LYPD6B

Summary

LYPD6B (LY6/PLAUR domain containing 6B, HGNC:27018) is a protein-coding gene on chromosome 2q23.2, encoding Ly6/PLAUR domain-containing protein 6B (Q8NI32). Likely acts as a modulator of nicotinic acetylcholine receptors (nAChRs) activity.

Enables acetylcholine receptor regulator activity. Predicted to be located in extracellular region and plasma membrane.

Source: NCBI Gene 130576 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_177964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27018
Approved symbol	LYPD6B
Name	LY6/PLAUR domain containing 6B
Location	2q23.2
Locus type	gene with protein product
Status	Approved
Aliases	CT116, LYPD7
Ensembl gene	ENSG00000150556
Ensembl biotype	protein_coding
Entrez	130576

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000280115, ENST00000409029, ENST00000409642, ENST00000409876, ENST00000437627, ENST00000442722, ENST00000450639, ENST00000473800, ENST00000473975, ENST00000480545, ENST00000498249, ENST00000899443, ENST00000899444, ENST00000899445, ENST00000899446, ENST00000899447, ENST00000899448, ENST00000899449, ENST00000899450, ENST00000899451, ENST00000899452, ENST00000899453, ENST00000899454, ENST00000924612, ENST00000951161, ENST00000951162

RefSeq mRNA: 6 — MANE Select: NM_177964 NM_001317002, NM_001317003, NM_001317004, NM_001317005, NM_001317006, NM_177964

CCDS: CCDS46423, CCDS82519

Canonical transcript exons

ENST00000409642 — 7 exons

Exon	Start	End
ENSE00001585661	149038699	149038801
ENSE00003556354	149208314	149208412
ENSE00003588934	149130883	149130953
ENSE00003592408	149205253	149205404
ENSE00003596936	149212992	149213122
ENSE00003678634	149214546	149215262
ENSE00003686458	149160764	149160835

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 96.97.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0558 / max 76.2753, expressed in 696 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23012	1.1042	426
23014	0.6337	280
23010	0.3548	205
23011	0.2766	153
23008	0.2113	95
23015	0.1563	98
23009	0.1480	61
23013	0.1449	84
23016	0.0261	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	96.97	gold quality
right uterine tube	UBERON:0001302	96.17	gold quality
skin of leg	UBERON:0001511	95.84	gold quality
zone of skin	UBERON:0000014	94.65	gold quality
gall bladder	UBERON:0002110	93.55	gold quality
nasal cavity epithelium	UBERON:0005384	93.18	silver quality
right testis	UBERON:0004534	92.36	gold quality
left testis	UBERON:0004533	92.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.38	gold quality
testis	UBERON:0000473	88.96	gold quality
palpebral conjunctiva	UBERON:0001812	86.17	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.79	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.30	gold quality
pancreatic ductal cell	CL:0002079	85.20	silver quality
upper leg skin	UBERON:0004262	85.10	gold quality
body of stomach	UBERON:0001161	84.70	gold quality
oviduct epithelium	UBERON:0004804	84.66	gold quality
sperm	CL:0000019	84.20	silver quality
bronchial epithelial cell	CL:0002328	83.77	gold quality
epithelium of nasopharynx	UBERON:0001951	83.37	silver quality
epithelial cell of pancreas	CL:0000083	82.84	gold quality
stomach	UBERON:0000945	82.80	gold quality
bronchus	UBERON:0002185	82.70	gold quality
fallopian tube	UBERON:0003889	82.15	gold quality
body of pancreas	UBERON:0001150	81.54	gold quality
nasal cavity mucosa	UBERON:0001826	81.46	gold quality
metanephros cortex	UBERON:0010533	80.89	gold quality
pancreas	UBERON:0001264	79.46	gold quality
seminal vesicle	UBERON:0000998	78.95	gold quality
lower esophagus mucosa	UBERON:0035834	78.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	22.91
E-ANND-3	yes	7.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting LYPD6B, 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-568	99.98	69.86	2084
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-610	96.84	67.98	905
HSA-MIR-6866-5P	96.64	68.06	624
HSA-MIR-6734-5P	95.70	65.56	950

Literature-anchored findings (GeneRIF, showing 2)

• LYPD7 was especially highly expressed in testis, lung, stomach, and prostate. (PMID:18360792)
• Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors. (PMID:33019770)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lypd6b	ENSDARG00000077643
mus_musculus	Lypd6b	ENSMUSG00000026765
rattus_norvegicus	Lypd6b	ENSRNOG00000004614

Paralogs (1): LYPD6 (ENSG00000187123)

