WFDC3

Summary

WFDC3 (WAP four-disulfide core domain 3, HGNC:15957) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 3 (Q8IUB2).

This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. The encoded protein contains four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined.

Source: NCBI Gene 140686 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_080614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15957
Approved symbol	WFDC3
Name	WAP four-disulfide core domain 3
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ447F3.3, WAP14
Ensembl gene	ENSG00000124116
Ensembl biotype	protein_coding
Entrez	140686

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding_CDS_not_defined, 4 protein_coding, 1 retained_intron

ENST00000243938, ENST00000337205, ENST00000372630, ENST00000372632, ENST00000462017, ENST00000465935, ENST00000467679, ENST00000471401, ENST00000474942, ENST00000481847, ENST00000487343, ENST00000490877, ENST00000493693

RefSeq mRNA: 1 — MANE Select: NM_080614 NM_080614

CCDS: CCDS33478

Canonical transcript exons

ENST00000243938 — 7 exons

Exon	Start	End
ENSE00001313024	45791832	45791883
ENSE00001693288	45789894	45789982
ENSE00003460567	45787836	45787982
ENSE00003520672	45775417	45775602
ENSE00003588714	45777075	45777209
ENSE00003614412	45774213	45774444
ENSE00003635993	45788931	45789059

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 97.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5072 / max 95.1789, expressed in 182 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187479	0.1720	42
187477	0.1663	51
187476	0.1242	33
187472	0.0294	13
187478	0.0153	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.78	gold quality
left testis	UBERON:0004533	94.78	gold quality
right testis	UBERON:0004534	94.52	gold quality
testis	UBERON:0000473	92.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.76	gold quality
upper arm skin	UBERON:0004263	86.89	silver quality
skin of leg	UBERON:0001511	85.05	gold quality
skin of abdomen	UBERON:0001416	83.73	gold quality
cartilage tissue	UBERON:0002418	83.59	gold quality
zone of skin	UBERON:0000014	83.16	gold quality
adult organism	UBERON:0007023	81.07	gold quality
right uterine tube	UBERON:0001302	80.42	gold quality
smooth muscle tissue	UBERON:0001135	78.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.66	gold quality
mucosa of transverse colon	UBERON:0004991	77.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.48	gold quality
right coronary artery	UBERON:0001625	76.41	gold quality
granulocyte	CL:0000094	76.33	gold quality
monocyte	CL:0000576	75.28	gold quality
vena cava	UBERON:0004087	75.14	gold quality
leukocyte	CL:0000738	74.80	gold quality
rectum	UBERON:0001052	74.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.57	gold quality
lower esophagus	UBERON:0013473	74.51	gold quality
nasal cavity epithelium	UBERON:0005384	74.22	gold quality
fundus of stomach	UBERON:0001160	74.06	gold quality
upper leg skin	UBERON:0004262	73.90	gold quality
epithelial cell of pancreas	CL:0000083	73.85	gold quality
body of stomach	UBERON:0001161	73.73	gold quality
transverse colon	UBERON:0001157	73.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting WFDC3, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-5002-3P	95.75	67.04	542
HSA-MIR-371B-3P	94.48	66.59	345
HSA-MIR-6879-3P	93.93	64.00	759
HSA-MIR-425-3P	93.06	63.65	68

Literature-anchored findings (GeneRIF, showing 1)

• High WFDC3 gene expression is associated with poor prognosis and reduced immune cells infiltration in pancreatic adenocarcinoma: A study using the TCGA database and bioinformatics analysis. (PMID:37861515)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc3	ENSMUSG00000076434
rattus_norvegicus	Wfdc3	ENSRNOG00000042162
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC11 (ENSG00000180083), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

WAP four-disulfide core domain protein 3 — Q8IUB2 (reviewed: Q8IUB2)

Alternative names: Putative protease inhibitor WAP14

All UniProt accessions (4): Q8IUB2, F2Z2G4, F2Z2G5, H0Y2V5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Ubiquitously expressed.

