WFDC5

Summary

WFDC5 (WAP four-disulfide core domain 5, HGNC:20477) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 5 (Q8TCV5). Putative acid-stable proteinase inhibitor.

This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. Most WFDC proteins contain only one WFDC domain, and this encoded protein contains two WFDC domains. 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 centromeric cluster.

Source: NCBI Gene 149708 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_145652

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20477
Approved symbol	WFDC5
Name	WAP four-disulfide core domain 5
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	WAP1, dJ211D12.5
Ensembl gene	ENSG00000175121
Ensembl biotype	protein_coding
OMIM	605161
Entrez	149708

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000307971, ENST00000372789

RefSeq mRNA: 2 — MANE Select: NM_145652 NM_001395506, NM_145652

CCDS: CCDS33475

Canonical transcript exons

ENST00000372789 — 4 exons

Exon	Start	End
ENSE00001177930	45110635	45110775
ENSE00001458652	45110400	45110540
ENSE00003978124	45114999	45115174
ENSE00003978125	45109463	45110013

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 98.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2991 / max 101.7781, expressed in 64 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187382	0.2660	62
187381	0.0173	8
187383	0.0159	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	98.82	gold quality
skin of abdomen	UBERON:0001416	97.56	gold quality
skin of leg	UBERON:0001511	97.16	gold quality
upper leg skin	UBERON:0004262	97.15	gold quality
zone of skin	UBERON:0000014	96.96	gold quality
nipple	UBERON:0002030	96.22	gold quality
penis	UBERON:0000989	95.52	gold quality
skin of hip	UBERON:0001554	94.33	gold quality
mammalian vulva	UBERON:0000997	94.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.77	gold quality
gingival epithelium	UBERON:0001949	84.67	gold quality
gingiva	UBERON:0001828	83.26	gold quality
sperm	CL:0000019	74.49	silver quality
lower esophagus mucosa	UBERON:0035834	74.16	gold quality
esophagus mucosa	UBERON:0002469	72.12	gold quality
esophagus squamous epithelium	UBERON:0006920	66.43	silver quality
pancreatic ductal cell	CL:0002079	64.22	silver quality
oral cavity	UBERON:0000167	64.05	gold quality
tonsil	UBERON:0002372	62.30	gold quality
vagina	UBERON:0000996	60.42	gold quality
palpebral conjunctiva	UBERON:0001812	57.16	silver quality
left ventricle myocardium	UBERON:0006566	56.35	gold quality
left testis	UBERON:0004533	55.49	gold quality
epithelial cell of pancreas	CL:0000083	55.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.16	gold quality
esophagus	UBERON:0001043	55.04	gold quality
ileal mucosa	UBERON:0000331	55.02	silver quality
body of tongue	UBERON:0011876	54.57	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
seminal vesicle	UBERON:0000998	54.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.59

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• analysis of promoter of mutated human whey acidic protein (WAP) gene (PMID:16462094)
• C-terminal domain of the nuclear factor I-B2 isoform is glycosylated and transactivates the WAP gene in tumor cells (PMID:17511965)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc5	ENSMUSG00000040154
rattus_norvegicus	Wfdc5	ENSRNOG00000013760
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC3 (ENSG00000124116), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC11 (ENSG00000180083), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

WAP four-disulfide core domain protein 5 — Q8TCV5 (reviewed: Q8TCV5)

Alternative names: Putative protease inhibitor WAP1, p53-responsive gene 5 protein

All UniProt accessions (1): Q8TCV5

UniProt curated annotations — full annotation on UniProt →

Function. Putative acid-stable proteinase inhibitor.

Subcellular location. Secreted.

