PAPLN

Summary

PAPLN (papilin, proteoglycan like sulfated glycoprotein, HGNC:19262) is a protein-coding gene on chromosome 14q24.2, encoding Papilin (O95428).

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in extracellular matrix organization and nervous system development. Predicted to be located in basement membrane.

Source: NCBI Gene 89932 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 284 total
• MANE Select transcript: NM_001365906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19262
Approved symbol	PAPLN
Name	papilin, proteoglycan like sulfated glycoprotein
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC50452
Ensembl gene	ENSG00000100767
Ensembl biotype	protein_coding
OMIM	617785
Entrez	89932

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216658, ENST00000340738, ENST00000554301, ENST00000554314, ENST00000554527, ENST00000555035, ENST00000555123, ENST00000555445, ENST00000555700, ENST00000557061, ENST00000559759, ENST00000644200, ENST00000864046, ENST00000911606, ENST00000911607, ENST00000911608, ENST00000957729, ENST00000957730, ENST00000957731, ENST00000957732, ENST00000957733

RefSeq mRNA: 3 — MANE Select: NM_001365906 NM_001365906, NM_001365907, NM_173462

CCDS: CCDS32114, CCDS91898, CCDS91899

Canonical transcript exons

ENST00000644200 — 27 exons

Exon	Start	End
ENSE00000000097	73237506	73237592
ENSE00000659146	73251486	73251566
ENSE00001597182	73252018	73252141
ENSE00001637972	73249984	73250114
ENSE00001639800	73254513	73254695
ENSE00001663645	73244644	73244759
ENSE00001664286	73260709	73260829
ENSE00001671222	73245636	73245696
ENSE00001677201	73261156	73261294
ENSE00001684182	73246073	73246175
ENSE00001685700	73250907	73251030
ENSE00001702564	73252649	73252775
ENSE00001713128	73239773	73239832
ENSE00001732545	73251664	73251836
ENSE00001740504	73253754	73253961
ENSE00001783077	73254877	73255018
ENSE00001786098	73258979	73259059
ENSE00001796157	73259269	73259545
ENSE00003482126	73265370	73265507
ENSE00003488716	73263645	73263782
ENSE00003506461	73266501	73266628
ENSE00003532811	73268557	73268723
ENSE00003609076	73264588	73264726
ENSE00003619722	73262350	73262827
ENSE00003681308	73266723	73266831
ENSE00003690670	73264211	73264335
ENSE00003824227	73272495	73274623

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 96.09.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2969 / max 66.7676, expressed in 704 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140520	3.0874	692
140521	0.2095	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	96.09	gold quality
tendon of biceps brachii	UBERON:0008188	95.60	gold quality
decidua	UBERON:0002450	94.54	gold quality
trigeminal ganglion	UBERON:0001675	94.43	gold quality
dorsal root ganglion	UBERON:0000044	94.00	gold quality
kidney epithelium	UBERON:0004819	92.78	gold quality
mucosa of stomach	UBERON:0001199	92.15	gold quality
metanephros cortex	UBERON:0010533	92.01	gold quality
sural nerve	UBERON:0015488	91.43	gold quality
upper arm skin	UBERON:0004263	91.20	gold quality
left uterine tube	UBERON:0001303	91.02	gold quality
lymph node	UBERON:0000029	90.91	gold quality
spleen	UBERON:0002106	90.66	gold quality
cortex of kidney	UBERON:0001225	90.59	gold quality
endometrium	UBERON:0001295	90.55	gold quality
left lobe of thyroid gland	UBERON:0001120	90.33	gold quality
right lobe of thyroid gland	UBERON:0001119	90.22	gold quality
adult mammalian kidney	UBERON:0000082	90.06	gold quality
renal medulla	UBERON:0000362	89.91	gold quality
thyroid gland	UBERON:0002046	89.91	gold quality
superficial temporal artery	UBERON:0001614	89.41	gold quality
body of uterus	UBERON:0009853	89.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.24	gold quality
kidney	UBERON:0002113	89.09	gold quality
caput epididymis	UBERON:0004358	88.65	gold quality
endocervix	UBERON:0000458	88.63	gold quality
layer of synovial tissue	UBERON:0007616	88.57	gold quality
uterus	UBERON:0000995	88.56	gold quality
right ovary	UBERON:0002118	87.96	gold quality
skin of leg	UBERON:0001511	87.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting PAPLN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-7-1-3P	99.91	71.53	4384

