LYPD4

Summary

LYPD4 (LY6/PLAUR domain containing 4, HGNC:28659) is a protein-coding gene on chromosome 19q13.2, encoding Ly6/PLAUR domain-containing protein 4 (Q6UWN0).

Predicted to be located in extracellular region and plasma membrane. Predicted to be active in plasma membrane raft.

Source: NCBI Gene 147719 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_173506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28659
Approved symbol	LYPD4
Name	LY6/PLAUR domain containing 4
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC42718
Ensembl gene	ENSG00000273111
Ensembl biotype	protein_coding
Entrez	147719

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000343055, ENST00000601246, ENST00000609812

RefSeq mRNA: 2 — MANE Select: NM_173506 NM_001291419, NM_173506

CCDS: CCDS12587, CCDS77303

Canonical transcript exons

ENST00000609812 — 5 exons

Exon	Start	End
ENSE00003703850	41838881	41839024
ENSE00003709434	41839219	41839405
ENSE00003710564	41843578	41844683
ENSE00003725956	41837074	41837345
ENSE00003726897	41837935	41838261

Expression profiles

Bgee: expression breadth broad, 34 present calls, max score 99.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6506 / max 638.7363, expressed in 9 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181095	0.4706	4
181090	0.0815	6
181096	0.0431	3
181093	0.0159	3
208835	0.0157	3
181094	0.0123	3
181097	0.0066	3
181091	0.0027	1
181092	0.0023	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.46	gold quality
left testis	UBERON:0004533	97.17	gold quality
right testis	UBERON:0004534	97.06	gold quality
testis	UBERON:0000473	93.81	gold quality
adult organism	UBERON:0007023	91.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.86	gold quality
tibialis anterior	UBERON:0001385	75.47	silver quality
oocyte	CL:0000023	75.27	gold quality
secondary oocyte	CL:0000655	75.18	gold quality
kidney epithelium	UBERON:0004819	73.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.24	gold quality
cardiac muscle of right atrium	UBERON:0003379	70.20	gold quality
left ventricle myocardium	UBERON:0006566	69.97	gold quality
ileal mucosa	UBERON:0000331	69.39	silver quality
upper arm skin	UBERON:0004263	66.92	gold quality
deltoid	UBERON:0001476	61.06	gold quality
myocardium	UBERON:0002349	58.68	gold quality
pancreatic ductal cell	CL:0002079	58.20	silver quality
superficial temporal artery	UBERON:0001614	55.66	gold quality
nasal cavity epithelium	UBERON:0005384	55.29	gold quality
tendon of biceps brachii	UBERON:0008188	55.09	gold quality
epithelial cell of pancreas	CL:0000083	54.43	gold quality
quadriceps femoris	UBERON:0001377	53.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	51.15	gold quality
vastus lateralis	UBERON:0001379	51.07	gold quality
body of tongue	UBERON:0011876	48.17	gold quality
muscle tissue	UBERON:0002385	47.41	gold quality
blood	UBERON:0000178	46.77	gold quality
skeletal muscle tissue	UBERON:0001134	46.49	gold quality
cauda epididymis	UBERON:0004360	44.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lypd4	ENSMUSG00000062732
rattus_norvegicus	Lypd4	ENSRNOG00000020098

Paralogs (2): TEX101 (ENSG00000131126), CD177 (ENSG00000204936)

Protein

Protein identifiers

Ly6/PLAUR domain-containing protein 4 — Q6UWN0 (reviewed: Q6UWN0)

All UniProt accessions (2): A8K8E0, Q6UWN0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWN0-1	1	yes
Q6UWN0-2	2

RefSeq proteins (2): NP_001278348, NP_775777* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR051899	Fert-Immune_med_protein	Family

Pfam: PF00021

UniProt features (9 total): signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1, glycosylation site 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWN0-F1	84.87	0.62

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): 225

Glycosylation sites (1): 117

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: 41 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_SPERM_EGG_RECOGNITION, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOBP_BINDING_OF_SPERM_TO_ZONA_PELLUCIDA, GOCC_SECRETORY_VESICLE, GOCC_SIDE_OF_MEMBRANE, GOCC_ACROSOMAL_VESICLE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_PLASMA_MEMBRANE_RAFT, MIKKELSEN_IPS_HCP_WITH_H3_UNMETHYLATED, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MIKKELSEN_ES_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3

GO Biological Process (3): binding of sperm to zona pellucida (GO:0007339), sperm migration through the uterotubal junction (GO:0160131), single fertilization (GO:0007338)

GO Molecular Function (0):

GO Cellular Component (6): acrosomal vesicle (GO:0001669), extracellular region (GO:0005576), plasma membrane (GO:0005886), plasma membrane raft (GO:0044853), 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
sperm-egg recognition	1
cell migration	1
multicellular organismal reproductive process	1
fertilization	1
secretory granule	1
cell periphery	1
plasma membrane	1
membrane raft	1
plasma membrane region	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYPD4	LY6H	O94772	645
LYPD4	LY6L	H3BQJ8	630
LYPD4	PATE3	B3GLJ2	625
LYPD4	LY6K	Q17RY6	592
LYPD4	PATE4	P0C8F1	589
LYPD4	LYPD2	Q6UXB3	586
LYPD4	PINLYP	A6NC86	586
LYPD4	SPACA4	Q8TDM5	585
LYPD4	PATE2	Q6UY27	585
LYPD4	SLURP1	P55000	582
LYPD4	DMRTC2	Q8IXT2	571
LYPD4	PATE1	Q8WXA2	558
LYPD4	C10orf120	Q5SQS8	557
LYPD4	LYPD5	Q6UWN5	541
LYPD4	C5orf47	Q569G3	531

