PRELP

Summary

PRELP (proline and arginine rich end leucine rich repeat protein, HGNC:9357) is a protein-coding gene on chromosome 1q32.1, encoding Prolargin (P51888). May anchor basement membranes to the underlying connective tissue.

The protein encoded by this gene is a leucine-rich repeat protein present in connective tissue extracellular matrix. This protein functions as a molecule anchoring basement membranes to the underlying connective tissue. This protein has been shown to bind type I collagen to basement membranes and type II collagen to cartilage. It also binds the basement membrane heparan sulfate proteoglycan perlecan. This protein is suggested to be involved in the pathogenesis of Hutchinson-Gilford progeria (HGP), which is reported to lack the binding of collagen in basement membranes and cartilage. Alternatively spliced transcript variants encoding the same protein have been observed.

Source: NCBI Gene 5549 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_002725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9357
Approved symbol	PRELP
Name	proline and arginine rich end leucine rich repeat protein
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	SLRR2A, prolargin
Ensembl gene	ENSG00000188783
Ensembl biotype	protein_coding
OMIM	601914
Entrez	5549

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000343110, ENST00000864893, ENST00000864894, ENST00000864895, ENST00000942343

RefSeq mRNA: 2 — MANE Select: NM_002725 NM_002725, NM_201348

CCDS: CCDS1438

Canonical transcript exons

ENST00000343110 — 3 exons

Exon	Start	End
ENSE00001375213	203483169	203484157
ENSE00001380814	203475806	203475938
ENSE00001902735	203486706	203491352

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.55.

FANTOM5 (CAGE): breadth broad, TPM avg 49.7247 / max 4538.6233, expressed in 748 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7893	49.3792	747
7894	0.2101	97
201891	0.1354	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.55	gold quality
right coronary artery	UBERON:0001625	99.48	gold quality
synovial joint	UBERON:0002217	99.44	gold quality
popliteal artery	UBERON:0002250	99.33	gold quality
ascending aorta	UBERON:0001496	99.32	gold quality
tibial artery	UBERON:0007610	99.32	gold quality
thoracic aorta	UBERON:0001515	99.31	gold quality
aorta	UBERON:0000947	99.30	gold quality
pericardium	UBERON:0002407	99.29	gold quality
coronary artery	UBERON:0001621	99.07	gold quality
descending thoracic aorta	UBERON:0002345	99.07	gold quality
left coronary artery	UBERON:0001626	99.03	gold quality
tibia	UBERON:0000979	98.99	gold quality
mucosa of stomach	UBERON:0001199	98.94	gold quality
calcaneal tendon	UBERON:0003701	98.82	gold quality
right lung	UBERON:0002167	98.79	gold quality
urethra	UBERON:0000057	98.74	gold quality
right atrium auricular region	UBERON:0006631	97.93	gold quality
endocervix	UBERON:0000458	97.88	gold quality
tibial nerve	UBERON:0001323	97.83	gold quality
vena cava	UBERON:0004087	97.83	gold quality
cardiac atrium	UBERON:0002081	97.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.77	gold quality
lower esophagus	UBERON:0013473	97.72	gold quality
left uterine tube	UBERON:0001303	97.65	gold quality
tendon of biceps brachii	UBERON:0008188	97.61	gold quality
right ovary	UBERON:0002118	97.38	gold quality
left ovary	UBERON:0002119	97.30	gold quality
body of uterus	UBERON:0009853	96.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.84	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	2488.87
E-HCAD-1	yes	74.94
E-GEOD-135922	yes	59.99
E-HCAD-10	yes	29.65
E-MTAB-10287	yes	23.62
E-MTAB-9543	yes	16.24
E-CURD-112	yes	7.26
E-HCAD-35	yes	6.63
E-MTAB-10553	yes	5.97
E-GEOD-84465	yes	5.82
E-HCAD-9	yes	4.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX9

miRNA regulators (miRDB)

159 targeting PRELP, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321

Literature-anchored findings (GeneRIF, showing 16)