Protein

Protein identifiers

Ly6/PLAUR domain-containing protein 6B — Q8NI32 (reviewed: Q8NI32)

All UniProt accessions (5): Q8NI32, F8WB42, F8WCH4, F8WEI1, H7BXI7

UniProt curated annotations — full annotation on UniProt →

Function. Likely acts as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro acts on nAChRs in a subtype- and stoichiometry-dependent manner. Modulates specifically alpha-3(3):beta-4(2) nAChRs by enhancing the sensitivity to ACh, decreasing ACh-induced maximal current response and increasing the rate of desensitization to ACh; has no effect on alpha-7 homomeric nAChRs; modulates alpha-3(2):alpha-5:beta-4(2) nAChRs in the context of CHRNA5/alpha-5 variant Asn-398 but not its wild-type sequence. However, according to another report in vitro it can weakly inhibits alpha-7 nAChRs.

Subcellular location. Cell membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NI32-1	1	yes
Q8NI32-2	2

RefSeq proteins (6): NP_001303931, NP_001303932, NP_001303933, NP_001303934, NP_001303935, NP_808879* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039457	LYPD6-like	Family
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF16975

UniProt features (19 total): disulfide bond 6, strand 4, signal peptide 1, chain 1, splice variant 1, helix 1, turn 1, propeptide 1, domain 1, region of interest 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ZSO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI32-F1	79.96	0.49

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): 164

Disulfide bonds (6): 120–131, 135–140, 62–90, 65–74, 83–109, 115–134

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: 116 (showing top): ROZANOV_MMP14_TARGETS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, ZHAN_MULTIPLE_MYELOMA_LB_UP, CERVERA_SDHB_TARGETS_1_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, CUI_TCF21_TARGETS_2_UP, GAVIN_FOXP3_TARGETS_CLUSTER_P4, GOCC_SIDE_OF_MEMBRANE, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_DN, GOMF_NEUROTRANSMITTER_RECEPTOR_REGULATOR_ACTIVITY, REACTOME_POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS

GO Biological Process (0):

GO Molecular Function (1): acetylcholine receptor regulator activity (GO:0030548)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), 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
membrane	2
acetylcholine receptor activity	1
neurotransmitter receptor regulator activity	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1187 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPD6B	BEND7	Q8N7W2	615
LYPD6B	LY6H	O94772	614
LYPD6B	LYNX1	P0DP58	601
LYPD6B	TATDN3	Q17R31	570
LYPD6B	KIF5C	O60282	543
LYPD6B	MBD5	Q9P267	541
LYPD6B	LRP6	O75581	537
LYPD6B	EPC2	Q52LR7	511
LYPD6B	MMADHC	Q9H3L0	507
LYPD6B	OTOL1	A6NHN0	505
LYPD6B	ANGEL2	Q5VTE6	498
LYPD6B	QTMAN	Q4AE62	475
LYPD6B	LRRC71	Q8N4P6	469
LYPD6B	RPS6KC1	Q96S38	459
LYPD6B	ANHX	E9PGG2	453
LYPD6B	ORC4	O43929	453

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LYPD6B	CST4	psi-mi:“MI:0914”(association)	0.350
LYPD6B	ZNF195	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): LYPD6B (Synthetic Lethality), VMA21 (Two-hybrid), UBR4 (Affinity Capture-MS), CST4 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), IDE (Affinity Capture-MS), TUBB7P (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), FAM115A (Affinity Capture-MS), UGGT2 (Affinity Capture-MS), VWDE (Affinity Capture-MS)

ESM2 similar proteins: A0JNL5, H2LID1, O55006, O55186, O62680, O77541, O95867, O95868, P05533, P0DP57, P0DP59, P0DP61, P0DPQ9, P13987, P27274, P35459, P35460, P35461, P46657, P51447, P55000, P58019, P81827, P81828, P83121, Q14210, Q17RY6, Q28216, Q28785, Q32PB3, Q5R510, Q63317, Q66H42, Q6MG58, Q6UWN5, Q6UXB3, Q7TQN2, Q80ZQ0, Q8BLC3, Q8N2G4

Diamond homologs: D3ZTT2, Q66IA6, Q86Y78, Q8BPP5, Q8NI32, Q9D7F2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2967 predictions. Top by Δscore:

Variant	Effect	Δscore
2:149200620:T:TA	acceptor_gain	1.0000
2:149212975:T:TA	acceptor_gain	1.0000
2:149212985:T:TA	acceptor_gain	1.0000
2:149212989:TA:T	acceptor_loss	1.0000
2:149212990:A:AG	acceptor_gain	1.0000
2:149212990:AGAT:A	acceptor_loss	1.0000
2:149212991:G:C	acceptor_loss	1.0000
2:149212991:G:GC	acceptor_gain	1.0000
2:149213119:TACGG:T	donor_loss	1.0000
2:149213123:G:C	donor_loss	1.0000
2:149213123:G:GG	donor_gain	1.0000
2:149213124:T:TC	donor_loss	1.0000
2:149057730:GTGCT:G	donor_gain	0.9900
2:149131342:A:G	donor_gain	0.9900
2:149149331:T:G	donor_gain	0.9900
2:149149346:ATTTT:A	donor_gain	0.9900
2:149187517:G:GG	donor_gain	0.9900
2:149187580:G:GG	donor_gain	0.9900
2:149200621:G:A	acceptor_gain	0.9900
2:149205401:GACC:G	donor_gain	0.9900
2:149205403:CC:C	donor_gain	0.9900
2:149205405:G:GG	donor_gain	0.9900
2:149208312:A:AG	acceptor_gain	0.9900
2:149208313:G:GG	acceptor_gain	0.9900
2:149208413:G:GG	donor_gain	0.9900
2:149212991:GA:G	acceptor_gain	0.9900
2:149212991:GAT:G	acceptor_gain	0.9900
2:149212991:GATA:G	acceptor_gain	0.9900
2:149212991:GATAC:G	acceptor_gain	0.9900
2:149119097:A:AG	acceptor_gain	0.9800

AlphaMissense

1382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:149208344:T:G	F63C	0.999
2:149213055:A:T	K107I	0.999
2:149213056:A:C	K107N	0.999
2:149213056:A:T	K107N	0.999
2:149208339:G:C	K61N	0.998
2:149208339:G:T	K61N	0.998
2:149208343:T:C	F63L	0.998
2:149208345:T:A	F63L	0.998
2:149208345:T:G	F63L	0.998
2:149208376:T:A	C74S	0.998
2:149208377:G:C	C74S	0.998
2:149208387:G:C	W77C	0.998
2:149208387:G:T	W77C	0.998
2:149208402:G:C	W82C	0.998
2:149208402:G:T	W82C	0.998
2:149208340:T:A	C62S	0.997
2:149208341:G:C	C62S	0.997
2:149213060:T:A	C109S	0.997
2:149213061:G:C	C109S	0.997
2:149208340:T:C	C62R	0.996
2:149208344:T:C	F63S	0.996
2:149208377:G:A	C74Y	0.996
2:149208377:G:T	C74F	0.996
2:149208378:C:G	C74W	0.996
2:149208381:T:A	N75K	0.996
2:149208381:T:G	N75K	0.996
2:149208403:T:A	C83S	0.996
2:149208404:G:C	C83S	0.996
2:149213003:T:A	C90S	0.996
2:149213004:G:C	C90S	0.996

dbSNP variants (sampled 300 via entrez): RS1000000215 (2:149118843 T>C), RS1000004078 (2:149160470 G>T), RS1000018741 (2:149062153 A>G), RS1000030037 (2:149062327 T>C), RS1000048572 (2:149118352 A>T), RS1000062052 (2:149081901 A>G), RS1000074463 (2:149067901 G>A,C,T), RS1000103485 (2:149112124 G>A), RS1000110085 (2:149148615 T>C), RS1000127891 (2:149049356 TGCAC>T), RS1000147757 (2:149067560 TTTG>T), RS1000148778 (2:149206516 C>T), RS1000151330 (2:149203804 G>A), RS1000166066 (2:149043116 G>A), RS1000170371 (2:149071136 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001877_62	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	8.000000e-06
GCST006817_3	Response to antidepressants in depression	5.000000e-06
GCST008154_66	Trunk fat mass	5.000000e-06
GCST010698_6	Subcortical volume (min-P)	5.000000e-08
GCST010699_94	Brain morphology (min-P)	2.000000e-12
GCST010700_37	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_85	Cortical surface area (MOSTest)	8.000000e-09
GCST010702_69	Subcortical volume (MOSTest)	2.000000e-11
GCST010703_181	Brain morphology (MOSTest)	5.000000e-11
GCST011616_25	Cortical volume	3.000000e-12
GCST011617_12	Cortical surface area	2.000000e-16
GCST011617_16	Cortical surface area	2.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	4
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	3
trichostatin A	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation, decreases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	decreases expression, increases expression	2
bisphenol A	increases methylation, affects cotreatment	1
sodium arsenate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
diallyl trisulfide	decreases expression	1
avobenzone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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