LY6G6C

Summary

LY6G6C (lymphocyte antigen 6 family member G6C, HGNC:13936) is a protein-coding gene on chromosome 6p21.33, encoding Lymphocyte antigen 6 complex locus protein G6c (O95867).

LY6G6C 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 80740 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_025261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13936
Approved symbol	LY6G6C
Name	lymphocyte antigen 6 family member G6C
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	G6c, NG24
Ensembl gene	ENSG00000204421
Ensembl biotype	protein_coding
OMIM	610435
Entrez	80740

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000375819, ENST00000495859

RefSeq mRNA: 1 — MANE Select: NM_025261 NM_025261

CCDS: CCDS4714

Canonical transcript exons

ENST00000375819 — 3 exons

Exon	Start	End
ENSE00001885397	31721628	31721746
ENSE00003541954	31718648	31719310
ENSE00003547550	31720093	31720203

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 98.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4988 / max 807.0679, expressed in 93 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72797	1.4819	91
72798	0.0168	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	98.96	gold quality
lower esophagus mucosa	UBERON:0035834	98.74	gold quality
zone of skin	UBERON:0000014	98.71	gold quality
skin of leg	UBERON:0001511	98.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.22	silver quality
esophagus mucosa	UBERON:0002469	85.14	gold quality
placenta	UBERON:0001987	82.11	gold quality
vagina	UBERON:0000996	79.44	gold quality
esophagus	UBERON:0001043	70.42	gold quality
ectocervix	UBERON:0012249	70.33	gold quality
ganglionic eminence	UBERON:0004023	65.62	gold quality
tonsil	UBERON:0002372	64.57	gold quality
uterine cervix	UBERON:0000002	63.69	gold quality
fallopian tube	UBERON:0003889	63.34	gold quality
blood	UBERON:0000178	63.00	gold quality
omental fat pad	UBERON:0010414	62.77	gold quality
minor salivary gland	UBERON:0001830	61.22	gold quality
popliteal artery	UBERON:0002250	60.99	gold quality
tibial artery	UBERON:0007610	60.95	gold quality
granulocyte	CL:0000094	60.58	gold quality
left uterine tube	UBERON:0001303	60.27	gold quality
right lung	UBERON:0002167	60.12	gold quality
nucleus accumbens	UBERON:0001882	59.75	gold quality
saliva-secreting gland	UBERON:0001044	59.17	gold quality
mucosa of stomach	UBERON:0001199	58.86	gold quality
ascending aorta	UBERON:0001496	58.84	gold quality
thoracic aorta	UBERON:0001515	58.60	gold quality
adipose tissue	UBERON:0001013	58.42	gold quality
descending thoracic aorta	UBERON:0002345	58.04	gold quality
multicellular organism	UBERON:0000468	57.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	87.07
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting LY6G6C, 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-4533	100.00	69.48	2758
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6g6c	ENSMUSG00000092586
rattus_norvegicus	Ly6g6c	ENSRNOG00000070605

Protein

Protein identifiers

Lymphocyte antigen 6 complex locus protein G6c — O95867 (reviewed: O95867)

All UniProt accessions (3): A0A1U9X7Z1, G3V1A8, O95867

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Monomer.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed at the leading edges of cells, on filopodia.

Post-translational modifications. N-glycosylated.

RefSeq proteins (1): NP_079537* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR039237	LY6G6C	Family
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00021

UniProt features (11 total): disulfide bond 4, signal peptide 1, chain 1, sequence variant 1, propeptide 1, domain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95867-F1	84.90	0.58

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): 99

Disulfide bonds (4): 22–47, 25–33, 39–65, 92–97

Glycosylation sites (1): 88

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: 83 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, MODULE_52, YAGI_AML_WITH_INV_16_TRANSLOCATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOCC_CELL_SURFACE, GGGTGGRR_PAX4_03, BACH2_01, CAR_MYST2, TGANTCA_AP1_C, MODULE_88, MODULE_18, MODULE_60, MODULE_95, MODULE_38

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), side of membrane (GO:0098552), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

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	3
membrane	2
protein binding	1
binding	1
cell periphery	1
cellular_component	1
leaflet of membrane bilayer	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY6G6C	LY6G5C	Q5SRR4	796
LY6G6C	A0A0B4J1T7	A0A0B4J1T7	719
LY6G6C	LY6G5B	Q8NDX9	695
LY6G6C	LY6G6F	Q5SQ64	668
LY6G6C	LY6G6D	O95868	608
LY6G6C	LY6L	H3BQJ8	603
LY6G6C	PATE3	B3GLJ2	593
LY6G6C	MPIG6B	O95866	581
LY6G6C	PINLYP	A6NC86	571
LY6G6C	VWA7	Q9Y334	570
LY6G6C	PATE2	Q6UY27	541
LY6G6C	PATE1	Q8WXA2	507
LY6G6C	DDAH2	O95865	507
LY6G6C	PATE4	P0C8F1	507
LY6G6C	LYPD5	Q6UWN5	507

IntAct

26 interactions, top by confidence:

