WFDC6

Summary

WFDC6 (WAP four-disulfide core domain 6, HGNC:16164) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 6 (Q9BQY6).

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. Read-through transcription exists between this gene and the upstream SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) gene.

Source: NCBI Gene 140870 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_080827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16164
Approved symbol	WFDC6
Name	WAP four-disulfide core domain 6
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ461P17.11, WAP6
Ensembl gene	ENSG00000243543
Ensembl biotype	protein_coding
Entrez	140870

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372670

RefSeq mRNA: 1 — MANE Select: NM_080827 NM_080827

CCDS: CCDS13358

Canonical transcript exons

ENST00000372670 — 3 exons

Exon	Start	End
ENSE00001273600	45539317	45539482
ENSE00001932015	45534196	45534505
ENSE00003660599	45537964	45538094

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 92.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0087 / max 8.1631, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187449	0.0087	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	92.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.41	gold quality
right uterine tube	UBERON:0001302	91.98	gold quality
testis	UBERON:0000473	91.37	gold quality
right testis	UBERON:0004534	91.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.64	gold quality
fallopian tube	UBERON:0003889	65.63	gold quality
right lung	UBERON:0002167	64.93	gold quality
endocervix	UBERON:0000458	55.80	gold quality
left lobe of thyroid gland	UBERON:0001120	53.64	gold quality
endometrium	UBERON:0001295	53.53	gold quality
thyroid gland	UBERON:0002046	52.21	gold quality
right lobe of thyroid gland	UBERON:0001119	48.65	gold quality
left uterine tube	UBERON:0001303	45.99	gold quality
lung	UBERON:0002048	45.08	gold quality
skin of abdomen	UBERON:0001416	43.84	gold quality
upper lobe of left lung	UBERON:0008952	43.81	gold quality
uterine cervix	UBERON:0000002	43.58	gold quality
zone of skin	UBERON:0000014	39.35	gold quality
ganglionic eminence	UBERON:0004023	38.24	gold quality
ectocervix	UBERON:0012249	38.17	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of stomach	UBERON:0001199	36.38	silver quality
skin of leg	UBERON:0001511	36.33	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
omental fat pad	UBERON:0010414	35.67	gold quality
skeletal muscle tissue	UBERON:0001134	35.23	gold quality
vagina	UBERON:0000996	34.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting WFDC6, 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-6077	99.99	68.04	2299
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-378J	96.44	66.20	1020

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	spint1b	ENSDARG00000012467
danio_rerio	lrp11	ENSDARG00000034076
danio_rerio	tfpil	ENSDARG00000089361
danio_rerio	si:dkeyp-73b11.8	ENSDARG00000090185
danio_rerio	wfikkn1	ENSDARG00000101364
danio_rerio	spint1a	ENSDARG00000102332
drosophila_melanogaster	CG7565	FBGN0035833
caenorhabditis_elegans		WBGENE00008304
caenorhabditis_elegans		WBGENE00008449
caenorhabditis_elegans		WBGENE00009386
caenorhabditis_elegans		WBGENE00010792
caenorhabditis_elegans		WBGENE00012186
caenorhabditis_elegans		WBGENE00012814
caenorhabditis_elegans		WBGENE00015355
caenorhabditis_elegans		WBGENE00020648
caenorhabditis_elegans		WBGENE00021939

Paralogs (13): TFPI (ENSG00000003436), EPPIN (ENSG00000101448), TFPI2 (ENSG00000105825), AMBP (ENSG00000106927), LRP11 (ENSG00000120256), WFIKKN1 (ENSG00000127578), KIAA0319 (ENSG00000137261), KIAA0319L (ENSG00000142687), SPINT4 (ENSG00000149651), WFDC8 (ENSG00000158901), SPINT1 (ENSG00000166145), SPINT2 (ENSG00000167642), WFIKKN2 (ENSG00000173714)

Protein

Protein identifiers

WAP four-disulfide core domain protein 6 — Q9BQY6 (reviewed: Q9BQY6)

Alternative names: Putative protease inhibitor WAP6

All UniProt accessions (2): A0A0K0K1K0, Q9BQY6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Ubiquitously expressed, but the highest levels are found in epididymis, testis and trachea.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BQY6-1	1	yes
Q9BQY6-2	2
O95925-3	3

RefSeq proteins (1): NP_543017* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002223	Kunitz_BPTI	Domain
IPR008197	WAP_dom	Domain
IPR036645	Elafin-like_sf	Homologous_superfamily
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR051388	Serpin_venom_toxin	Family

Pfam: PF00014, PF00095

UniProt features (11 total): disulfide bond 5, splice variant 2, domain 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQY6-F1	71.61	0.07