Induction. By p53/TP53.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCV5-1	1	yes
Q8TCV5-2	2

RefSeq proteins (2): NP_001382435, NP_663627* (*=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 (15 total): disulfide bond 8, domain 2, signal peptide 1, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCV5-F1	68.13	0.32

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 (8): 96–108, 102–117, 34–62, 41–66, 49–61, 55–70, 81–109, 88–113

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, PEREZ_TP63_TARGETS, GGGTGGRR_PAX4_03, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_HUMORAL_IMMUNE_RESPONSE, PEREZ_TP53_AND_TP63_TARGETS, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, RICKMAN_HEAD_AND_NECK_CANCER_C, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOBP_RESPONSE_TO_BACTERIUM, GOMF_ENZYME_REGULATOR_ACTIVITY, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN

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

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC5	WFDC12	Q8WWY7	967
WFDC5	ELF5	Q9UKW6	826
WFDC5	GADD45GIP1	Q8TAE8	715
WFDC5	SEMG2	Q02383	568
WFDC5	SEMG1	P04279	549
WFDC5	PI3	P19957	545
WFDC5	WFDC3	Q8IUB2	545
WFDC5	GPR87	Q9BY21	508
WFDC5	WFDC8	Q8IUA0	506
WFDC5	C5orf46	Q6UWT4	479
WFDC5	ELF3	P78545	436
WFDC5	ITGB3	P05106	426
WFDC5	ADGRF4	Q8IZF3	423
WFDC5	TCHP	Q9BT92	423
WFDC5	CDKN1A	P38936	421

IntAct

20 interactions, top by confidence:

A	B	Type	Score
ASPH	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
SGTA	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
BRK1	WFDC5	psi-mi:“MI:0915”(physical association)	0.560
ATG16L1		psi-mi:“MI:0914”(association)	0.350
WFDC5	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): WFDC5 (Two-hybrid), WFDC5 (Two-hybrid), WFDC5 (Two-hybrid), KLHL38 (Two-hybrid), ASPH (Two-hybrid), WFDC5 (Affinity Capture-Western), WFDC5 (Affinity Capture-Western), SMC1A (Affinity Capture-Western), STAG2 (Affinity Capture-Western), RAD21 (Affinity Capture-Western), PDS5B (Affinity Capture-Western), PDS5A (Affinity Capture-Western), WFDC5 (Affinity Capture-Western), WFDC5 (Affinity Capture-Western), WFDC5 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GTK5, A4H220, A4H221, A4H222, A4H223, A4K2M6, A4K2P0, A4K2P8, A4K2S4, A4K2T3, A4K2U1, A4K2W8, A4K2X6, A4K2Y4, A6NMD0, F2Z3F1, P04610, P05905, P05906, P05907, P05908, P0C8A9, P0DP71, P14138, P19552, P20893, P43359, Q1RN00, Q1WG82, Q30KK9, Q3B7M4, Q3UW43, Q5PR19, Q66H03, Q66HF0, Q6K1E7, Q6MG53, Q6NUN9, Q73370, Q765Z4

Diamond homologs: A4K2M5, A4K2N9, A4K2P7, A4K2Q7, A4K2R4, A4K2S3, A4K2S4, A4K2T2, A4K2U0, A4K2V3, A4K2W7, A4K2X5, A4K2Y3, Q6IE40, Q8TCV5, A4K2U1, A4K2X6, P03973, Q8IUA0, Q8CHN3, Q9DAU7, A4K2M6, A4K2P0, A4K2P8, A4K2R5, A4K2T3, A4K2V4, A4K2W8, A4K2Y4, O46655, P09837, P19957, Q8WWY7, B5L5N6, D4A2Z2, O95925, P97430, Q8BH89, Q9DA01, Q9JHY3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