• Relative abundance of PRELP mRNA and protein inhuman sclera, and observed age-related variation in scleral PRELP expression suggests that PRELP may play critical role in regulating biomechanical properties of scleral extracellular matrix. (PMID:17093390)
• PRELP overexpression leads to a connective tissue phenotype in the skin, where the organization of collagen fibrils in the dermis was perturbed and the thickness of the hypodermal fat layer was diminished. (PMID:17123807)
• PRELP may down-regulate complement attack at basement membranes and on damaged cartilage and therefore limit pathological complement activation in inflammatory disease such as RA. (PMID:22267731)
• PRELP expression governs stem cells to differentiate into ligament tissue in a mouse model. (PMID:23442027)
• The unique expression of a 38 kDa PRELP in chronic lymphocytic leukemia (CLL) cells may suggest involvement in the pathobiology of CLL (PMID:23826326)
• These findings provide support for a role of the N-terminal region of PRELP as an important regulator of cell adhesion and behaviour, which may be of importance in pathological conditions. (PMID:26920026)
• this study shows that PRELP enhances host innate immunity against Moraxella catarrhalis through increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells (PMID:28148731)
• PRELP was more expressed in peritoneal lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue. (PMID:28678915)
• Up regulation of prolargin in RA suggests the likelihood of an adaptive mechanism to control the increased osteoclastogenesis in RA and may have therapeutic value in controlling the disease. (PMID:29402456)
• A novel biomarker of MMP-cleaved prolargin is elevated in patients with psoriatic arthritis. (PMID:32782251)
• Proteomic identification and validation of novel interactions of the putative tumor suppressor PRELP with membrane proteins including IGFI-R and p75NTR. (PMID:33428936)
• Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer. (PMID:36371227)
• Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma. (PMID:37730606)
• PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin alpha5. (PMID:38992455)
• PRELP inhibits the progression of oral squamous cell carcinoma via inactivation of the NF-kappaB pathway. (PMID:39151326)
• Adipocyte-secreted PRELP promotes adipocyte differentiation and adipose tissue fibrosis by binding with p75[NTR] to activate FAK/MAPK signaling. (PMID:39244119)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prelp	ENSDARG00000070597
mus_musculus	Prelp	ENSMUSG00000041577
rattus_norvegicus	Prelp	ENSRNOG00000003120

Paralogs (10): EPYC (ENSG00000083782), OGN (ENSG00000106809), ECM2 (ENSG00000106823), FMOD (ENSG00000122176), OMG (ENSG00000126861), OMD (ENSG00000127083), LUM (ENSG00000139329), KERA (ENSG00000139330), LINGO4 (ENSG00000213171), LINGO3 (ENSG00000220008)

Protein

Protein identifiers

Prolargin — P51888 (reviewed: P51888)

Alternative names: Proline-arginine-rich end leucine-rich repeat protein

All UniProt accessions (1): P51888

UniProt curated annotations — full annotation on UniProt →

Function. May anchor basement membranes to the underlying connective tissue.

Subunit / interactions. Binds the basement membrane heparan sulfate proteoglycan perlecan and triple helical collagens type I and type II.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Connective tissue.

Post-translational modifications. Glycosylated; contains heparan sulfate.

Domain organisation. The basic N-terminal Arg/Pro-rich region binds heparin and heparan sulfate. Binds collagens type I and type II through its leucine-rich repeat domain.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.

RefSeq proteins (2): NP_002716, NP_958505 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050333	SLRP	Family

Pfam: PF13855

UniProt features (26 total): repeat 12, glycosylation site 4, sequence variant 4, compositionally biased region 2, signal peptide 1, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51888-F1	86.64	0.71

Functional residue map

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

Disulfide bonds (1): 332–373

Glycosylation sites (4): 124, 289, 320, 327

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-2022857	Keratan sulfate degradation
R-HSA-3656225	Defective CHST6 causes MCDC1
R-HSA-3656243	Defective ST3GAL3 causes MCT12 and EIEE15
R-HSA-3656244	Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)

MSigDB gene sets: 177 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, JAEGER_METASTASIS_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, GOBP_CELLULAR_SENESCENCE, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, MARTINEZ_RB1_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN

GO Biological Process (2): skeletal system development (GO:0001501), cellular senescence (GO:0090398)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), heparin binding (GO:0008201), extracellular matrix structural constituent conferring compression resistance (GO:0030021), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), extracellular vesicle (GO:1903561)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	3
Keratan sulfate/keratin metabolism	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
cellular process	1
cellular response to stress	1
structural molecule activity	1
extracellular matrix	1
glycosaminoglycan binding	1
sulfur compound binding	1
extracellular matrix structural constituent	1
binding	1
cellular anatomical structure	1
Golgi apparatus	1
intracellular organelle lumen	1
external encapsulating structure	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRELP	B4GALT2	O60909	763
PRELP	B4GALT3	O60512	763
PRELP	HSPG2	P98160	760
PRELP	DPT	Q07507	714
PRELP	POSTN	Q15063	659
PRELP	CHAD	O15335	588
PRELP	HAPLN1	P10915	580
PRELP	BGN	P13247	561
PRELP	CILP	O75339	559
PRELP	THBS2	P35442	554
PRELP	OGN	P20774	549
PRELP	COL12A1	Q99715	542
PRELP	ACAN	P16112	537
PRELP	ASPN	Q9BXN1	535
PRELP	AGRN	O00468	528

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PRELP	AMD1	psi-mi:“MI:0914”(association)	0.530
PRELP	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
ACKR2	TMEM223	psi-mi:“MI:0914”(association)	0.350
PRELP	CLGN	psi-mi:“MI:0914”(association)	0.350
PRELP	IL12RB1	psi-mi:“MI:0914”(association)	0.350
	PRELP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (42): TSEN2 (Affinity Capture-MS), AMD1 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), Nid2 (Reconstituted Complex), TRIM68 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), AMD1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS)

ESM2 similar proteins: O02678, O15335, O35367, O42235, O46390, O46403, O46542, O55226, O60938, O62702, O70210, O75094, O94813, P07585, P19879, P20774, P21793, P21809, P21810, P28653, P28654, P28675, P47853, P51887, P51888, P82963, Q01129, Q27972, Q28888, Q29393, Q3ZBN5, Q5R1V9, Q5RBL2, Q5RI43, Q8MJF1, Q99MQ4, Q9BXN1, Q9DE65, Q9DE66, Q9DE68

