PGLYRP4

Summary

PGLYRP4 (peptidoglycan recognition protein 4, HGNC:30015) is a protein-coding gene on chromosome 1q21.3, encoding Peptidoglycan recognition protein 4 (Q96LB8). Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria.

Summary: This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. These proteins are part of the innate immune system and recognize peptidoglycan, a ubiquitous component of bacterial cell walls. This antimicrobial protein binds to murein peptidoglycans of Gram-positive bacteria.

Source: NCBI Gene 57115 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_020393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30015
Approved symbol	PGLYRP4
Name	peptidoglycan recognition protein 4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	SBBI67, PGRPIB, PGLYRPIbeta, PGRP-Ibeta
Ensembl gene	ENSG00000163218
Ensembl biotype	protein_coding
OMIM	608198
Entrez	57115

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000359650, ENST00000368739, ENST00000490266

RefSeq mRNA: 1 — MANE Select: NM_020393 NM_020393

CCDS: CCDS30871

Canonical transcript exons

ENST00000359650 — 9 exons

Exon	Start	End
ENSE00001072550	153341627	153341779
ENSE00001202772	153337181	153337299
ENSE00001409622	153345169	153345382
ENSE00001426683	153340381	153340579
ENSE00001512647	153330120	153330945
ENSE00001784702	153343090	153343208
ENSE00001912151	153348528	153348841
ENSE00003459611	153346102	153346191
ENSE00003573397	153347884	153347978

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 85.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1940 / max 47.0627, expressed in 55 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14604	0.1808	55
14603	0.0132	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	85.10	gold quality
olfactory bulb	UBERON:0002264	84.81	gold quality
skin of abdomen	UBERON:0001416	83.81	gold quality
type B pancreatic cell	CL:0000169	82.62	gold quality
skin of leg	UBERON:0001511	82.45	gold quality
zone of skin	UBERON:0000014	81.05	gold quality
diaphragm	UBERON:0001103	80.41	gold quality
cervix squamous epithelium	UBERON:0006922	80.32	gold quality
esophagus mucosa	UBERON:0002469	79.73	gold quality
upper leg skin	UBERON:0004262	77.50	gold quality
cervix epithelium	UBERON:0004801	76.24	silver quality
tibialis anterior	UBERON:0001385	74.93	silver quality
ileal mucosa	UBERON:0000331	71.83	gold quality
pancreatic ductal cell	CL:0002079	71.39	silver quality
vagina	UBERON:0000996	71.21	gold quality
hair follicle	UBERON:0002073	70.94	gold quality
squamous epithelium	UBERON:0006914	70.21	gold quality
tongue squamous epithelium	UBERON:0006919	69.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.80	gold quality
gingival epithelium	UBERON:0001949	68.60	gold quality
amniotic fluid	UBERON:0000173	68.30	gold quality
epithelium of esophagus	UBERON:0001976	67.94	silver quality
penis	UBERON:0000989	67.81	gold quality
mammalian vulva	UBERON:0000997	67.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.47	gold quality
gingiva	UBERON:0001828	67.36	gold quality
palpebral conjunctiva	UBERON:0001812	67.02	silver quality
esophagus squamous epithelium	UBERON:0006920	66.98	gold quality
nasal cavity epithelium	UBERON:0005384	66.71	gold quality
myocardium	UBERON:0002349	66.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PGLYRP4, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4695-5P	99.06	64.87	1151

Literature-anchored findings (GeneRIF, showing 5)

• Results describe the function of mammalian antimicrobial peptidoglycan recognition proteins 3 and 4, and show that they are a new class of bactericidal and bacteriostatic proteins. (PMID:16354652)
• Data are consistent with previous reports of association of psoriasis with genes on 1q21, and suggest a role for Pglyrp4 in skin biology. (PMID:16362825)
• This study demonistrated that PGLYRP4 single-nucleotide polymorphisms is risk of Parkinson’s disease. (PMID:24838182)
• a significant induction of three PGLYRPs 2-4 in primary human corneal epithelial cells (HCECs) exposed to live or heat-killed Candida albicans, is reported. (PMID:26039076)
• Peptidoglycan Recognition Protein 4 Limits Bacterial Clearance and Inflammation in Lungs by Control of the Gut Microbiota. (PMID:31616404)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pglyrp4	ENSMUSG00000042250
rattus_norvegicus	Pglyrp4	ENSRNOG00000021798
drosophila_melanogaster	PGRP-SA	FBGN0030310
drosophila_melanogaster	PGRP-LE	FBGN0030695
drosophila_melanogaster	PGRP-SC1b	FBGN0033327
drosophila_melanogaster	PGRP-SD	FBGN0035806
drosophila_melanogaster	PGRP-LF	FBGN0035977
drosophila_melanogaster	PGRP-SC2	FBGN0043575
drosophila_melanogaster	PGRP-SC1a	FBGN0043576
drosophila_melanogaster	PGRP-SB2	FBGN0043577
drosophila_melanogaster	PGRP-SB1	FBGN0043578
drosophila_melanogaster	PGRP-LD	FBGN0260458

