LY6H

Summary

LY6H (lymphocyte antigen 6 family member H, HGNC:6728) is a protein-coding gene on chromosome 8q24.3, encoding Lymphocyte antigen 6H (O94772). Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity.

Predicted to enable acetylcholine receptor binding activity and acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to be located in extracellular region. Predicted to be active in plasma membrane.

Source: NCBI Gene 4062 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_001135655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6728
Approved symbol	LY6H
Name	lymphocyte antigen 6 family member H
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	NMLY6
Ensembl gene	ENSG00000176956
Ensembl biotype	protein_coding
OMIM	603625
Entrez	4062

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000342752, ENST00000414417, ENST00000430474, ENST00000479685, ENST00000615409

RefSeq mRNA: 3 — MANE Select: NM_001135655 NM_001130478, NM_001135655, NM_002347

CCDS: CCDS47926, CCDS6396

Canonical transcript exons

ENST00000342752 — 4 exons

Exon	Start	End
ENSE00001273918	143158803	143158922
ENSE00001912943	143160198	143160321
ENSE00003463618	143159582	143159709
ENSE00003905899	143157916	143158485

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 98.94.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3226 / max 302.0733, expressed in 259 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95447	3.3981	238
95448	0.3843	147
95444	0.3460	127
95443	0.0856	46
95445	0.0711	49
95446	0.0375	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Ammon’s horn	UBERON:0001954	98.94	gold quality
temporal lobe	UBERON:0001871	98.78	gold quality
amygdala	UBERON:0001876	98.77	gold quality
hypothalamus	UBERON:0001898	98.63	gold quality
anterior cingulate cortex	UBERON:0009835	98.38	gold quality
superior frontal gyrus	UBERON:0002661	98.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.24	gold quality
cerebral cortex	UBERON:0000956	97.93	gold quality
prefrontal cortex	UBERON:0000451	97.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.89	gold quality
nucleus accumbens	UBERON:0001882	97.78	gold quality
frontal cortex	UBERON:0001870	97.52	gold quality
right frontal lobe	UBERON:0002810	96.93	gold quality
cortical plate	UBERON:0005343	96.76	gold quality
caudate nucleus	UBERON:0001873	95.75	gold quality
putamen	UBERON:0001874	95.26	gold quality
primary visual cortex	UBERON:0002436	95.23	gold quality
substantia nigra	UBERON:0002038	93.34	gold quality
ventricular zone	UBERON:0003053	92.94	gold quality
ganglionic eminence	UBERON:0004023	92.41	gold quality
brain	UBERON:0000955	91.91	gold quality
pituitary gland	UBERON:0000007	91.42	gold quality
adenohypophysis	UBERON:0002196	90.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.14	gold quality
right uterine tube	UBERON:0001302	80.90	gold quality
body of stomach	UBERON:0001161	78.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.20	gold quality
stomach	UBERON:0000945	76.18	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	404.18
E-MTAB-8381	yes	110.40
E-HCAD-5	yes	43.22
E-GEOD-93593	yes	16.99
E-MTAB-5061	yes	11.20
E-GEOD-81547	yes	8.03
E-GEOD-84465	yes	6.66
E-ANND-3	no	2.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting LY6H, 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-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-25-5P	87.02	64.95	84

Literature-anchored findings (GeneRIF, showing 1)

• Unbalanced Regulation of alpha7 nAChRs by Ly6h and NACHO Contributes to Neurotoxicity in Alzheimer’s Disease. (PMID:34446574)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly6h	ENSMUSG00000022577

Paralogs (2): LY6L (ENSG00000261667), LY6S (ENSG00000291309)

Protein

Protein identifiers

Lymphocyte antigen 6H — O94772 (reviewed: O94772)

All UniProt accessions (1): O94772

UniProt curated annotations — full annotation on UniProt →

Function. Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-3:beta-4-containing nAChRs maximum response. May play a role in the intracellular trafficking of alpha-7-containing nAChRs and may inhibit their expression at the cell surface. Seems to inhibit alpha-7/CHRNA7 signaling in hippocampal neurons.

Subunit / interactions. Interacts with CHRNA4 and CHRNA7.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in brain (cerebral cortex, amygdala, hippocampus and subthalamic nucleus) and in acute human leukemic cell line MOLT-3. Also found in lower levels in testis, pancreas, small intestine and colon.

Isoforms (2)

UniProt ID	Names	Canonical?
O94772-1	1	yes
O94772-2	2

RefSeq proteins (3): NP_001123950, NP_001129127, NP_002338 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00021

UniProt features (13 total): disulfide bond 5, signal peptide 1, chain 1, splice variant 1, sequence conflict 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-O94772-F1	76.28	0.26

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): 115

Disulfide bonds (5): 105–110, 28–52, 31–40, 45–73, 77–104

Glycosylation sites (1): 36

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: 97 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, MODULE_66, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, MODULE_75, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_ACETYLCHOLINE, GOMF_SIGNALING_RECEPTOR_BINDING, MODULE_11

GO Biological Process (3): nervous system development (GO:0007399), animal organ morphogenesis (GO:0009887), acetylcholine receptor signaling pathway (GO:0095500)