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 (5): 33–61, 48–60, 54–69, 79–127, 102–123

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): TGGNNNNNNKCCAR_UNKNOWN, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, MIR539_3P, MIR485_3P, MIR4709_3P, MIR671_5P, MIR3614_3P, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, TRAVAGLINI_LUNG_CILIATED_CELL

GO Biological Process (0):

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC6	SPINT4	Q6UDR6	810
WFDC6	WFDC8	Q8IUA0	804
WFDC6	WFDC10A	Q9H1F0	586
WFDC6	SCGB1D1	O95968	479
WFDC6	WFDC10B	Q8IUB3	478
WFDC6	WFDC13	Q8IUB5	475
WFDC6	TP53TG5	Q9Y2B4	446
WFDC6	WFDC2	Q14508	430
WFDC6	A0A0G2JH32	A0A0G2JH32	419
WFDC6	ZFP41	Q8N8Y5	419
WFDC6	ZNF540	Q8NDQ6	399
WFDC6	OR51B4	Q9Y5P0	396
WFDC6	KRTAP13-1	Q8IUC0	395
WFDC6	WFDC3	Q8IUB2	394
WFDC6	WFIKKN1	Q96NZ8	390

IntAct

2 interactions, top by confidence:

A	B	Type	Score
WFDC6	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): WFDC6 (Two-hybrid), WFDC6 (Two-hybrid), POMGNT2 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), INHBE (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), MAP7D1 (Affinity Capture-MS), TXNDC16 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

Diamond homologs: A0A6P8HC43, A7X3V7, A8Y7N9, B1B5I8, B2G331, B2ZBB6, B5M0W4, B6ZIW0, C0HJF3, C0HK74, C0HLB2, C0HMC7, C1IBY4, C1IC51, C1IC52, C8YJ94, C8YJ95, D4A2Z2, D8KY58, F5GTK6, F6ULY1, I2G9B4, O35536, O43291, O54819, O76840, O95925, P00976, P00992, P00993, P00994, P0C5J5, P0DJ50, P0DJ66, P0DJ76, P0DL86, P0DMJ1, P0DMJ3, P0DMJ5, P0DMW6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

504 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45539315:A:AC	donor_gain	1.0000
20:45539315:ACTG:A	donor_gain	1.0000
20:45539315:ACTGC:A	donor_gain	1.0000
20:45539316:C:CA	donor_gain	1.0000
20:45539316:CT:C	donor_gain	1.0000
20:45539316:CTG:C	donor_gain	1.0000
20:45539316:CTGC:C	donor_gain	1.0000
20:45539316:CTGCC:C	donor_gain	1.0000
20:45539309:ATACT:A	donor_loss	0.9900
20:45539310:TACTT:T	donor_loss	0.9900
20:45539311:ACT:A	donor_loss	0.9900
20:45539312:CTT:C	donor_loss	0.9900
20:45539313:TTA:T	donor_loss	0.9900
20:45538093:CT:C	acceptor_gain	0.9800
20:45538095:C:CC	acceptor_gain	0.9800
20:45538090:CGGCT:C	acceptor_gain	0.9700
20:45539308:AATAC:A	donor_loss	0.9700
20:45539312:CTTA:C	donor_gain	0.9600
20:45539311:A:AC	donor_gain	0.9300
20:45539312:C:CC	donor_gain	0.9300
20:45537856:ACTCT:A	acceptor_gain	0.9200
20:45537857:CTCTT:C	acceptor_gain	0.9000
20:45538379:AG:A	donor_gain	0.9000
20:45537959:GTTA:G	donor_loss	0.8800
20:45537960:TTA:T	donor_loss	0.8800
20:45537961:TA:T	donor_loss	0.8800
20:45537962:ACC:A	donor_loss	0.8800
20:45537963:CCT:C	donor_loss	0.8800
20:45538094:TCT:T	acceptor_loss	0.8700
20:45538095:CTAAG:C	acceptor_loss	0.8700

AlphaMissense

562 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000272523 (20:45535177 G>A,T), RS1000722292 (20:45535497 T>C), RS1001416692 (20:45541372 A>G), RS1001432665 (20:45535588 C>T), RS1003458473 (20:45538863 TTG>T), RS1003469916 (20:45539280 C>A), RS1003815713 (20:45535660 T>C), RS1003928650 (20:45539604 G>A,T), RS1003937587 (20:45535895 T>C), RS1004649671 (20:45539990 C>T), RS1006090116 (20:45534254 G>T), RS1006144000 (20:45534658 A>G,T), RS1006236472 (20:45536284 C>T), RS1006263220 (20:45541159 A>T), RS1006317891 (20:45541409 A>T)

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
CGP 52608	increases reaction, affects binding	1
Arsenicals	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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