LYPD8

Summary

LYPD8 (LY6/PLAUR domain containing 8, HGNC:44208) is a protein-coding gene on chromosome 1q44, encoding Ly6/PLAUR domain-containing protein 8 (Q6UX82). Secreted protein specifically required to prevent invasion of Gram-negative bacteria in the inner mucus layer of the colon epithelium, a portion of the large intestine which is free of commensal microbiota.

Predicted to be involved in defense response to Gram-negative bacterium. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space.

Source: NCBI Gene 646627 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001085474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44208
Approved symbol	LYPD8
Name	LY6/PLAUR domain containing 8
Location	1q44
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000259823
Ensembl biotype	protein_coding
OMIM	617067
Entrez	646627

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000590317, ENST00000877208, ENST00000877209, ENST00000961487, ENST00000961488, ENST00000961489, ENST00000961490

RefSeq mRNA: 2 — MANE Select: NM_001085474 NM_001085474, NM_001291283

CCDS: CCDS73059

Canonical transcript exons

ENST00000590317 — 7 exons

Exon	Start	End
ENSE00002587594	248750524	248750643
ENSE00002619651	248751030	248751130
ENSE00002627550	248748289	248748453
ENSE00002859783	248739415	248739849
ENSE00003733810	248755705	248755759
ENSE00003748294	248755239	248755386
ENSE00003842906	248745142	248745279

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 97.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3471 / max 55.5009, expressed in 55 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
202049	0.2502	46
202053	0.0969	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	97.97	gold quality
colonic mucosa	UBERON:0000317	97.58	gold quality
mucosa of transverse colon	UBERON:0004991	97.50	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.37	gold quality
ileal mucosa	UBERON:0000331	97.14	gold quality
transverse colon	UBERON:0001157	89.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.13	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.14	gold quality
vermiform appendix	UBERON:0001154	77.98	gold quality
large intestine	UBERON:0000059	76.46	gold quality
intestine	UBERON:0000160	75.63	gold quality
colon	UBERON:0001155	75.56	gold quality
small intestine	UBERON:0002108	75.45	gold quality
jejunal mucosa	UBERON:0000399	71.67	gold quality
caecum	UBERON:0001153	71.41	gold quality
prefrontal cortex	UBERON:0000451	64.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.45	gold quality
anterior cingulate cortex	UBERON:0009835	64.11	gold quality
colonic epithelium	UBERON:0000397	63.56	gold quality
right frontal lobe	UBERON:0002810	63.56	gold quality
frontal cortex	UBERON:0001870	61.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.69	gold quality
neocortex	UBERON:0001950	60.98	gold quality
bone marrow cell	CL:0002092	60.81	silver quality
amygdala	UBERON:0001876	59.48	gold quality
cerebral cortex	UBERON:0000956	58.77	gold quality
jejunum	UBERON:0002115	57.57	silver quality
duodenum	UBERON:0002114	57.35	gold quality
caudate nucleus	UBERON:0001873	55.35	gold quality
temporal lobe	UBERON:0001871	54.62	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	1784.67
E-MTAB-8410	yes	13.41
E-ANND-3	yes	7.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting LYPD8, 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-6721-5P	99.93	68.92	2981
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-5090	93.28	60.86	94
HSA-MIR-6775-5P	92.43	61.00	132

Literature-anchored findings (GeneRIF, showing 2)

• Study results revealed that the expression of LYPD8 was significantly reduced in the colorectal cancer (CRC) tissue compared with that in precancerous tissue and normal tissue. The results also revealed increased levels of P65 and STAT3 phosphorylation and increased secretion of IL6 and TNFalpha in CRC tissue compared with levels in precancerous tissue. (PMID:30816524)
• Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease. (PMID:33822948)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-102g19.3	ENSDARG00000086337
danio_rerio	negaly6	ENSDARG00000089123
danio_rerio	ly6m4	ENSDARG00000098616
danio_rerio	ly6m5	ENSDARG00000099332
danio_rerio	ly6m3	ENSDARG00000099416
danio_rerio	si:ch211-134a4.6	ENSDARG00000101786
danio_rerio	ly6m6	ENSDARG00000102159
danio_rerio	ly6m7	ENSDARG00000103060
danio_rerio	ly6m2	ENSDARG00000104775
mus_musculus	Lypd8	ENSMUSG00000013643
rattus_norvegicus	Lypd8	ENSRNOG00000026844

Paralogs (1): PINLYP (ENSG00000234465)

Protein

Protein identifiers

Ly6/PLAUR domain-containing protein 8 — Q6UX82 (reviewed: Q6UX82)

All UniProt accessions (1): Q6UX82

UniProt curated annotations — full annotation on UniProt →

Function. Secreted protein specifically required to prevent invasion of Gram-negative bacteria in the inner mucus layer of the colon epithelium, a portion of the large intestine which is free of commensal microbiota. Prevents invasion of flagellated microbiota by binding to the flagellum of bacteria, such as P.mirabilis, thereby inhibiting bacterial motility in the intestinal lumen. Segregation of intestinal bacteria and epithelial cells in the colon is required to preserve intestinal homeostasis.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Expressed in the large intestine. Preferentially expressed on the epithelial layer exposed to the lumen (at protein level).

Post-translational modifications. Highly N-glycosylated. Not O-glycosylated. GPI-anchored. The GPI-anchor is cleaved, leading to secretion into the colonic lumen.

Similarity. Belongs to the CNF-like-inhibitor family.