GO Molecular Function (3): acetylcholine receptor inhibitor activity (GO:0030550), acetylcholine receptor binding (GO:0033130), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), synapse (GO:0045202), side of membrane (GO:0098552), 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
acetylcholine receptor activity	2
membrane	2
system development	1
anatomical structure morphogenesis	1
animal organ development	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
signaling receptor inhibitor activity	1
acetylcholine receptor regulator activity	1
signaling receptor binding	1
binding	1
cell periphery	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY6H	LYNX1	P0DP58	806
LY6H	LY6K	Q17RY6	736
LY6H	SLURP1	P55000	719
LY6H	LYPD6	Q86Y78	712
LY6H	LYPD2	Q6UXB3	711
LY6H	LYPD4	Q6UWN0	645
LY6H	GPIHBP1	Q8IV16	627
LY6H	LYPD6B	Q8NI32	614
LY6H	PATE3	B3GLJ2	593
LY6H	PATE2	Q6UY27	570
LY6H	LYPD5	Q6UWN5	570
LY6H	SPACA4	Q8TDM5	548
LY6H	PATE4	P0C8F1	544
LY6H	PINLYP	A6NC86	543
LY6H	RIC3	Q7Z5B4	503

IntAct

12 interactions, top by confidence:

A	B	Type	Score
LY6H	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	LY6H	psi-mi:“MI:0915”(physical association)	0.560
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
LY6H	NXPH4	psi-mi:“MI:0914”(association)	0.350
LY6H	MGRN1	psi-mi:“MI:0914”(association)	0.350
DVL3	LY6H	psi-mi:“MI:0915”(physical association)	0.000
PPP1R16A	LY6H	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (57): LY6H (Two-hybrid), ZNF696 (Affinity Capture-MS), LRP11 (Affinity Capture-MS), ZNF664 (Affinity Capture-MS), TXNDC16 (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), MAEA (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), GDF11 (Affinity Capture-MS), RMND5A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), BCHE (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), GCNT1 (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: A0JNB3, O94772, P0DTL4, Q16553, Q4R5M8, Q63317, Q90986, Q9WU67, Q9WUC3, H3BJG9, P05533, P0CW02, P0CW03, P35460, P35461, O43653, Q64253, P0DP59

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

481 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143159578:TCACC:T	donor_loss	1.0000
8:143159579:CACC:C	donor_loss	1.0000
8:143159580:A:AC	donor_gain	1.0000
8:143159580:ACCG:A	donor_loss	1.0000
8:143159581:C:CC	donor_gain	1.0000
8:143159581:CCGGG:C	donor_gain	1.0000
8:143159851:T:TA	donor_gain	1.0000
8:143158801:A:AC	donor_gain	0.9900
8:143158802:C:CT	donor_gain	0.9900
8:143158802:CTG:C	donor_gain	0.9900
8:143159836:C:A	donor_gain	0.9900
8:143159840:T:TA	donor_gain	0.9900
8:143158802:CT:C	donor_gain	0.9800
8:143158802:CTGCT:C	donor_gain	0.9800
8:143158934:A:C	acceptor_gain	0.9800
8:143159576:A:AC	donor_gain	0.9800
8:143159577:C:CC	donor_gain	0.9800
8:143159580:AC:A	donor_gain	0.9800
8:143159581:CC:C	donor_gain	0.9800
8:143159581:CCG:C	donor_gain	0.9800
8:143159581:CCGG:C	donor_gain	0.9800
8:143159833:AGCC:A	donor_gain	0.9800
8:143159843:C:CA	donor_gain	0.9800
8:143159866:T:TA	donor_gain	0.9800
8:143159867:C:A	donor_gain	0.9800
8:143159962:T:TA	donor_gain	0.9800
8:143158371:TCG:T	donor_gain	0.9700
8:143158799:T:TC	donor_loss	0.9700
8:143158800:TA:T	donor_loss	0.9700
8:143158801:AC:A	donor_loss	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000033925 (8:143157424 G>C), RS1000058936 (8:143159450 T>C), RS1000515074 (8:143159247 C>A,G,T), RS1001145186 (8:143160403 G>A,C,T), RS1001312920 (8:143160864 G>A,C), RS1001371666 (8:143159650 C>A,T), RS1002582721 (8:143157989 C>G,T), RS1002856519 (8:143159872 C>A,G), RS1003381823 (8:143159604 G>A,C), RS1003860589 (8:143162566 A>G), RS1004211073 (8:143161953 C>G), RS1004536532 (8:143160474 C>G), RS1004765351 (8:143160819 C>T), RS1004914355 (8:143159203 C>A,T), RS1004968162 (8:143158957 C>T)

Disease associations

OMIM: gene MIM:603625 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002937_8	Molybdenum levels	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cytarabine	decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1562	NCI-H446	Cancer cell line	Male
CVCL_C1MD	H446/VP	Cancer cell line	Male
CVCL_E2Q8	HyCyte NCI-H446 hHFE_p.C282Y_c.845G>A	Cancer cell line	Male
CVCL_RT18	H446/EP	Cancer cell line	Male
CVCL_RT21	H446/CDDP	Cancer cell line	Male

Clinical trials (associated diseases)

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