Paralogs (3): PGLYRP1 (ENSG00000008438), PGLYRP3 (ENSG00000159527), PGLYRP2 (ENSG00000161031)

Protein

Protein identifiers

Peptidoglycan recognition protein 4 — Q96LB8 (reviewed: Q96LB8)

Alternative names: Peptidoglycan recognition protein I-beta, Peptidoglycan recognition protein intermediate beta

All UniProt accessions (1): Q96LB8

UniProt curated annotations — full annotation on UniProt →

Function. Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Also binds to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with PGLYRP3; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Detected in skin epidermis, eccrine sweat glands and ducts, mucous cells in the submandibular salivary gland, mucous cells in the throat, ciliary body epithelial cells of the eye, small intestine, colon, stomach and in mature epithelial cells of the tongue (at protein level). High expression in skin and esophagus. Expressed also to a much lesser extent in the tonsils and thymus.

Post-translational modifications. N-glycosylated.

Induction. Up-regulated by exposure to Gram-positive and Gram-negative bacteria.

Similarity. Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LB8-1	1	yes
Q96LB8-2	2

RefSeq proteins (1): NP_065126* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002502	Amidase_domain	Domain
IPR006619	PGRP_domain_met/bac	Domain
IPR015510	PGRP	Family
IPR036505	Amidase/PGRP_sf	Homologous_superfamily

Pfam: PF01510

UniProt features (39 total): strand 9, sequence variant 6, helix 6, glycosylation site 5, disulfide bond 3, domain 2, region of interest 2, binding site 2, signal peptide 1, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2EAX	X-RAY DIFFRACTION	2.1
2EAV	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LB8-F1	81.86	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 263; 274

Disulfide bonds (3): 210–332, 226–270, 246–252

Glycosylation sites (5): 109, 145, 247, 22, 39

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 75 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_DETECTION_OF_OTHER_ORGANISM, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_HUMORAL_IMMUNE_RESPONSE, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_DETECTION_OF_STIMULUS, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, MODULE_48

GO Biological Process (9): immune response (GO:0006955), peptidoglycan catabolic process (GO:0009253), detection of bacterium (GO:0016045), killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), innate immune response (GO:0045087), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), immune system process (GO:0002376)

GO Molecular Function (5): zinc ion binding (GO:0008270), N-acetylmuramoyl-L-alanine amidase activity (GO:0008745), peptidoglycan immune receptor activity (GO:0016019), peptidoglycan binding (GO:0042834), protein heterodimerization activity (GO:0046982)

GO Cellular Component (3): extracellular region (GO:0005576), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to bacterium	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
peptidoglycan metabolic process	1
glycosaminoglycan catabolic process	1
detection of other organism	1
cell killing	1
disruption of cell in another organism	1
defense response	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
antimicrobial humoral response	1
biological_process	1
transition metal ion binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
peptidoglycan muralytic activity	1
pattern recognition receptor activity	1
peptidoglycan binding	1
glycosaminoglycan binding	1
protein dimerization activity	1
cellular_component	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGLYRP4	LCE3B	Q5TA77	800
PGLYRP4	LCE3C	Q5T5A8	723
PGLYRP4	LCE1A	Q5T7P2	719
PGLYRP4	IVL	P07476	561
PGLYRP4	LORICRIN	P23490	499
PGLYRP4	THSD7B	Q9C0I4	453
PGLYRP4	PGLYRP2	Q96PD5	452
PGLYRP4	SNTG2	Q9NY99	438
PGLYRP4	SYT6	Q5T7P8	432
PGLYRP4	ABCA13	Q86UQ4	430
PGLYRP4	HLA-C	P04222	386
PGLYRP4	FREM3	P0C091	377
PGLYRP4	NLGN3	Q9NZ94	377
PGLYRP4	CLDN17	P56750	374
PGLYRP4	SLC35F1	Q5T1Q4	372

IntAct

0 interactions, top by confidence:

BioGRID (2): PGLYRP4 (Negative Genetic), PGLYRP4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A547, A6QPN6, D2GZV9, E1BPW0, O18956, O75356, O75594, O93295, P10852, P15396, P22413, P49961, P55772, P57110, P70665, P82450, P97535, P97687, Q0V8L2, Q0VB07, Q53H76, Q58CQ9, Q5E9H0, Q5R5M5, Q5RBQ5, Q5RFU0, Q67BJ4, Q6P6S9, Q6YGZ1, Q71RP1, Q794F9, Q8K0L2, Q8TE60, Q8VI78, Q95194, Q96LB8, Q96LB9, Q99JP7, Q99MZ4, Q9HAT2

