WFDC10B

Summary

WFDC10B (WAP four-disulfide core domain 10B, HGNC:20479) is a protein-coding gene on chromosome 20q13.12, encoding Protein WFDC10B (Q8IUB3).

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. Two alternatively spliced transcript variants have been found for this gene, and they encode distinct isoforms.

Source: NCBI Gene 280664 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_172006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20479
Approved symbol	WFDC10B
Name	WAP four-disulfide core domain 10B
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	WAP12
Ensembl gene	ENSG00000182931
Ensembl biotype	protein_coding
Entrez	280664

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000330523, ENST00000335769, ENST00000937249

RefSeq mRNA: 2 — MANE Select: NM_172006 NM_172006, NM_172131

CCDS: CCDS13365, CCDS13366

Canonical transcript exons

ENST00000330523 — 4 exons

Exon	Start	End
ENSE00001309290	45685902	45686056
ENSE00003621896	45704918	45705019
ENSE00003629256	45704497	45704561
ENSE00003930807	45684651	45684960

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 87.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0464 / max 20.0146, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187471	0.0464	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.81	gold quality
cauda epididymis	UBERON:0004360	70.67	gold quality
lower esophagus mucosa	UBERON:0035834	70.02	gold quality
right testis	UBERON:0004534	68.61	gold quality
corpus epididymis	UBERON:0004359	67.41	gold quality
left testis	UBERON:0004533	66.91	gold quality
skin of leg	UBERON:0001511	64.98	gold quality
testis	UBERON:0000473	64.52	gold quality
skin of abdomen	UBERON:0001416	61.92	gold quality
zone of skin	UBERON:0000014	60.59	gold quality
upper lobe of left lung	UBERON:0008952	60.31	gold quality
upper lobe of lung	UBERON:0008948	58.37	gold quality
caput epididymis	UBERON:0004358	57.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	55.15	gold quality
lower esophagus	UBERON:0013473	54.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	54.84	gold quality
mucosa of stomach	UBERON:0001199	54.35	gold quality
smooth muscle tissue	UBERON:0001135	53.89	gold quality
right lung	UBERON:0002167	53.71	gold quality
fundus of stomach	UBERON:0001160	53.69	gold quality
urinary bladder	UBERON:0001255	53.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	52.88	gold quality
transverse colon	UBERON:0001157	51.96	gold quality
apex of heart	UBERON:0002098	51.83	gold quality
left coronary artery	UBERON:0001626	51.65	gold quality
coronary artery	UBERON:0001621	50.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	50.04	gold quality
rectum	UBERON:0001052	49.64	gold quality
tibial artery	UBERON:0007610	49.34	gold quality
popliteal artery	UBERON:0002250	49.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting WFDC10B, 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-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-105-3P	89.64	64.48	52

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC3 (ENSG00000124116), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC11 (ENSG00000180083), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305)

Protein

Protein identifiers

Protein WFDC10B — Q8IUB3 (reviewed: Q8IUB3)

All UniProt accessions (1): Q8IUB3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Ubiquitously expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IUB3-1	1, WAP12a	yes
Q8IUB3-2	2, WAP12b

RefSeq proteins (2): NP_742003, NP_742143 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008197	WAP_dom	Domain

UniProt features (5 total): signal peptide 1, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUB3-F1	86.02	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_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, LHX9_TARGET_GENES, MIR4441, MIR4270

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

212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC10B	WFDC3	Q8IUB2	657
WFDC10B	SPINT4	Q6UDR6	642
WFDC10B	WFDC13	Q8IUB5	583
WFDC10B	ZSWIM1	Q9BR11	580
WFDC10B	SPATA25	Q9BR10	575
WFDC10B	SNX21	Q969T3	526
WFDC10B	C6orf163	Q5TEZ5	518
WFDC10B	CFAP107	Q8N1D5	507
WFDC10B	WFDC11	Q8NEX6	480
WFDC10B	NEURL2	Q9BR09	480
WFDC10B	WFDC6	Q9BQY6	478
WFDC10B	FAM181B	A6NEQ2	471
WFDC10B	ZNF335	Q9H4Z2	464
WFDC10B	SYS1	Q8N2H4	447
WFDC10B	DNTTIP1	Q9H147	403

IntAct

7 interactions, top by confidence:

A	B	Type	Score
	WFDC10B	psi-mi:“MI:0915”(physical association)	0.560
WFDC10B		psi-mi:“MI:0915”(physical association)	0.560
WFDC10B	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
WFDC10B	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): KRTAP10-3 (Two-hybrid), UBQLN2 (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: A2A5H7, Q3UW41, Q6IE41, Q8IUB3, Q8NEX5, Q8NEX6, Q9H1F0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

789 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45702212:G:GG	donor_gain	1.0000
20:45685901:CT:C	donor_gain	0.9900
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
20:45702155: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
20:45685900:A:AC	donor_gain	0.9700
20:45685901:C:CC	donor_gain	0.9700
20:45704442:A:AG	acceptor_gain	0.9700
20:45704443:G:GG	acceptor_gain	0.9700
20:45704958:CA:C	donor_gain	0.9700
20:45702205: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
20:45702208:CTGA:C	donor_loss	0.9400
20:45702209:TGAG:T	donor_loss	0.9400
20:45702211:AG:A	donor_loss	0.9400
20:45702212:GTAG:G	donor_loss	0.9400

AlphaMissense

473 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45684858:C:G	C65S	0.915
20:45684859:A:T	C65S	0.915
20:45684846:C:G	C69S	0.913
20:45684847:A:T	C69S	0.913
20:45684909:C:G	C48S	0.910
20:45684910:A:T	C48S	0.910
20:45684921:C:G	C44S	0.907
20:45684922:A:T	C44S	0.907
20:45684855:C:A	G66V	0.902
20:45684845:A:C	C69W	0.900
20:45684891:C:G	C54S	0.891
20:45684892:A:T	C54S	0.891
20:45684899:G:C	F51L	0.889
20:45684899:G:T	F51L	0.889
20:45684901:A:G	F51L	0.889
20:45684858:C:T	C65Y	0.886
20:45684873:C:G	C60S	0.878
20:45684874:A:T	C60S	0.878
20:45684908:A:C	C48W	0.877
20:45684846:C:T	C69Y	0.876
20:45684859:A:G	C65R	0.876
20:45684900:A:C	F51C	0.859
20:45684860:G:C	F64L	0.851
20:45684860:G:T	F64L	0.851
20:45684862:A:G	F64L	0.851
20:45684892:A:G	C54R	0.849
20:45684847:A:G	C69R	0.847
20:45684909:C:T	C48Y	0.845
20:45684920:G:C	C44W	0.843
20:45684870:C:G	C61S	0.842

dbSNP variants (sampled 300 via entrez): RS1000127693 (20:45685887 C>A,G,T), RS1000182242 (20:45693100 C>A,G,T), RS1000324820 (20:45694940 G>A), RS1000336479 (20:45698785 G>A), RS1000418716 (20:45687983 C>T), RS1000508567 (20:45691942 T>G), RS1000685066 (20:45699095 G>A), RS1000818625 (20:45703851 T>G), RS1000864432 (20:45699981 A>C), RS1001056750 (20:45700836 A>C,G), RS1001666548 (20:45693531 G>A,T), RS1001861492 (20:45687182 TG>T), RS1001916107 (20:45688387 C>T), RS1001959132 (20:45685122 A>T), RS1001960808 (20:45692592 C>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
Benzo(a)pyrene	increases expression, affects methylation	2
sotorasib	decreases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Folic Acid	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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