WFDC13

Summary

WFDC13 (WAP four-disulfide core domain 13, HGNC:16131) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 13 (Q8IUB5). Putative acid-stable proteinase inhibitor.

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. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster.

Source: NCBI Gene 164237 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_172005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16131
Approved symbol	WFDC13
Name	WAP four-disulfide core domain 13
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ601O1.3, WAP13
Ensembl gene	ENSG00000168634
Ensembl biotype	protein_coding
Entrez	164237

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000305479

RefSeq mRNA: 1 — MANE Select: NM_172005 NM_172005

CCDS: CCDS13367

Canonical transcript exons

ENST00000305479 — 4 exons

Exon	Start	End
ENSE00001125074	45704444	45704594
ENSE00001302327	45705863	45705927
ENSE00001307120	45702038	45702211
ENSE00001320717	45707858	45708817

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 87.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1651 / max 236.5214, expressed in 15 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184934	0.1319	8
184933	0.0176	2
184935	0.0157	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	87.81	gold quality
corpus epididymis	UBERON:0004359	82.10	gold quality
secondary oocyte	CL:0000655	68.89	gold quality
caput epididymis	UBERON:0004358	59.05	silver quality
lateral nuclear group of thalamus	UBERON:0002736	58.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	57.63	gold quality
tendon of biceps brachii	UBERON:0008188	57.29	gold quality
urinary bladder	UBERON:0001255	52.15	gold quality
substantia nigra pars compacta	UBERON:0001965	51.72	gold quality
lateral globus pallidus	UBERON:0002476	47.74	gold quality
oocyte	CL:0000023	45.64	gold quality
upper leg skin	UBERON:0004262	45.48	silver quality
mucosa of stomach	UBERON:0001199	45.10	gold quality
lower esophagus mucosa	UBERON:0035834	44.90	silver quality
lower lobe of lung	UBERON:0008949	44.44	silver quality
tendon	UBERON:0000043	43.94	gold quality
skin of leg	UBERON:0001511	43.94	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
myocardium	UBERON:0002349	42.86	gold quality
vastus lateralis	UBERON:0001379	42.75	gold quality
quadriceps femoris	UBERON:0001377	42.68	gold quality
globus pallidus	UBERON:0001875	42.27	gold quality
colonic epithelium	UBERON:0000397	41.96	gold quality
zone of skin	UBERON:0000014	41.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.58	gold quality
medial globus pallidus	UBERON:0002477	41.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
middle temporal gyrus	UBERON:0002771	40.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting WFDC13, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-657	99.48	66.02	848
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6840-3P	98.68	65.95	1923

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc13	ENSMUSG00000067704
rattus_norvegicus		ENSRNOG00000084888
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC3 (ENSG00000124116), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC11 (ENSG00000180083), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

WAP four-disulfide core domain protein 13 — Q8IUB5 (reviewed: Q8IUB5)

All UniProt accessions (1): Q8IUB5

UniProt curated annotations — full annotation on UniProt →

Function. Putative acid-stable proteinase inhibitor.

Subcellular location. Secreted.

RefSeq proteins (1): NP_742002* (*=MANE)

Domains & families (InterPro)

UniProt features (6 total): disulfide bond 3, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUB5-F1	68.73	0.01

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 (3): 45–66, 49–61, 55–70

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOBP_RESPONSE_TO_BACTERIUM, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_ANTIBACTERIAL_HUMORAL_RESPONSE, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, MIR4795_3P, MIR126_5P, MIR203A_3P, MIR587

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

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC13	WFDC9	Q8NEX5	727
WFDC13	WFDC11	Q8NEX6	719
WFDC13	SPINT4	Q6UDR6	715
WFDC13	WFDC10A	Q9H1F0	637
WFDC13	WFDC3	Q8IUB2	623
WFDC13	WFDC10B	Q8IUB3	583
WFDC13	WFDC2	Q14508	523
WFDC13	WFDC6	Q9BQY6	475
WFDC13	DNTTIP1	Q9H147	458
WFDC13	RNASE13	Q5GAN3	452
WFDC13	WFDC8	Q8IUA0	451
WFDC13	SPINT3	P49223	434
WFDC13	DENND11	A4D1U4	394
WFDC13	TMEM123	Q8N131	393
WFDC13	WFDC1	Q9HC57	389

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MEOX2	WFDC13	psi-mi:“MI:0915”(physical association)	0.560
SGTA	WFDC13	psi-mi:“MI:0915”(physical association)	0.560
WFDC13	SGTA	psi-mi:“MI:0915”(physical association)	0.000
WFDC13	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): WFDC13 (Two-hybrid), WFDC13 (Two-hybrid)