RefSeq proteins (2): NP_001078943, NP_001278212 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR050918	CNF-like_PLA2_Inhibitor	Family

UniProt features (14 total): glycosylation site 8, signal peptide 1, chain 1, sequence conflict 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX82-F1	79.82	0.50

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): 215

Glycosylation sites (8): 172, 175, 185, 45, 73, 107, 118, 132

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: 33 (showing top): GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, SABATES_COLORECTAL_ADENOMA_DN, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, chr1q44, GOCC_SIDE_OF_MEMBRANE, GOBP_RESPONSE_TO_BACTERIUM, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, YANG_BCL3_TARGETS_UP, MTOR_UP.V1_UP, WNT_UP.V1_UP, REACTOME_POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS, SFMBT1_TARGET_GENES, MIR6510_5P

GO Biological Process (1): defense response to Gram-negative bacterium (GO:0050829)

GO Molecular Function (0):

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), 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
defense response to bacterium	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPD8	ZG16	O60844	595
LYPD8	REG3G	Q6UW15	507
LYPD8	KRTAP19-6	Q3LI70	493
LYPD8	LY6L	H3BQJ8	480
LYPD8	PINLYP	A6NC86	475
LYPD8	REG3A	Q06141	448
LYPD8	DIRC1	Q969H9	436
LYPD8	PATE3	B3GLJ2	420
LYPD8	LYPD4	Q6UWN0	419
LYPD8	IGFL1	Q6UW32	387
LYPD8	OCEL1	Q9H607	379
LYPD8	TM4SF4	P48230	371
LYPD8	PATE2	Q6UY27	369
LYPD8	ANAPC2	Q9UJX6	364
LYPD8	PLEK2	Q9NYT0	353
LYPD8	PLEK	P08567	353

IntAct

0 interactions, top by confidence:

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: A2VE33, Q6UX82, Q9D7S0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

190 predictions. Top by Δscore:

Variant	Effect	Δscore
1:248739803:A:AC	donor_gain	0.9100
1:248739804:C:CC	donor_gain	0.9100
1:248739723:A:AC	donor_gain	0.8800
1:248739724:C:CC	donor_gain	0.8800
1:248739724:CATTT:C	donor_gain	0.8700
1:248739738:A:C	donor_gain	0.8700
1:248739807:A:AC	donor_gain	0.8500
1:248739808:C:CC	donor_gain	0.8500
1:248739737:A:AC	donor_gain	0.8400
1:248739790:G:T	donor_gain	0.8200
1:248739736:CAA:C	donor_gain	0.8100
1:248739737:AAA:A	donor_gain	0.8100
1:248739726:TTTGC:T	donor_gain	0.7900
1:248739735:TCA:T	donor_gain	0.7900
1:248739739:A:C	donor_gain	0.7900
1:248739743:T:A	donor_gain	0.7900
1:248739733:A:AC	donor_gain	0.7700
1:248739734:C:CC	donor_gain	0.7700
1:248739773:T:TC	donor_gain	0.7600
1:248739732:CA:C	donor_gain	0.7500
1:248739756:C:CA	donor_gain	0.7200
1:248739806:G:T	donor_gain	0.7200
1:248739725:ATTTG:A	donor_gain	0.7100
1:248739740:C:CC	donor_gain	0.7100
1:248739791:A:AC	donor_gain	0.7000
1:248739792:C:CC	donor_gain	0.7000
1:248739734:CTCAA:C	donor_gain	0.6800
1:248739758:T:TA	donor_gain	0.6800
1:248739779:A:T	donor_gain	0.6800
1:248739809:G:C	donor_gain	0.6800

AlphaMissense

1552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:248739816:C:G	C170S	0.979
1:248739817:A:T	C170S	0.979
1:248748342:A:C	F95C	0.977
1:248739814:A:G	S171P	0.976
1:248745189:C:G	C143S	0.976
1:248745190:A:T	C143S	0.976
1:248748420:C:G	C69S	0.975
1:248748421:A:T	C69S	0.975
1:248739820:C:G	G169R	0.974
1:248739747:A:C	F193C	0.973
1:248745243:C:G	C125S	0.972
1:248745244:A:T	C125S	0.972
1:248748421:A:G	C69R	0.972
1:248745244:A:G	C125R	0.971
1:248748372:A:T	V85D	0.971
1:248739817:A:G	C170R	0.970
1:248750553:C:G	C48S	0.970
1:248750554:A:T	C48S	0.970
1:248739820:C:A	G169C	0.968
1:248748378:A:C	F83C	0.968
1:248748419:G:C	C69W	0.968
1:248745190:A:G	C143R	0.967
1:248750578:A:G	C40R	0.967
1:248750554:A:G	C48R	0.966
1:248750577:C:G	C40S	0.966
1:248750578:A:T	C40S	0.966
1:248745188:G:C	C143W	0.965
1:248748420:C:T	C69Y	0.965
1:248745157:C:G	A154P	0.963
1:248739747:A:G	F193S	0.962

dbSNP variants (sampled 300 via entrez): RS1000141378 (1:248749399 G>C), RS1000316916 (1:248755987 G>A), RS1000323397 (1:248741591 G>T), RS1000862557 (1:248746145 T>G), RS1000920816 (1:248754534 C>G), RS1001002655 (1:248740025 G>A), RS1001143342 (1:248746379 C>A,G,T), RS1001290786 (1:248754790 A>T), RS1001517548 (1:248750749 G>A), RS1001586445 (1:248757048 C>G), RS1001678074 (1:248743316 G>A), RS1001820128 (1:248750962 C>A,G), RS1001952401 (1:248757271 C>T), RS1002453953 (1:248739648 G>A,C,T), RS1003059669 (1:248746053 G>T)

Disease associations

OMIM: gene MIM:617067 | 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
GCST002935_1	Lead levels	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Copper	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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