LYPD1

Summary

LYPD1 (LY6/PLAUR domain containing 1, HGNC:28431) is a protein-coding gene on chromosome 2q21.2, encoding Ly6/PLAUR domain-containing protein 1 (Q8N2G4). Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity.

Predicted to enable acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to act upstream of or within several processes, including behavioral fear response; cholinergic synaptic transmission; and negative regulation of protein localization to plasma membrane. Predicted to be located in extracellular region and plasma membrane.

Source: NCBI Gene 116372 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_144586

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28431
Approved symbol	LYPD1
Name	LY6/PLAUR domain containing 1
Location	2q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC29643, PHTS
Ensembl gene	ENSG00000150551
Ensembl biotype	protein_coding
OMIM	610450
Entrez	116372

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000345008, ENST00000397463, ENST00000449209, ENST00000892683

RefSeq mRNA: 4 — MANE Select: NM_144586 NM_001077427, NM_001321234, NM_001321235, NM_144586

CCDS: CCDS42759, CCDS46416

Canonical transcript exons

ENST00000397463 — 3 exons

Exon	Start	End
ENSE00001384648	132643286	132646280
ENSE00001528793	132669881	132670205
ENSE00003691134	132668400	132668537

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 93.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4863 / max 336.0955, expressed in 951 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30702	16.2210	946
30703	0.1757	97
30704	0.0896	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.61	gold quality
nucleus accumbens	UBERON:0001882	90.66	gold quality
caudate nucleus	UBERON:0001873	88.18	gold quality
putamen	UBERON:0001874	86.08	gold quality
endometrium epithelium	UBERON:0004811	85.95	gold quality
ventricular zone	UBERON:0003053	85.84	gold quality
hypothalamus	UBERON:0001898	85.79	gold quality
amygdala	UBERON:0001876	85.66	gold quality
pituitary gland	UBERON:0000007	83.99	gold quality
cingulate cortex	UBERON:0003027	83.68	gold quality
anterior cingulate cortex	UBERON:0009835	83.52	gold quality
adenohypophysis	UBERON:0002196	83.43	gold quality
ganglionic eminence	UBERON:0004023	83.15	gold quality
Ammon’s horn	UBERON:0001954	83.10	gold quality
medial globus pallidus	UBERON:0002477	81.29	gold quality
substantia nigra	UBERON:0002038	81.25	gold quality
forebrain	UBERON:0001890	80.33	gold quality
islet of Langerhans	UBERON:0000006	80.18	gold quality
cortical plate	UBERON:0005343	79.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.81	gold quality
telencephalon	UBERON:0001893	79.78	gold quality
midbrain	UBERON:0001891	79.39	gold quality
temporal lobe	UBERON:0001871	79.38	gold quality
right frontal lobe	UBERON:0002810	78.95	gold quality
brain	UBERON:0000955	78.65	gold quality
central nervous system	UBERON:0001017	78.64	gold quality
parotid gland	UBERON:0001831	78.56	gold quality
spinal cord	UBERON:0002240	78.43	gold quality
globus pallidus	UBERON:0001875	77.20	gold quality
cerebral cortex	UBERON:0000956	77.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	833.97
E-HCAD-10	yes	781.19
E-GEOD-124472	yes	645.10
E-MTAB-6108	yes	347.13
E-ANND-3	no	1.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting LYPD1, 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-5193	100.00	67.26	1744
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-3678-3P	99.31	67.10	1432

Literature-anchored findings (GeneRIF, showing 2)

• The PHTS is involved in HeLaHF reversion independently of the p53 pathway, and Expression profiling revealed that PHTS is one of the genes that is up-regulated in HeLaHF but not in HeLa. (PMID:16413018)
• ALKBH5 suppresses malignancy of hepatocellular carcinoma via m(6)A-guided epigenetic inhibition of LYPD1. (PMID:32772918)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lypd1	ENSMUSG00000026344
rattus_norvegicus	Lypd1	ENSRNOG00000003453

Paralogs (3): CD59 (ENSG00000085063), SLURP1 (ENSG00000126233), LYPD2 (ENSG00000197353)

Protein

Protein identifiers

Ly6/PLAUR domain-containing protein 1 — Q8N2G4 (reviewed: Q8N2G4)

Alternative names: Putative HeLa tumor suppressor

All UniProt accessions (2): Q8N2G4, F8WD77

UniProt curated annotations — full annotation on UniProt →

Function. Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro increases receptor desensitization and decreases affinity for ACh of alpha-4:beta-2-containing nAChRs. May play a role in the intracellular trafficking of alpha-4:beta-2 and alpha-7-containing nAChRs and may inhibit their expression at the cell surface. May be involved in the control of anxiety.