ESM2 similar proteins: A2A5H7, A4H202, A4H203, A4H204, A4H225, A4H226, A4H227, A4H228, A4H253, A4H254, A4H255, P50704, P50705, P50707, P50708, P50713, P50714, Q30KJ3, Q30KJ7, Q30KK8, Q30KN4, Q30KP9, Q30KT5, Q32P86, Q32ZF7, Q32ZG2, Q32ZG3, Q32ZH2, Q32ZH6, Q3UW41, Q5DQQ6, Q5G865, Q5G866, Q5IAB9, Q5J602, Q6IE40, Q6IE41, Q6IV18, Q7Z7B8, Q8IUB3

Diamond homologs: Q5DQQ6, Q8IUB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

631 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45702212:G:GG	donor_gain	1.0000
20:45702156:G:GA	donor_gain	0.9900
20:45702210:GA:G	donor_gain	0.9900
20:45702240:G:T	donor_gain	0.9900
20:45703879:G:GT	donor_gain	0.9900
20:45704443:GA:G	acceptor_gain	0.9900
20:45705861:A:AG	acceptor_gain	0.9900
20:45705862:G:GG	acceptor_gain	0.9900
20:45705928:G:GG	donor_gain	0.9900
20:45702155:T:TA	donor_gain	0.9800
20:45702188:G:GT	donor_gain	0.9800
20:45702240:G:GT	donor_gain	0.9800
20:45704443:GAGT:G	acceptor_gain	0.9800
20:45705862:GA:G	acceptor_gain	0.9800
20:45704442:A:AG	acceptor_gain	0.9700
20:45704443:G:GG	acceptor_gain	0.9700
20:45704958:CA:C	donor_gain	0.9700
20:45705924:TTTT:T	donor_gain	0.9700
20:45702205:GTTC:G	donor_gain	0.9600
20:45702206:TTCT:T	donor_gain	0.9600
20:45703930:G:GG	donor_gain	0.9600
20:45704590:AACAG:A	donor_loss	0.9600
20:45704591:ACAGG:A	donor_loss	0.9600
20:45704593:AG:A	donor_loss	0.9600
20:45704595:GTA:G	donor_loss	0.9600
20:45704596:T:G	donor_loss	0.9600
20:45703929:A:AG	donor_gain	0.9500
20:45704571:A:T	acceptor_gain	0.9500
20:45705862:GAATC:G	acceptor_gain	0.9500
20:45702208:CTGA:C	donor_loss	0.9400

AlphaMissense

599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45704536:T:A	C61S	0.983
20:45704537:G:C	C61S	0.983
20:45704551:T:A	C66S	0.983
20:45704552:G:C	C66S	0.983
20:45704500:T:A	C49S	0.982
20:45704501:G:C	C49S	0.982
20:45704518:T:A	C55S	0.979
20:45704519:G:C	C55S	0.979
20:45704563:T:A	C70S	0.979
20:45704564:G:C	C70S	0.979
20:45704552:G:A	C66Y	0.976
20:45704555:G:T	G67V	0.973
20:45704551:T:C	C66R	0.971
20:45704469:C:G	C38W	0.970
20:45704467:T:A	C38S	0.968
20:45704468:G:C	C38S	0.968
20:45704502:T:G	C49W	0.968
20:45704554:G:T	G67W	0.968
20:45704552:G:T	C66F	0.967
20:45704488:T:A	C45S	0.966
20:45704489:G:C	C45S	0.966
20:45704536:T:C	C61R	0.966
20:45704538:C:G	C61W	0.966
20:45704519:G:A	C55Y	0.964
20:45704548:T:C	F65L	0.963
20:45704550:C:A	F65L	0.963
20:45704550:C:G	F65L	0.963
20:45704563:T:C	C70R	0.962
20:45704501:G:A	C49Y	0.959
20:45704500:T:C	C49R	0.958

dbSNP variants (sampled 300 via entrez): RS1000818625 (20:45703851 T>G), RS1000828863 (20:45707563 A>T), RS1000932052 (20:45707150 A>G), RS1001056750 (20:45700836 A>C,G), RS1002233434 (20:45704563 T>C,G), RS1002825296 (20:45701138 C>T), RS1002843903 (20:45704324 T>C,G), RS1002876234 (20:45707920 G>A), RS1002938814 (20:45704064 C>G,T), RS1003181966 (20:45706494 C>T), RS1003234938 (20:45706213 C>A), RS1003269316 (20:45702389 A>G), RS1003340686 (20:45707676 T>C), RS1004182552 (20:45702058 C>A,T), RS1004235134 (20:45701799 T>C)

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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Estradiol	decreases expression	1
Folic Acid	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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