RefSeq proteins (1): NP_542181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008197	WAP_dom	Domain
IPR036645	Elafin-like_sf	Homologous_superfamily
IPR050514	WAP_four-disulfide_core	Family

Pfam: PF00095

UniProt features (28 total): disulfide bond 16, domain 4, sequence variant 2, sequence conflict 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUB2-F1	73.37	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 (16): 44–56, 50–65, 76–102, 85–106, 89–101, 95–110, 126–150, 133–154, 137–149, 143–158, 170–195, 178–199, 182–194, 188–203, 33–57, 40–61

Glycosylation sites (2): 107, 217

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): ATF_B, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, AP2_Q3, CREB_Q4, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, ATF1_Q6, GOBP_HUMORAL_IMMUNE_RESPONSE, ATF3_Q6, CREB_Q2_01, RFX1_02, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, ATF_01, CREBP1CJUN_01, CREB_01, SCGGAAGY_ELK1_02

GO Biological Process (2): antibacterial humoral response (GO:0019731), innate immune response (GO:0045087)

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antimicrobial humoral response	1
defense response to bacterium	1
immune response	1
defense response to symbiont	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC3	WFDC10B	Q8IUB3	657
WFDC3	WFDC13	Q8IUB5	623
WFDC3	DUX4L2	P0CJ85	606
WFDC3	WFDC10A	Q9H1F0	598
WFDC3	WFDC5	Q8TCV5	545
WFDC3	SPINT4	Q6UDR6	544
WFDC3	WFDC8	Q8IUA0	544
WFDC3	TRIM43	Q96BQ3	511
WFDC3	TRIM36	Q9NQ86	511
WFDC3	WFDC12	Q8WWY7	508
WFDC3	SNX21	Q969T3	506
WFDC3	DNTTIP1	Q9H147	504
WFDC3	SPATA25	Q9BR10	498
WFDC3	ZSWIM1	Q9BR11	490
WFDC3	PRAMEF6	Q5VXH4	479

IntAct

9 interactions, top by confidence:

A	B	Type	Score
LCE1F	WFDC3	psi-mi:“MI:0915”(physical association)	0.560
GET3	WFDC3	psi-mi:“MI:0915”(physical association)	0.560
WFDC3	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
WFDC3	MICA	psi-mi:“MI:0915”(physical association)	0.400
LCE1F	WFDC3	psi-mi:“MI:0915”(physical association)	0.000
GET3	WFDC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): ASNA1 (Two-hybrid), LCE1F (Two-hybrid), MICA (Affinity Capture-MS)

ESM2 similar proteins: A2A5H7, A4H215, A4H216, A4H217, A4H218, A4H235, A4H236, A4K2M5, A4K2P7, A4K2S3, A4K2T2, A4K2U0, A4K2W7, A4K2X5, A4K2Y3, A6NCL2, B4X8D9, B5G6H1, B5G6H2, B5G6H3, B5G6H5, B5L5N1, B5L5N2, B5L5N3, B5L5N4, B5L5P0, B5L5P2, B5L5P3, B5L5P7, O46655, P03973, P09412, P09837, P14730, P22298, P80392, P97430, Q03191, Q07654, Q14AE4

