WFDC9

Summary

WFDC9 (WAP four-disulfide core domain 9, HGNC:20380) is a protein-coding gene on chromosome 20q13.12, encoding Protein WFDC9 (Q8NEX5).

The WAP-type four-disulfide core (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 in many members of the WFDC domain family. This gene encodes a protein which contains a WFDC domain, and is thus a member of the WFDC domain family. This gene and several other gene family members are clustered at 20q13.12.

Source: NCBI Gene 259240 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_147198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20380
Approved symbol	WFDC9
Name	WAP four-disulfide core domain 9
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	WAP9, dJ688G8.2
Ensembl gene	ENSG00000180205
Ensembl biotype	protein_coding
Entrez	259240

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000326000

RefSeq mRNA: 1 — MANE Select: NM_147198 NM_147198

CCDS: CCDS13362

Canonical transcript exons

ENST00000326000 — 5 exons

Exon	Start	End
ENSE00001268256	45608663	45608810
ENSE00001268262	45614628	45614721
ENSE00001268267	45631203	45631284
ENSE00001268276	45607939	45608140
ENSE00001268285	45610091	45610239

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 99.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2555 / max 416.5289, expressed in 5 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187466	0.1835	3
187465	0.0529	3
187464	0.0119	1
187467	0.0071	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.59	gold quality
cauda epididymis	UBERON:0004360	98.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.16	gold quality
sperm	CL:0000019	84.52	gold quality
buccal mucosa cell	CL:0002336	77.41	gold quality
caput epididymis	UBERON:0004358	70.59	gold quality
epithelium of nasopharynx	UBERON:0001951	67.72	gold quality
oocyte	CL:0000023	65.21	silver quality
myocardium	UBERON:0002349	64.21	gold quality
lower lobe of lung	UBERON:0008949	62.24	silver quality
superficial temporal artery	UBERON:0001614	58.83	gold quality
trabecular bone tissue	UBERON:0002483	57.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.16	gold quality
gingival epithelium	UBERON:0001949	57.11	gold quality
secondary oocyte	CL:0000655	56.95	gold quality
nipple	UBERON:0002030	56.02	gold quality
esophagus squamous epithelium	UBERON:0006920	55.87	gold quality
cardia of stomach	UBERON:0001162	55.50	gold quality
gingiva	UBERON:0001828	55.08	gold quality
subthalamic nucleus	UBERON:0001906	54.69	gold quality
seminal vesicle	UBERON:0000998	54.53	silver quality
trigeminal ganglion	UBERON:0001675	54.13	gold quality
dorsal root ganglion	UBERON:0000044	54.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	54.03	gold quality
ventral tegmental area	UBERON:0002691	53.98	gold quality
germinal epithelium of ovary	UBERON:0001304	53.91	gold quality
dorsal plus ventral thalamus	UBERON:0001897	53.63	gold quality
layer of synovial tissue	UBERON:0007616	53.09	gold quality
saphenous vein	UBERON:0007318	53.06	gold quality
middle temporal gyrus	UBERON:0002771	53.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting WFDC9, 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-12124	99.68	69.17	2700
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-4433B-5P	95.91	66.56	727

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc9	ENSMUSG00000074594
rattus_norvegicus	Wfdc9	ENSRNOG00000031380
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC3 (ENSG00000124116), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC11 (ENSG00000180083), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

Protein WFDC9 — Q8NEX5 (reviewed: Q8NEX5)

All UniProt accessions (1): Q8NEX5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Miscellaneous. Although this protein was isolated in a region containing several WAP proteins and was defined as a WAP protein, it does not contain a classical WAP domain.

RefSeq proteins (1): NP_671731* (*=MANE)

Domains & families (InterPro)

UniProt features (3 total): signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEX5-F1	79.69	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, 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, MIR6830_5P

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

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC9	WFDC13	Q8IUB5	727
WFDC9	WFDC8	Q8IUA0	669
WFDC9	WFDC10A	Q9H1F0	651
WFDC9	SPINT4	Q6UDR6	571
WFDC9	SPINT3	P49223	542
WFDC9	WFDC2	Q14508	498
WFDC9	EDDM3A	Q14507	489
WFDC9	EDDM3B	P56851	488
WFDC9	DEFB118	Q96PH6	480
WFDC9	RNASE13	Q5GAN3	479
WFDC9	SPAG11A	Q6PDA7	449
WFDC9	LCN8	Q6JVE9	447
WFDC9	DEFB129	Q9H1M3	436
WFDC9	EPPIN	O95925	435
WFDC9	SEMG1	P04279	404