A	B	Type	Score
SLC39A2	LY6G6C	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	SLC39A2	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	ARLN	psi-mi:“MI:0915”(physical association)	0.560
LY6G6C	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC17	LY6G6C	psi-mi:“MI:0915”(physical association)	0.370
CCDC82	LY6G6C	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
ZC3HC1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
UBE2J1	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000
YIPF6	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000
SLC41A2	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000
ARLN	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000
SLC38A7	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000
TMEM203	LY6G6C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): LY6G6C (Two-hybrid), LY6G6C (Affinity Capture-MS), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Two-hybrid), LY6G6C (Affinity Capture-MS), LY6G6C (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: A0JNL5, O95867, Q9Z1Q4

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	15
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

634 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31719310:CCT:C	acceptor_loss	1.0000
6:31719306:CTTAC:C	acceptor_gain	0.9900
6:31719312:T:A	acceptor_loss	0.9900
6:31720200:TCAG:T	acceptor_gain	0.9900
6:31720201:CAG:C	acceptor_gain	0.9900
6:31720201:CAGC:C	acceptor_gain	0.9900
6:31720204:C:CC	acceptor_gain	0.9900
6:31719283:C:CT	acceptor_gain	0.9800
6:31719307:TTAC:T	acceptor_gain	0.9800
6:31720202:A:T	acceptor_gain	0.9800
6:31720360:A:C	acceptor_gain	0.9800
6:31719285:C:CT	acceptor_gain	0.9700
6:31719308:TAC:T	acceptor_gain	0.9700
6:31719311:C:CC	acceptor_gain	0.9700
6:31719317:G:C	acceptor_gain	0.9700
6:31720087:TGTTA:T	donor_loss	0.9700
6:31720088:GTTA:G	donor_loss	0.9700
6:31720089:TTA:T	donor_loss	0.9700
6:31720090:TA:T	donor_loss	0.9700
6:31720091:ACC:A	donor_loss	0.9700
6:31720092:C:G	donor_loss	0.9700
6:31720199:GTCAG:G	acceptor_gain	0.9700
6:31720201:CAGCT:C	acceptor_loss	0.9700
6:31720204:CTG:C	acceptor_loss	0.9700
6:31720205:T:C	acceptor_loss	0.9700
6:31720086:ATGTT:A	donor_loss	0.9600
6:31720176:T:C	acceptor_gain	0.9600
6:31720333:GTCT:G	acceptor_gain	0.9600
6:31720702:T:TA	donor_gain	0.9600
6:31719278:C:CT	acceptor_gain	0.9500

AlphaMissense

795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31719295:A:C	F60C	0.998
6:31719300:C:A	W58C	0.997
6:31719300:C:G	W58C	0.997
6:31720116:C:G	C47S	0.996
6:31720117:A:T	C47S	0.996
6:31719294:G:C	F60L	0.995
6:31719294:G:T	F60L	0.995
6:31719296:A:G	F60L	0.995
6:31719280:C:G	C65S	0.994
6:31719281:A:T	C65S	0.994
6:31719295:A:G	F60S	0.993
6:31720117:A:G	C47R	0.992
6:31720191:C:G	C22S	0.991
6:31720192:A:T	C22S	0.991
6:31719259:C:G	C72S	0.990
6:31719260:A:T	C72S	0.990
6:31719293:A:G	S61P	0.990
6:31720115:G:C	C47W	0.990
6:31720159:A:G	C33R	0.990
6:31719184:C:G	C97S	0.989
6:31719185:A:T	C97S	0.989
6:31719286:A:G	L63P	0.989
6:31719184:C:T	C97Y	0.988
6:31719281:A:G	C65R	0.988
6:31719183:G:C	C97W	0.987
6:31719199:C:G	C92S	0.987
6:31719200:A:T	C92S	0.987
6:31720158:C:G	C33S	0.987
6:31720159:A:T	C33S	0.987
6:31720192:A:G	C22R	0.987

dbSNP variants (sampled 300 via entrez): RS1001126146 (6:31722750 G>A), RS1001157311 (6:31723065 C>T), RS1001185679 (6:31720088 G>A), RS1001215235 (6:31719657 C>T), RS1002799794 (6:31720944 T>C), RS1002830985 (6:31721229 C>T), RS1003265724 (6:31722061 G>A), RS1004559033 (6:31722240 A>T), RS1004934858 (6:31719283 C>A,T), RS1005171854 (6:31723107 T>C), RS1005265539 (6:31723407 A>G), RS1006303290 (6:31720810 ATT>A), RS1006687221 (6:31721595 C>A,T), RS1007471536 (6:31720285 G>T), RS1008040705 (6:31720518 G>A)

Disease associations

OMIM: gene MIM:610435 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008810_42	Smoking initiation (ever regular vs never regular)	7.000000e-09
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010725_43	Malaria	5.000000e-07
GCST010725_62	Malaria	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Arsenic	increases abundance, decreases expression	1
Cadmium	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Fluorouracil	affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Asbestos, Crocidolite	increases expression	1
Sodium Selenite	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases methylation	1

Clinical trials (associated diseases)

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