LY6G6D

Summary

LY6G6D (lymphocyte antigen 6 family member G6D, HGNC:13935) is a protein-coding gene on chromosome 6p21.33, encoding Lymphocyte antigen 6 complex locus protein G6d (O95868).

LY6G6D belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).

Source: NCBI Gene 58530 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_021246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13935
Approved symbol	LY6G6D
Name	lymphocyte antigen 6 family member G6D
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	MEGT1, Ly6-D, G6D, LY6-D, NG25
Ensembl gene	ENSG00000244355
Ensembl biotype	protein_coding
OMIM	606038
Entrez	58530

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000375824, ENST00000375825, ENST00000479334

RefSeq mRNA: 1 — MANE Select: NM_021246 NM_021246

CCDS: CCDS34404

Canonical transcript exons

ENST00000375825 — 3 exons

Exon	Start	End
ENSE00003485143	31717581	31717919
ENSE00003668344	31715502	31715624
ENSE00003927671	31715348	31715410

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 94.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1353 / max 92.2264, expressed in 30 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67028	0.0690	21
67029	0.0473	16
67027	0.0457	10
67026	0.0206	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.36	gold quality
ganglionic eminence	UBERON:0004023	70.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	68.15	gold quality
prostate gland	UBERON:0002367	65.46	gold quality
skin of abdomen	UBERON:0001416	64.76	gold quality
zone of skin	UBERON:0000014	63.66	gold quality
skin of leg	UBERON:0001511	63.24	gold quality
ectocervix	UBERON:0012249	60.06	gold quality
granulocyte	CL:0000094	58.43	gold quality
rectum	UBERON:0001052	56.75	gold quality
vagina	UBERON:0000996	55.70	gold quality
placenta	UBERON:0001987	55.41	gold quality
colon	UBERON:0001155	54.21	gold quality
lower esophagus mucosa	UBERON:0035834	53.84	gold quality
uterine cervix	UBERON:0000002	53.53	gold quality
leukocyte	CL:0000738	52.96	gold quality
monocyte	CL:0000576	52.70	gold quality
ventricular zone	UBERON:0003053	52.23	gold quality
endocervix	UBERON:0000458	50.47	gold quality
left uterine tube	UBERON:0001303	50.45	gold quality
colonic epithelium	UBERON:0000397	47.62	gold quality
right lung	UBERON:0002167	47.38	gold quality
intestine	UBERON:0000160	46.59	gold quality
caudate nucleus	UBERON:0001873	46.00	gold quality
nucleus accumbens	UBERON:0001882	46.00	gold quality
transverse colon	UBERON:0001157	45.61	gold quality
esophagus mucosa	UBERON:0002469	45.36	gold quality
anterior cingulate cortex	UBERON:0009835	45.10	gold quality
fallopian tube	UBERON:0003889	44.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• Frequencies of the DRB1, DQA1, DQB1 and TNFA alleles in immigrant population of West Siberia (PMID:19807019)
• Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human microsatellite-stable colorectal cancers (PMID:30670049)
• LY6G6D is a selectively expressed colorectal cancer antigen that can be used for targeting a therapeutic T-cell response by a T-cell engager. (PMID:36159851)
• Decoding LY6G6D in colorectal cancer: Unraveling biomarker potential and therapeutic insights. (PMID:38836687)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6g6d	ENSMUSG00000073413
rattus_norvegicus	Ly6g6d	ENSRNOG00000027225

Paralogs (1): LY6G6F (ENSG00000204424)

Protein

Protein identifiers

Lymphocyte antigen 6 complex locus protein G6d — O95868 (reviewed: O95868)

Alternative names: Megakaryocyte-enhanced gene transcript 1 protein

All UniProt accessions (4): A0A1L6Z9X4, F6XWZ1, O95868, Q8NDY2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Cell projection. Filopodium.

Tissue specificity. Expressed in the adult lung, and in fetal liver, lung, kidney, brain and spleen.

Post-translational modifications. O-glycosylated.

RefSeq proteins (1): NP_067069* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR026524	LY6G6d/LY6G6f	Family

Pfam: PF00021

UniProt features (13 total): disulfide bond 3, sequence variant 2, glycosylation site 2, signal peptide 1, chain 1, turn 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7S4G	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95868-F1	66.50	0.00

Antibody-complex structures (SAbDab): 1 — 7S4G

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): 104

Disulfide bonds (3): 27–35, 42–71, 77–96

Glycosylation sites (2): 40, 41

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: 68 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOCC_CELL_SURFACE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, TGANTCA_AP1_C, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_ACETYLCHOLINE, NKX25_01, GOCC_FILOPODIUM, GOCC_SYNAPSE, GOCC_SIDE_OF_MEMBRANE