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MEOX2	WFDC9	psi-mi:“MI:0915”(physical association)	0.560
WFDC9	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
WFDC9	CTSC	psi-mi:“MI:0914”(association)	0.530
WFDC9	TXNL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): WFDC9 (Two-hybrid), CTSC (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), ZER1 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), TXNL1 (Affinity Capture-MS), CTSC (Affinity Capture-MS), ZER1 (Affinity Capture-MS), WFDC9 (Positive Genetic)

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: A2A5H7, Q3UW41, Q6IE41, Q8IUB3, Q8NEX5, Q8NEX6, Q9H1F0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

667 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45629660:G:GT	donor_gain	1.0000
20:45629903:GA:G	donor_gain	1.0000
20:45629905:G:GG	donor_gain	1.0000
20:45629897:G:GT	donor_gain	0.9900
20:45629900:GCAGA:G	donor_gain	0.9900
20:45629647:C:T	donor_gain	0.9800
20:45629661:A:T	donor_gain	0.9800
20:45610114:C:A	donor_gain	0.9700
20:45629904:AG:A	donor_loss	0.9700
20:45629905:GTAG:G	donor_loss	0.9700
20:45610083:C:CT	donor_gain	0.9600
20:45610113:T:TA	donor_gain	0.9600
20:45631197:TCCTA:T	donor_loss	0.9600
20:45631198:CCTA:C	donor_loss	0.9600
20:45631199:CTAC:C	donor_loss	0.9600
20:45631200:TAC:T	donor_loss	0.9600
20:45629763:G:T	donor_gain	0.9500
20:45629875:G:T	donor_gain	0.9500
20:45608139:CT:C	acceptor_gain	0.9400
20:45629660:G:T	donor_gain	0.9300
20:45630868:A:AG	acceptor_gain	0.9300
20:45630869:G:GG	acceptor_gain	0.9300
20:45610084:C:CT	donor_gain	0.9100
20:45631202:CCT:C	donor_gain	0.9100
20:45610072:C:A	donor_gain	0.9000
20:45629902:AGA:A	donor_gain	0.9000
20:45629903:GAG:G	donor_gain	0.9000
20:45629698:GGCA:G	donor_gain	0.8900
20:45629699:GCAG:G	donor_gain	0.8900
20:45630869:GA:G	acceptor_gain	0.8900

AlphaMissense

589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45608695:C:A	W69C	0.995
20:45608695:C:G	W69C	0.995
20:45608776:C:A	W42C	0.993
20:45608776:C:G	W42C	0.993
20:45608684:C:A	G73V	0.991
20:45608780:C:G	C41S	0.990
20:45608781:A:T	C41S	0.990
20:45608675:C:G	C76S	0.988
20:45608676:A:T	C76S	0.988
20:45608687:C:G	C72S	0.986
20:45608688:A:T	C72S	0.986
20:45608741:C:G	C54S	0.986
20:45608742:A:T	C54S	0.986
20:45608676:A:G	C76R	0.985
20:45608687:C:T	C72Y	0.985
20:45608699:C:G	C68S	0.985
20:45608700:A:T	C68S	0.985
20:45608781:A:G	C41R	0.984
20:45608698:G:C	C68W	0.983
20:45608674:G:C	C76W	0.982
20:45608702:C:T	C67Y	0.982
20:45608779:G:C	C41W	0.982
20:45608675:C:T	C76Y	0.981
20:45608702:C:G	C67S	0.981
20:45608703:A:T	C67S	0.981
20:45608723:C:T	C60Y	0.980
20:45608688:A:G	C72R	0.979
20:45608699:C:T	C68Y	0.979
20:45608700:A:G	C68R	0.979
20:45608701:G:C	C67W	0.978

dbSNP variants (sampled 300 via entrez): RS1000004976 (20:45617776 A>G), RS1000050999 (20:45631896 A>G), RS1000105092 (20:45624351 C>T), RS1000119134 (20:45630272 T>C), RS1000402050 (20:45631554 T>C), RS1000457141 (20:45612877 G>T), RS1000805816 (20:45611207 C>G), RS1001086727 (20:45611536 A>G), RS1001233977 (20:45624593 G>A), RS1001349631 (20:45611641 C>A,T), RS1001361655 (20:45618090 A>G), RS1001408005 (20:45619267 A>G), RS1001571096 (20:45631969 G>A), RS1001774922 (20:45631065 T>A,C), RS1001859162 (20:45618878 T>C,G)

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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1

Clinical trials (associated diseases)

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