Diamond homologs: A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, E7FE13, F1MLX5, G5EFX6, O02678, O02833, O35367, O46378, O46379, O46542, O60938, O62702, O75093, O75094, O88279, O88280, O94813, P07359, P07585, P21793, P24014, P28654, P28675, P35858, P35859, P51884, P51885, P51886, P51888, P51890, P58874, P59034, P59035, P70186, P70389, P83286

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

412 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203484154:GAGA:G	donor_gain	1.0000
1:203484156:GA:G	donor_gain	1.0000
1:203484158:G:GG	donor_gain	1.0000
1:203486704:A:AG	acceptor_gain	1.0000
1:203486705:G:GG	acceptor_gain	1.0000
1:203483163:CTGCA:C	acceptor_loss	0.9900
1:203483164:TGCAG:T	acceptor_loss	0.9900
1:203483165:GCAGG:G	acceptor_loss	0.9900
1:203483166:CA:C	acceptor_loss	0.9900
1:203483167:A:AC	acceptor_loss	0.9900
1:203483167:A:AG	acceptor_gain	0.9900
1:203483167:AG:A	acceptor_gain	0.9900
1:203483168:G:GA	acceptor_gain	0.9900
1:203483168:G:GT	acceptor_loss	0.9900
1:203483168:GG:G	acceptor_gain	0.9900
1:203483168:GGT:G	acceptor_gain	0.9900
1:203483168:GGTGC:G	acceptor_gain	0.9900
1:203485773:GA:G	donor_gain	0.9900
1:203485774:A:G	donor_gain	0.9900
1:203486701:C:A	acceptor_gain	0.9900
1:203486701:CGTA:C	acceptor_loss	0.9900
1:203486702:GTA:G	acceptor_loss	0.9900
1:203486703:TAG:T	acceptor_loss	0.9900
1:203486705:GA:G	acceptor_gain	0.9900
1:203486705:GAA:G	acceptor_gain	0.9900
1:203486705:GAAA:G	acceptor_gain	0.9900
1:203486705:GAAAT:G	acceptor_gain	0.9900
1:203481618:G:T	donor_gain	0.9800
1:203483167:AGGT:A	acceptor_gain	0.9800
1:203483168:GGTG:G	acceptor_gain	0.9800

AlphaMissense

2509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203483450:G:A	C89Y	1.000
1:203483451:T:G	C89W	1.000
1:203483520:C:A	N112K	1.000
1:203483520:C:G	N112K	1.000
1:203483711:T:C	L176P	1.000
1:203484131:T:C	L316P	1.000
1:203486796:T:C	L355P	1.000
1:203483401:T:C	C73R	0.999
1:203483413:T:A	C77S	0.999
1:203483413:T:C	C77R	0.999
1:203483414:G:C	C77S	0.999
1:203483415:C:G	C77W	0.999
1:203483419:T:C	C79R	0.999
1:203483449:T:A	C89S	0.999
1:203483449:T:C	C89R	0.999
1:203483450:G:C	C89S	0.999
1:203483450:G:T	C89F	0.999
1:203483510:T:C	L109P	0.999
1:203483519:A:T	N112I	0.999
1:203483592:C:A	N136K	0.999
1:203483592:C:G	N136K	0.999
1:203483664:C:A	N160K	0.999
1:203483664:C:G	N160K	0.999
1:203483717:T:C	L178P	0.999
1:203483726:A:T	N181I	0.999
1:203483727:C:A	N181K	0.999
1:203483727:C:G	N181K	0.999
1:203483783:T:C	L200P	0.999
1:203483789:T:C	L202P	0.999
1:203483799:C:A	N205K	0.999

dbSNP variants (sampled 300 via entrez): RS1000028993 (1:203481954 A>C), RS1000067461 (1:203478128 C>T), RS1000473430 (1:203477397 G>A), RS1000998171 (1:203489782 C>A), RS1001174512 (1:203488684 G>T), RS1001663070 (1:203487291 C>A), RS1002003470 (1:203488502 A>C), RS1002276489 (1:203489695 G>A), RS1002327409 (1:203489435 T>C), RS1002409850 (1:203476667 G>A,C), RS1002421223 (1:203476358 C>T), RS1002524967 (1:203484179 G>A), RS1002844743 (1:203480318 A>G), RS1002955455 (1:203491035 A>C,G), RS1003329127 (1:203490945 A>G)

Disease associations

OMIM: gene MIM:601914 | 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
GCST010219_4	Attention deficit hyperactivity disorder (inattention symptoms)	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	increases methylation	2
deoxynivalenol	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
incobotulinumtoxinA	increases expression	1
Panobinostat	increases expression, affects cotreatment	1
Benzo(a)pyrene	affects expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Methylprednisolone	increases expression	1
Nickel	decreases expression	1
Prednisolone	increases expression	1
T-2 Toxin	decreases expression	1
Vitamin E	increases expression	1
Zinc	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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