:0915”(physical association)	0.370
LY6D	GRIN2A	psi-mi:“MI:0914”(association)	0.350
LY6D	STX7	psi-mi:“MI:0914”(association)	0.350
LY6D		psi-mi:“MI:0915”(physical association)	0.000
LY6D	AQP6	psi-mi:“MI:0915”(physical association)	0.000
LY6D	ELOVL4	psi-mi:“MI:0915”(physical association)	0.000
LY6D	TMEM86B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): LY6D (Affinity Capture-MS), LY6D (Two-hybrid), LY6D (Two-hybrid), TMEM31 (Two-hybrid), TMEM86B (Two-hybrid), MCOLN1 (Affinity Capture-MS), GRIN2A (Affinity Capture-MS), MCOLN2 (Affinity Capture-MS), CTNNAL1 (Affinity Capture-MS), HIST2H2AB (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS), VIM (Affinity Capture-MS), STX7 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), LY6D (Affinity Capture-MS)

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: P35459, Q14210, Q148C3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

345 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142785452:CTCCA:C	acceptor_gain	1.0000
8:142785454:CCA:C	acceptor_gain	1.0000
8:142785455:CAC:C	acceptor_gain	1.0000
8:142785457:C:CC	acceptor_gain	1.0000
8:142785453:TCCA:T	acceptor_gain	0.9900
8:142785453:TCCAC:T	acceptor_loss	0.9900
8:142785454:CCAC:C	acceptor_gain	0.9900
8:142785454:CCACT:C	acceptor_loss	0.9900
8:142785455:C:T	acceptor_gain	0.9900
8:142785455:CA:C	acceptor_gain	0.9900
8:142785456:ACTGG:A	acceptor_loss	0.9900
8:142785457:CTGGG:C	acceptor_loss	0.9900
8:142785585:CCA:C	donor_loss	0.9900
8:142785588:C:CT	donor_loss	0.9900
8:142785688:C:CC	acceptor_gain	0.9900
8:142786459:CCTCA:C	donor_loss	0.9900
8:142786460:CTCA:C	donor_loss	0.9900
8:142786461:TCA:T	donor_loss	0.9900
8:142786462:CA:C	donor_loss	0.9900
8:142786463:A:AT	donor_loss	0.9900
8:142786464:C:A	donor_loss	0.9900
8:142785458:T:A	acceptor_loss	0.9800
8:142785585:CCACC:C	donor_gain	0.9800
8:142785684:AGGG:A	acceptor_gain	0.9800
8:142785711:A:T	acceptor_gain	0.9700
8:142785587:A:AC	donor_gain	0.9600
8:142785588:C:CC	donor_gain	0.9600
8:142785685:GGG:G	acceptor_gain	0.9600
8:142785462:C:CT	acceptor_gain	0.9500
8:142785683:AAGGG:A	acceptor_gain	0.9500

AlphaMissense

819 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142785425:C:A	K61N	0.993
8:142785425:C:G	K61N	0.993
8:142785606:C:G	C45S	0.993
8:142785607:A:T	C45S	0.993
8:142785672:C:G	C23S	0.991
8:142785673:A:T	C23S	0.991
8:142785606:C:T	C45Y	0.990
8:142785329:A:C	N93K	0.989
8:142785329:A:T	N93K	0.989
8:142785333:C:G	C92S	0.988
8:142785334:A:T	C92S	0.988
8:142785408:C:G	C67S	0.985
8:142785409:A:T	C67S	0.985
8:142785427:T:C	K61E	0.984
8:142785351:C:G	C86S	0.983
8:142785352:A:T	C86S	0.983
8:142785420:C:G	C63S	0.983
8:142785421:A:T	C63S	0.983
8:142785663:C:G	C26S	0.983
8:142785664:A:T	C26S	0.983
8:142785348:C:G	C87S	0.982
8:142785349:A:T	C87S	0.982
8:142785426:T:G	K61T	0.981
8:142785608:G:C	F44L	0.981
8:142785608:G:T	F44L	0.981
8:142785610:A:G	F44L	0.981
8:142785409:A:G	C67R	0.980
8:142785605:G:C	C45W	0.980
8:142785606:C:A	C45F	0.980
8:142785607:A:G	C45R	0.980

dbSNP variants (sampled 300 via entrez): RS1000890224 (8:142784508 C>T), RS1000946080 (8:142787700 C>T), RS1001495164 (8:142785701 A>G), RS1003763494 (8:142786721 G>A,T), RS1003836444 (8:142786583 G>A,C), RS1004259149 (8:142784431 T>C,G), RS1004793392 (8:142787661 G>A,C), RS1004804747 (8:142787522 C>A,T), RS1005094924 (8:142787742 C>T), RS1005334501 (8:142785313 C>T), RS1005611735 (8:142785141 C>T), RS1006597003 (8:142786060 C>G,T), RS1007541987 (8:142786064 G>C), RS1008092401 (8:142786361 G>A,C,T), RS1008200828 (8:142787902 A>G,T)

Disease associations

OMIM: gene MIM:606204 | 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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
lasiocarpine	increases expression	1
propionaldehyde	increases expression	1
chlortoluron	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
enilconazole	decreases expression	1
corosolic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Arsenicals	increases expression	1
Cannabidiol	decreases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	decreases expression	1
Furaldehyde	affects localization, decreases expression, increases expression, affects cotreatment	1
Lead	affects methylation	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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