Diamond homologs: A1A547, B5T255, C0HK98, C0HK99, D1L2U8, O75594, O76537, O88593, P00806, P20331, Q0VB07, Q3ZFI3, Q70PR8, Q70PU1, Q70PU2, Q70PW6, Q70PY2, Q765P2, Q765P3, Q765P4, Q866Y3, Q8INK6, Q8SPP7, Q8VCS0, Q96LB8, Q96LB9, Q96PD5, Q9GK12, Q9GNK5, Q9JLN4, Q9V4X2, Q9VS97, Q9VV96, Q9VXN9, Q9VYX7, Q9XTN0, Q8SXQ7, Q95T64, Q9GN97

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1554 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153337309:C:CT	acceptor_gain	1.0000
1:153340379:A:AC	donor_gain	1.0000
1:153340380:C:CC	donor_gain	1.0000
1:153341625:AC:A	donor_gain	1.0000
1:153341626:CC:C	donor_gain	1.0000
1:153340376:CTCA:C	donor_gain	0.9900
1:153340382:TATA:T	donor_gain	0.9900
1:153340383:ATAA:A	donor_gain	0.9900
1:153340558:C:CT	acceptor_gain	0.9900
1:153341626:CCCTT:C	donor_gain	0.9900
1:153345189:A:AC	donor_gain	0.9900
1:153345190:C:CC	donor_gain	0.9900
1:153345273:A:C	acceptor_gain	0.9900
1:153346096:GTTTA:G	donor_loss	0.9900
1:153346098:TTA:T	donor_loss	0.9900
1:153346099:TACCT:T	donor_loss	0.9900
1:153346101:CCTT:C	donor_loss	0.9900
1:153346188:TCAC:T	acceptor_gain	0.9900
1:153346189:CACC:C	acceptor_gain	0.9900
1:153346189:CACCT:C	acceptor_loss	0.9900
1:153346191:CCT:C	acceptor_loss	0.9900
1:153346192:C:CG	acceptor_loss	0.9900
1:153346193:T:C	acceptor_loss	0.9900
1:153337176:CTTA:C	donor_loss	0.9800
1:153337177:TTA:T	donor_loss	0.9800
1:153337178:TAC:T	donor_loss	0.9800
1:153340383:ATAAC:A	donor_gain	0.9800
1:153340580:C:CC	acceptor_gain	0.9800
1:153343209:C:CC	acceptor_gain	0.9800
1:153345167:A:AC	donor_gain	0.9800

AlphaMissense

2430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153337185:G:C	F313L	0.987
1:153337185:G:T	F313L	0.987
1:153337187:A:G	F313L	0.987
1:153337296:G:C	F276L	0.979
1:153337296:G:T	F276L	0.979
1:153337298:A:G	F276L	0.979
1:153340548:C:A	W219C	0.977
1:153340548:C:G	W219C	0.977
1:153337297:A:G	F276S	0.967
1:153330776:G:C	F371L	0.965
1:153330776:G:T	F371L	0.965
1:153330778:A:G	F371L	0.965
1:153337297:A:C	F276C	0.955
1:153340550:A:G	W219R	0.955
1:153340550:A:T	W219R	0.955
1:153337197:G:C	F309L	0.951
1:153337197:G:T	F309L	0.951
1:153337199:A:G	F309L	0.951
1:153337254:C:A	W290C	0.951
1:153337254:C:G	W290C	0.951
1:153337256:A:G	W290R	0.950
1:153337256:A:T	W290R	0.950
1:153337198:A:G	F309S	0.946
1:153330785:C:A	W368C	0.945
1:153330785:C:G	W368C	0.945
1:153337265:C:A	G287W	0.945
1:153337186:A:C	F313C	0.943
1:153330787:A:G	W368R	0.942
1:153330787:A:T	W368R	0.942
1:153337193:C:A	G311C	0.941

dbSNP variants (sampled 300 via entrez): RS1000143200 (1:153332762 C>A), RS1000242168 (1:153344708 T>A), RS1000293107 (1:153344996 A>G), RS1000492769 (1:153333007 C>T), RS1000583147 (1:153345981 A>C,G), RS1000636818 (1:153346246 T>C), RS1000792759 (1:153334466 A>T), RS1000796207 (1:153349188 C>G,T), RS1000843694 (1:153334730 G>C), RS1000851852 (1:153348902 C>G), RS1001080560 (1:153343917 A>G), RS1001200840 (1:153340855 T>C,G), RS1001297173 (1:153343918 T>C), RS1001309709 (1:153333222 A>G), RS1001469169 (1:153331445 T>C)

Disease associations

OMIM: gene MIM:608198 | 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
GCST008916_87	Asthma	2.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2916205	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2916205	PGLYRP4	3	2.00	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroquinone	increases expression	1
arsenic disulfide	increases methylation	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Allergens	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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