Subunit / interactions. Interacts with CHRNA4 and nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits.

Subcellular location. Cell membrane.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N2G4-1	1	yes
Q8N2G4-2	2
Q8N2G4-3	3
Q8N2G4-4	4

RefSeq proteins (4): NP_001070895, NP_001308163, NP_001308164, NP_653187* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00021

UniProt features (23 total): disulfide bond 6, strand 5, splice variant 3, sequence conflict 2, signal peptide 1, chain 1, propeptide 1, helix 1, domain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ZSS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2G4-F1	75.75	0.33

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): 117

Disulfide bonds (6): 88–97, 101–106, 25–54, 28–37, 46–71, 77–100

Glycosylation sites (1): 45

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): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_BEHAVIOR, LI_WILMS_TUMOR, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_CELL_CELL_SIGNALING, CEBP_Q2

GO Biological Process (6): behavioral fear response (GO:0001662), synaptic transmission, cholinergic (GO:0007271), response to nicotine (GO:0035094), protein localization to plasma membrane (GO:0072659), acetylcholine receptor signaling pathway (GO:0095500), negative regulation of protein localization to plasma membrane (GO:1903077)

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

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
behavioral defense response	1
fear response	1
chemical synaptic transmission	1
response to chemical	1
protein localization to membrane	1
protein localization to cell periphery	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	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

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPD1	GPR39	O43194	890
LYPD1	SLURP1	P55000	795
LYPD1	PLAUR	Q03405	678
LYPD1	CD59	P13987	650
LYPD1	LYNX1	P0DP58	633
LYPD1	ALKBH5	Q6P6C2	434
LYPD1	ZNF723	P0DPD5	431
LYPD1	LYPD6	Q86Y78	379
LYPD1	DAPL1	A0PJW8	360
LYPD1	SHISAL1	Q3SXP7	360
LYPD1	NXPH1	P58417	347
LYPD1	LYPD6B	Q8NI32	347
LYPD1	CCDC102B	Q68D86	346
LYPD1	LYPD5	Q6UWN5	342
LYPD1	CALB1	P05937	334

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SPINK7	UBB	psi-mi:“MI:0914”(association)	0.530
LYPD1	HLA-C	psi-mi:“MI:0914”(association)	0.350
LYPD1	LRP5	psi-mi:“MI:0914”(association)	0.350
LYPD1	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): LYPD1 (Affinity Capture-MS), SPSB3 (Affinity Capture-MS), VWDE (Affinity Capture-MS), PCSK5 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), EOGT (Affinity Capture-MS), WNT5A (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), RAB6B (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), PTPRK (Affinity Capture-MS)

ESM2 similar proteins: A2VE33, A8HDK4, A8S6B0, C0STK8, C0STK9, I6PG79, O12962, O55006, O55162, O57690, O95274, P0DQP7, P0DQX3, P0DUK5, P0DUK6, P35459, P35460, P58019, P60591, P60592, P81827, P81828, P82143, P82144, P83121, Q05588, Q3UN54, Q66H42, Q6MG58, Q6UWN5, Q6UX82, Q78CF9, Q7LZI1, Q7LZI2, Q7TQN2, Q8BLC3, Q8N2G4, Q8VEN2, Q90358, Q91YK8

Diamond homologs: Q66H42, Q8BLC3, Q8N2G4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

959 predictions. Top by Δscore:

Variant	Effect	Δscore
2:132645084:T:TA	acceptor_gain	1.0000
2:132646127:C:A	donor_gain	1.0000
2:132668394:TCTTA:T	donor_loss	1.0000
2:132668395:CTTA:C	donor_loss	1.0000
2:132668396:TTACC:T	donor_loss	1.0000
2:132668397:TACCG:T	donor_loss	1.0000
2:132668398:A:AC	donor_gain	1.0000
2:132668398:A:T	donor_loss	1.0000
2:132668398:ACCGG:A	donor_gain	1.0000
2:132668399:C:CA	donor_gain	1.0000
2:132668399:CCG:C	donor_gain	1.0000
2:132668399:CCGG:C	donor_gain	1.0000
2:132668399:CCGGC:C	donor_gain	1.0000
2:132668535:AGCC:A	acceptor_loss	1.0000
2:132668538:C:CC	acceptor_gain	1.0000
2:132668538:CT:C	acceptor_loss	1.0000
2:132668539:T:G	acceptor_loss	1.0000
2:132645071:T:TA	acceptor_gain	0.9900
2:132645084:T:A	acceptor_loss	0.9900
2:132645088:C:CA	acceptor_gain	0.9900
2:132645090:T:TA	acceptor_gain	0.9900
2:132645094:T:TA	acceptor_gain	0.9900
2:132645099:A:AC	acceptor_loss	0.9900
2:132645099:A:AG	acceptor_gain	0.9900
2:132645099:AG:A	acceptor_gain	0.9900
2:132645099:AGG:A	acceptor_gain	0.9900
2:132645100:G:GG	acceptor_gain	0.9900
2:132645100:GG:G	acceptor_gain	0.9900
2:132645100:GGG:G	acceptor_gain	0.9900
2:132645100:GGGC:G	acceptor_gain	0.9900

AlphaMissense

919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:132646264:C:A	K69N	0.999
2:132646264:C:G	K69N	0.999
2:132646268:C:G	R68P	0.999
2:132668429:C:G	C54S	0.999
2:132668430:A:G	C54R	0.999
2:132668430:A:T	C54S	0.999
2:132668452:G:C	C46W	0.999
2:132668453:C:G	C46S	0.999
2:132668453:C:T	C46Y	0.999
2:132668454:A:G	C46R	0.999
2:132668454:A:T	C46S	0.999
2:132646154:C:G	C106S	0.998
2:132646155:A:T	C106S	0.998
2:132646211:A:C	F87C	0.998
2:132646240:A:C	C77W	0.998
2:132646242:A:G	C77R	0.998
2:132646258:A:C	C71W	0.998
2:132646259:C:G	C71S	0.998
2:132646259:C:T	C71Y	0.998
2:132646260:A:T	C71S	0.998
2:132668428:A:C	C54W	0.998
2:132668453:C:A	C46F	0.998
2:132668480:C:G	C37S	0.998
2:132668481:A:T	C37S	0.998
2:132668515:G:C	C25W	0.998
2:132668516:C:G	C25S	0.998
2:132668517:A:T	C25S	0.998
2:132646150:G:C	N107K	0.997
2:132646150:G:T	N107K	0.997
2:132646154:C:T	C106Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000219518 (2:132647777 C>T), RS1000230276 (2:132666414 C>T), RS1000241048 (2:132671419 A>ACGCC), RS1000290167 (2:132671609 A>G), RS1000420941 (2:132647601 G>A,C), RS1000487772 (2:132654472 A>G), RS1000502215 (2:132665188 G>A), RS1000559854 (2:132648948 T>C), RS1000573655 (2:132670397 C>A), RS1000809015 (2:132648903 T>G), RS1000881123 (2:132649129 C>G), RS1000893682 (2:132670822 G>T), RS1000963271 (2:132644356 A>T), RS1001127712 (2:132660733 T>TTTG), RS1001160120 (2:132648711 T>C)

Disease associations

OMIM: gene MIM:610450 | 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
GCST009391_1876	Metabolite levels	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010414	triacylglycerol 52:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression, increases expression	6
bisphenol A	affects expression, decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, increases expression, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, affects methylation	3
methylmercuric chloride	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Cisplatin	affects cotreatment, decreases expression, affects expression	2
Doxorubicin	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression, increases expression	2
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
archazolid B	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1

Clinical trials (associated diseases)

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