488 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45114995:TCACC:T	donor_loss	1.0000
20:45114996:CAC:C	donor_loss	1.0000
20:45114997:A:T	donor_loss	1.0000
20:45114997:ACCT:A	donor_gain	1.0000
20:45114997:ACCTC:A	donor_gain	1.0000
20:45114998:CCTC:C	donor_gain	1.0000
20:45114998:CCTCC:C	donor_gain	1.0000
20:45115001:C:A	donor_gain	1.0000
20:45115008:T:TA	donor_gain	1.0000
20:45110009:TTAGC:T	acceptor_gain	0.9900
20:45110010:TAGC:T	acceptor_gain	0.9900
20:45110541:C:CC	acceptor_gain	0.9900
20:45114998:CCT:C	donor_gain	0.9900
20:45110683:T:TA	donor_gain	0.9800
20:45114997:A:AC	donor_gain	0.9800
20:45114998:C:CC	donor_gain	0.9800
20:45110014:C:CC	acceptor_gain	0.9700
20:45110015:T:G	acceptor_loss	0.9700
20:45110539:CA:C	acceptor_gain	0.9700
20:45111319:T:A	donor_gain	0.9700
20:45115000:T:TA	donor_gain	0.9700
20:45110399:CCT:C	donor_gain	0.9600
20:45110536:CTTCA:C	acceptor_gain	0.9600
20:45110537:TTCA:T	acceptor_gain	0.9600
20:45112617:T:C	acceptor_gain	0.9600
20:45114992:CACT:C	donor_loss	0.9600
20:45114993:ACTC:A	donor_loss	0.9600
20:45110012:GC:G	acceptor_gain	0.9500
20:45110013:CC:C	acceptor_gain	0.9500
20:45110011:AGC:A	acceptor_gain	0.9400

AlphaMissense

797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45110472:C:G	D99H	0.995
20:45110480:C:G	C96S	0.994
20:45110481:A:T	C96S	0.994
20:45110697:C:G	C55S	0.994
20:45110698:A:T	C55S	0.994
20:45110706:T:A	D52V	0.994
20:45110707:C:G	D52H	0.994
20:45110715:C:G	C49S	0.994
20:45110716:A:T	C49S	0.994
20:45110471:T:A	D99V	0.993
20:45110462:C:G	C102S	0.991
20:45110463:A:T	C102S	0.991
20:45110471:T:G	D99A	0.991
20:45110706:T:G	D52A	0.990
20:45110444:C:G	C108S	0.989
20:45110445:A:T	C108S	0.989
20:45110652:C:G	C70S	0.989
20:45110653:A:T	C70S	0.989
20:45110471:T:C	D99G	0.988
20:45110660:G:C	F67L	0.988
20:45110660:G:T	F67L	0.988
20:45110662:A:G	F67L	0.988
20:45110679:C:G	C61S	0.988
20:45110680:A:T	C61S	0.988
20:45110760:C:G	C34S	0.988
20:45110761:A:T	C34S	0.988
20:45110417:C:G	C117S	0.987
20:45110418:A:T	C117S	0.987
20:45110470:G:C	D99E	0.987
20:45110470:G:T	D99E	0.987

dbSNP variants (sampled 300 via entrez): RS1000040854 (20:45111502 C>A,T), RS1000165688 (20:45116974 T>C), RS1000967420 (20:45117454 C>T), RS1001082026 (20:45117093 G>A), RS1001844915 (20:45110400 C>A,T), RS1001877450 (20:45110623 G>A,C), RS1002349768 (20:45116525 C>T), RS1002906666 (20:45112263 G>A,C), RS1003841540 (20:45114107 G>A), RS1003893807 (20:45114465 A>G), RS1003954583 (20:45110678 G>A), RS1003968224 (20:45116596 T>C), RS1004264392 (20:45110880 C>A,T), RS1004760501 (20:45114306 A>C), RS1005532418 (20:45115407 T>C)

Disease associations

OMIM: gene MIM:605161 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007456_3	Eye color (hue)	2.000000e-08
GCST008103_18	Bipolar disorder	1.000000e-08
GCST008103_27	Bipolar disorder	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009764	eye colour measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Dactinomycin	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Formaldehyde	increases expression	1
Silicon Dioxide	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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