Diamond homologs: A7X4I7, A7X4J4, A7X4K1, A7X4K7, A7X4L4, O70280, P00993, P14730, P60589, Q4KUS1, Q6NUX0, Q8CHN3, Q8IUB2, Q9DAU7, Q9N0L8, B5G6G7, B5G6G8, B5G6G9, B5G6H0, B5G6H1, B5G6H2, B5G6H3, B5G6H4, B5G6H5, B5KGY9, B5L5M9, B5L5N1, B5L5N2, B5L5N3, B5L5N4, B5L5N6, B5L5P0, B5L5P2, B5L5P3, B5L5P4, B5L5P5, B5L5P6, B5L5P7, B5L5P8, B5L5P9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1083 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45775600:GCCC:G	acceptor_loss	1.0000
20:45775601:CCCTG:C	acceptor_loss	1.0000
20:45775602:CCTGT:C	acceptor_loss	1.0000
20:45775603:CT:C	acceptor_loss	1.0000
20:45775411:ACTC:A	donor_loss	0.9900
20:45775412:CTCA:C	donor_loss	0.9900
20:45775413:TCA:T	donor_loss	0.9900
20:45775414:CA:C	donor_loss	0.9900
20:45775415:A:AC	donor_gain	0.9900
20:45775416:C:CC	donor_gain	0.9900
20:45775416:C:CT	donor_loss	0.9900
20:45775598:CCGCC:C	acceptor_gain	0.9900
20:45775599:CGCC:C	acceptor_gain	0.9900
20:45775599:CGCCC:C	acceptor_gain	0.9900
20:45775601:CC:C	acceptor_gain	0.9900
20:45775602:CC:C	acceptor_gain	0.9900
20:45775603:C:CC	acceptor_gain	0.9900
20:45775604:T:G	acceptor_loss	0.9900
20:45788929:AC:A	donor_gain	0.9900
20:45788930:CC:C	donor_gain	0.9900
20:45791831:CAAGG:C	donor_gain	0.9900
20:45791852:T:A	donor_gain	0.9900
20:45774443:CT:C	acceptor_gain	0.9800
20:45775600:GCC:G	acceptor_gain	0.9800
20:45775601:CCC:C	acceptor_gain	0.9800
20:45775615:C:CT	acceptor_gain	0.9800
20:45791746:C:A	donor_gain	0.9800
20:45791775:CA:C	donor_gain	0.9800
20:45791830:A:AC	donor_gain	0.9800
20:45791831:C:CC	donor_gain	0.9800

AlphaMissense

1506 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45775490:G:C	F202L	0.889
20:45775490:G:T	F202L	0.889
20:45775492:A:G	F202L	0.889
20:45775551:C:G	C182S	0.868
20:45775552:A:T	C182S	0.868
20:45775515:C:G	C194S	0.862
20:45775516:A:T	C194S	0.862
20:45775533:C:G	C188S	0.829
20:45775534:A:T	C188S	0.829
20:45777124:T:A	K148N	0.825
20:45777124:T:G	K148N	0.825
20:45777158:C:G	C137S	0.824
20:45777159:A:T	C137S	0.824
20:45777122:C:G	C149S	0.819
20:45777123:A:T	C149S	0.819
20:45777140:C:G	C143S	0.817
20:45777141:A:T	C143S	0.817
20:45775552:A:G	C182R	0.809
20:45775563:C:G	C178S	0.808
20:45775564:A:T	C178S	0.808
20:45775512:C:G	C195S	0.805
20:45775513:A:T	C195S	0.805
20:45775500:C:G	C199S	0.799
20:45775501:A:T	C199S	0.799
20:45775516:A:G	C194R	0.782
20:45775587:C:G	C170S	0.777
20:45775588:A:T	C170S	0.777
20:45775551:C:T	C182Y	0.776
20:45775488:C:G	C203S	0.774
20:45775489:A:T	C203S	0.774

dbSNP variants (sampled 300 via entrez): RS1000083840 (20:45780758 AGTT>A), RS1000155760 (20:45784133 G>A), RS1000167515 (20:45776456 A>G), RS1000176945 (20:45780196 C>T), RS1000475418 (20:45776920 C>G,T), RS1000505040 (20:45774998 C>A,G,T), RS1000515895 (20:45778423 C>T), RS1000633272 (20:45785250 A>C), RS1000676470 (20:45792716 C>G,T), RS1000722455 (20:45783823 A>G,T), RS1000728558 (20:45792447 C>G,T), RS1001085497 (20:45788646 T>C,G), RS1001453331 (20:45788925 A>T), RS1001531249 (20:45781470 C>T), RS1001593400 (20:45780930 G>A)

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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
NSC 689534	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cytarabine	decreases expression	1
Oxygen	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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