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

GO Molecular Function (3): acetylcholine receptor inhibitor activity (GO:0030550), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), filopodium (GO:0030175), protein-containing complex (GO:0032991), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995), 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
acetylcholine receptor activity	2
membrane	2
postsynaptic signal transduction	1
cellular response to acetylcholine	1
signaling receptor inhibitor activity	1
acetylcholine receptor regulator activity	1
protein binding	1
binding	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
actin-based cell projection	1
cellular_component	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY6G6D	LY6G6C	O95867	608
LY6G6D	A0A0B4J1T7	A0A0B4J1T7	581
LY6G6D	LY6G6F	Q5SQ64	512
LY6G6D	MPIG6B	O95866	478
LY6G6D	LY6G5B	Q8NDX9	475
LY6G6D	LY6L	H3BQJ8	446
LY6G6D	PATE3	B3GLJ2	431
LY6G6D	G6PD	P11413	396
LY6G6D	PINLYP	A6NC86	391
LY6G6D	DDAH2	O95865	380
LY6G6D	PATE2	Q6UY27	370
LY6G6D	LY6G5C	Q5SRR4	370
LY6G6D	PATE4	P0C8F1	351
LY6G6D	LYPD5	Q6UWN5	351
LY6G6D	PATE1	Q8WXA2	348

IntAct

15 interactions, top by confidence:

A	B	Type	Score
NCS1	LY6G6D	psi-mi:“MI:0915”(physical association)	0.560
NCALD	LY6G6D	psi-mi:“MI:0915”(physical association)	0.560
UBQLN2	LY6G6D	psi-mi:“MI:0915”(physical association)	0.560
LY6G6D	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
LY6G6D	NCS1	psi-mi:“MI:0915”(physical association)	0.560
LY6G6D	NCALD	psi-mi:“MI:0915”(physical association)	0.560
LY6G6D	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
LY6G6D	HSPA5	psi-mi:“MI:0915”(physical association)	0.500
LY6G6D	HSPA5	psi-mi:“MI:0914”(association)	0.500
LY6G6D	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): LY6G6D (Two-hybrid), LY6G6D (Two-hybrid), LY6G6D (Two-hybrid), LY6G6D (Two-hybrid), HSPA5 (Affinity Capture-MS), RNF139 (Affinity Capture-MS), FAM8A1 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS)

ESM2 similar proteins: A0MLS4, A2BDG0, A2BDG5, A2BDG9, A2RRL7, A3KN25, A6NGB7, G1TZA0, O14669, O77751, O77801, O95868, P01286, P02820, P02822, P0DUJ6, P24807, P25063, P27177, P41547, P51460, P63292, P98162, Q01524, Q08DF2, Q1ECT8, Q1JPW9, Q496H8, Q58CU5, Q5CZK3, Q5G860, Q5G863, Q5HZE8, Q60549, Q64697, Q6BEG6, Q7TPG6, Q8C4W3, Q8R182, Q923S2

Diamond homologs: O95868, Q6MG58, Q9Z1Q3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

848 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31715516:T:C	C24R	0.727
6:31715516:T:A	C24S	0.715
6:31715517:G:C	C24S	0.715
6:31717706:T:A	C102S	0.694
6:31717707:G:C	C102S	0.694
6:31715386:A:C	S11R	0.685
6:31715388:C:A	S11R	0.685
6:31715388:C:G	S11R	0.685
6:31715518:C:G	C24W	0.684
6:31717708:C:G	C102W	0.665
6:31717615:C:G	C71W	0.658
6:31717613:T:C	C71R	0.637
6:31717633:C:G	C77W	0.636
6:31717690:C:G	C96W	0.633
6:31717711:C:A	N103K	0.632
6:31717711:C:G	N103K	0.632
6:31717761:C:A	A120D	0.627
6:31715570:T:C	C42R	0.623
6:31717767:C:A	A122D	0.619
6:31715549:T:C	C35R	0.617
6:31715572:T:G	C42W	0.612
6:31717707:G:A	C102Y	0.608
6:31715551:C:G	C35W	0.606
6:31715378:T:C	I8T	0.603
6:31715410:G:A	G19R	0.601
6:31715410:G:C	G19R	0.601
6:31717706:T:C	C102R	0.600
6:31715549:T:A	C35S	0.599
6:31715550:G:C	C35S	0.599
6:31717613:T:A	C71S	0.596

dbSNP variants (sampled 300 via entrez): RS1000519301 (6:31716282 A>G), RS1000553362 (6:31715747 A>C,T), RS1002221010 (6:31718033 T>C,G), RS1003138464 (6:31713452 A>G), RS1004125259 (6:31713802 G>A), RS1004126247 (6:31716747 C>T), RS1005769496 (6:31714914 G>T), RS1007377203 (6:31716977 G>A), RS1010240611 (6:31713495 G>A), RS1013569096 (6:31717508 C>T), RS1013615332 (6:31717101 T>A), RS1014006780 (6:31716843 C>T), RS1014121082 (6:31717969 G>A), RS1015405202 (6:31713370 A>G), RS1016608492 (6:31714822 A>G)

Disease associations

OMIM: gene MIM:606038 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	increases methylation	1
Fluorouracil	affects response to substance	1
Triclosan	increases expression	1
Tunicamycin	decreases expression	1
Antirheumatic Agents	decreases expression	1
Thapsigargin	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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