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LYPD4	KRAS	psi-mi:“MI:0915”(physical association)	0.370
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
LYPD4	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (171): CBWD3 (Affinity Capture-MS), NPTX2 (Affinity Capture-MS), OBSCN (Affinity Capture-MS), FBXL18 (Affinity Capture-MS), FAM198A (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), ERN1 (Affinity Capture-MS), GDF11 (Affinity Capture-MS), FUT11 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), NBR1 (Affinity Capture-MS), LSS (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), GREB1L (Affinity Capture-MS)

ESM2 similar proteins: B3MFC2, B3NSF6, B4QBL6, B5A5T4, B5E022, D3ZTT2, D4A6L0, H3BQJ8, O43653, P12645, P19438, P22444, P23352, P46657, P49002, P50555, P57096, P58658, P58659, Q16553, Q1RMB5, Q28216, Q32LD3, Q505J3, Q568T5, Q5R510, Q5T848, Q66IA6, Q68US5, Q6UWL2, Q6UWN0, Q6UX15, Q6WN34, Q80XH4, Q86Y78, Q8BHE5, Q8BPP5, Q8BVP6, Q8C351, Q8C419

Diamond homologs: Q32LD3, Q6UWN0, Q8BVP6, Q8N6Q3, Q8R2S8, Q7TQN2, Q924B5, Q9BY14, Q9JMI7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

670 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41837344:CC:C	acceptor_gain	0.9900
19:41837345:CC:C	acceptor_gain	0.9900
19:41838018:T:TA	donor_gain	0.9900
19:41838077:A:AC	donor_gain	0.9900
19:41838078:G:C	donor_gain	0.9900
19:41844599:G:C	donor_gain	0.9900
19:41838032:G:A	donor_gain	0.9800
19:41837345:CCT:C	acceptor_loss	0.9700
19:41837346:C:CC	acceptor_gain	0.9700
19:41837346:CTGTA:C	acceptor_loss	0.9700
19:41837347:T:G	acceptor_loss	0.9700
19:41837348:G:C	acceptor_loss	0.9700
19:41838022:T:TA	donor_gain	0.9700
19:41838087:G:A	donor_gain	0.9700
19:41844575:A:C	donor_gain	0.9700
19:41844586:AGG:A	donor_gain	0.9700
19:41844542:G:C	donor_gain	0.9600
19:41838870:G:C	donor_gain	0.9500
19:41844505:A:C	donor_gain	0.9500
19:41844598:A:AC	donor_gain	0.9500
19:41838260:CC:C	acceptor_gain	0.9400
19:41838261:CC:C	acceptor_gain	0.9400
19:41838869:A:AC	donor_gain	0.9400
19:41844428:A:AT	donor_gain	0.9400
19:41844496:A:AT	donor_gain	0.9400
19:41844509:CAGCG:C	donor_gain	0.9400
19:41838259:TCCC:T	acceptor_loss	0.9300
19:41838261:CCTGA:C	acceptor_loss	0.9300
19:41838263:T:A	acceptor_loss	0.9300
19:41844547:G:C	donor_gain	0.9300

AlphaMissense

1597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41838233:T:A	K80N	0.995
19:41838233:T:G	K80N	0.995
19:41838951:C:A	W47C	0.994
19:41838951:C:G	W47C	0.994
19:41838125:G:C	N116K	0.993
19:41838125:G:T	N116K	0.993
19:41838234:T:A	K80I	0.991
19:41838910:C:G	C61S	0.990
19:41838911:A:T	C61S	0.990
19:41838953:A:G	W47R	0.990
19:41838953:A:T	W47R	0.990
19:41838126:T:A	N116I	0.989
19:41838129:C:G	C115S	0.988
19:41838130:A:T	C115S	0.988
19:41839006:C:G	C29S	0.988
19:41839007:A:T	C29S	0.988
19:41838928:C:G	C55S	0.987
19:41838929:A:T	C55S	0.987
19:41838957:C:A	W45C	0.986
19:41838957:C:G	W45C	0.986
19:41838160:A:G	S105P	0.985
19:41838228:C:G	C82S	0.985
19:41838229:A:T	C82S	0.985
19:41838236:A:C	F79L	0.983
19:41838236:A:T	F79L	0.983
19:41838238:A:G	F79L	0.983
19:41838928:C:T	C55Y	0.982
19:41838910:C:T	C61Y	0.981
19:41838163:C:G	A104P	0.980
19:41839005:G:C	C29W	0.980

dbSNP variants (sampled 300 via entrez): RS1000084791 (19:41838926 T>G), RS1000371697 (19:41835132 T>C), RS1000381957 (19:41841204 G>A,T), RS1000560049 (19:41845743 C>G), RS1000579438 (19:41839738 A>G), RS1000684021 (19:41840292 T>A), RS1001117677 (19:41840062 A>G,T), RS1001270419 (19:41842274 C>T), RS1001372761 (19:41836702 A>C,G), RS1001804918 (19:41842563 A>C), RS1003178880 (19:41838476 C>T), RS1003742123 (19:41844359 C>T), RS1004332060 (19:41844100 A>T), RS1004380739 (19:41844317 G>A,T), RS1004665891 (19:41842254 C>T)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases methylation	1

Clinical trials (associated diseases)

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