Literature-anchored findings (GeneRIF, showing 1)

• ADAMTS-2, collagen type-1, TIMP-3 and papilin levels of the uterosacral ligament play essential roles in the etiopathogenesis of pelvic organ prolapse among postmenopausal women without stress urinary incontinence. (PMID:30388611)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	paplna	ENSDARG00000027867
danio_rerio	paplnb	ENSDARG00000042186
mus_musculus	Papln	ENSMUSG00000021223
rattus_norvegicus	Papln	ENSRNOG00000009448

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

Papilin — O95428 (reviewed: O95428)

All UniProt accessions (5): O95428, B5MDP7, G3V5P6, H0YJA1, H0YMM2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the papilin family.

Isoforms (6)

UniProt ID	Names	Canonical?
O95428-1	1	yes
O95428-2	2
O95428-5	5
O95428-6	6
O95428-3	3
O95428-4	4

RefSeq proteins (3): NP_001352835, NP_001352836, NP_775733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR002223	Kunitz_BPTI	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR010909	PLAC	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00014, PF00090, PF05986, PF07679, PF08686, PF13927, PF16626, PF19030, PF19236

UniProt features (52 total): disulfide bond 12, sequence variant 11, domain 10, splice variant 8, sequence conflict 4, region of interest 3, compositionally biased region 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95428-F1	67.18	0.14

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 (12): 38–74, 42–79, 53–64, 316–355, 320–360, 331–343, 754–804, 763–787, 779–800, 931–978, 1065–1112, 1154–1202

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, WHITEHURST_PACLITAXEL_SENSITIVITY, chr14q24, HNF4_DR1_Q3, HNF4_01, PPAR_DR1_Q2, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, PPARA_01, GOCC_BASEMENT_MEMBRANE, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, WGTTNNNNNAAA_UNKNOWN, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, COUP_DR1_Q6, GOMF_ENZYME_INHIBITOR_ACTIVITY

GO Biological Process (1): extracellular matrix organization (GO:0030198)

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): extracellular region (GO:0005576), basement membrane (GO:0005604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular structure organization	1
external encapsulating structure organization	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1
extracellular matrix	1

Protein interactions and networks

STRING

856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAPLN	FBN1	P35555	560
PAPLN	ZNF75D	P51815	478
PAPLN	ADGRA1	Q86SQ6	454
PAPLN	ARID5B	Q14865	453
PAPLN	ZNF511	Q8NB15	418
PAPLN	R3HCC1	Q9Y3T6	416
PAPLN	FAM149A	A5PLN7	410
PAPLN	AOPEP	Q8N6M6	405
PAPLN	PRPF3	O43395	384
PAPLN	DNAJC16	Q9Y2G8	355
PAPLN	IFNLR1	Q8IU57	354
PAPLN	TMEM160	Q9NX00	350
PAPLN	NGB	Q9NPG2	350
PAPLN	ADGB	Q8N7X0	350
PAPLN	MB	P02144	349
PAPLN	ELP4	Q96EB1	349

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CD200	PAPLN	psi-mi:“MI:0915”(physical association)	0.400
TFAP2C	PAPLN	psi-mi:“MI:0915”(physical association)	0.370
PAPLN	SDHB	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): B3GALTL (Affinity Capture-MS), KIF2C (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), THOP1 (Affinity Capture-MS), PKM (Affinity Capture-MS), PAPLN (Affinity Capture-MS), BCAT1 (Affinity Capture-MS), KIF2C (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), B3GALTL (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

Diamond homologs: A0N0X6, A2AJ76, A2CG49, A4IGL7, A4IIW9, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, G5EBF1, O75325, O95428, P0C6S8, P11627, P12960, P22063, P28685, P32004, P97924, Q02246, Q07409, Q09024, Q12860, Q290N5, Q32Q07, Q3UQ28, Q3URE9, Q3V1M1, Q5R482, Q61330, Q61809, Q62682, Q62845, Q63198, Q66HV9, Q69Z26, Q6AWJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	225
Likely benign	29
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4684 predictions. Top by Δscore:

Variant	Effect	Δscore
14:73239830:TCGG:T	donor_loss	1.0000
14:73239832:GGTG:G	donor_loss	1.0000
14:73239833:G:GG	donor_gain	1.0000
14:73239834:T:A	donor_loss	1.0000
14:73249982:A:AG	acceptor_gain	1.0000
14:73249983:G:GG	acceptor_gain	1.0000
14:73249983:GCC:G	acceptor_gain	1.0000
14:73249983:GCCC:G	acceptor_gain	1.0000
14:73249983:GCCCC:G	acceptor_gain	1.0000
14:73250110:GCCGG:G	donor_gain	1.0000
14:73250111:CCGGG:C	donor_loss	1.0000
14:73250112:CGGG:C	donor_loss	1.0000
14:73250113:GG:G	donor_gain	1.0000
14:73250114:GG:G	donor_gain	1.0000
14:73250115:G:GG	donor_gain	1.0000
14:73250116:T:A	donor_loss	1.0000
14:73250117:G:GG	donor_loss	1.0000
14:73251013:C:G	donor_gain	1.0000
14:73251556:G:GT	donor_gain	1.0000
14:73251565:GG:G	donor_gain	1.0000
14:73251565:GGGTG:G	donor_loss	1.0000
14:73251566:GG:G	donor_gain	1.0000
14:73251567:G:GG	donor_gain	1.0000
14:73251568:T:A	donor_loss	1.0000
14:73251659:C:CA	acceptor_gain	1.0000
14:73251660:GCAGC:G	acceptor_loss	1.0000
14:73251662:A:AG	acceptor_gain	1.0000
14:73251662:AGCT:A	acceptor_gain	1.0000
14:73251663:G:GG	acceptor_gain	1.0000
14:73251663:GC:G	acceptor_gain	1.0000

AlphaMissense

8301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:73266824:T:A	W1165R	0.998
14:73266824:T:C	W1165R	0.998
14:73266826:G:C	W1165C	0.997
14:73266826:G:T	W1165C	0.997
14:73246159:G:C	W106C	0.996
14:73246159:G:T	W106C	0.996
14:73262439:T:A	C779S	0.996
14:73262440:G:C	C779S	0.996
14:73265475:G:C	W1077C	0.995
14:73265475:G:T	W1077C	0.995
14:73249995:T:A	C116S	0.994
14:73249996:G:C	C116S	0.994
14:73250007:T:A	C120S	0.994
14:73250008:G:C	C120S	0.994
14:73262449:T:G	F782C	0.994
14:73244685:G:C	W32C	0.993
14:73244685:G:T	W32C	0.993
14:73246112:T:A	C91S	0.993
14:73246113:G:C	C91S	0.993
14:73251559:C:A	N221K	0.993
14:73251559:C:G	N221K	0.993
14:73262402:G:C	W766C	0.993
14:73262402:G:T	W766C	0.993
14:73262448:T:C	F782L	0.993
14:73262450:C:A	F782L	0.993
14:73262450:C:G	F782L	0.993
14:73262485:T:G	F794C	0.993
14:73262502:T:A	C800S	0.993
14:73262503:G:C	C800S	0.993
14:73244694:G:C	W35C	0.992

dbSNP variants (sampled 300 via entrez): RS1000047121 (14:73238611 G>T), RS1000089435 (14:73235229 C>A,T), RS1000154164 (14:73270250 CCGCGCT>C), RS1000282165 (14:73256336 G>A,T), RS1000335493 (14:73260226 C>A,T), RS1000441581 (14:73234124 C>T), RS1000476553 (14:73261103 C>T), RS1000541803 (14:73265882 G>T), RS1000649541 (14:73257367 C>T), RS1000818149 (14:73260452 G>T), RS1000910888 (14:73247261 A>G), RS1001020163 (14:73257538 G>A), RS1001057911 (14:73266148 G>A,T), RS1001074529 (14:73251404 T>C), RS1001239803 (14:73249289 A>T)

Disease associations

OMIM: gene MIM:617785 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004621_71	Red cell distribution width	2.000000e-10
GCST009284_2	Macroalbuminuria in type 1 diabetes	5.000000e-07
GCST009391_1980	Metabolite levels	1.000000e-06
GCST012256_15	SAPHO syndrome	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004285	albuminuria
EFO:0005058	tyrosine measurement

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
rs11628713	Toxicity	3	citalopram	Major Depressive Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11628713	PAPLN	3	0.00	1	citalopram

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	decreases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	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, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Air Pollutants	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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