WFDC10A

Summary

WFDC10A (WAP four-disulfide core domain 10A, HGNC:16139) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 10A (Q9H1F0).

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 140832 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_080753

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16139
Approved symbol	WFDC10A
Name	WAP four-disulfide core domain 10A
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ688G8.3, WAP10
Ensembl gene	ENSG00000180305
Ensembl biotype	protein_coding
Entrez	140832

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372643

RefSeq mRNA: 1 — MANE Select: NM_080753 NM_080753

CCDS: CCDS13363

Canonical transcript exons

ENST00000372643 — 2 exons

Exon	Start	End
ENSE00001269286	45630870	45631196
ENSE00001458294	45629739	45629904

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 93.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0947 / max 84.5616, expressed in 18 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184931	0.0689	14
184930	0.0219	3
184932	0.0038	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	93.55	gold quality
cauda epididymis	UBERON:0004360	79.18	gold quality
buccal mucosa cell	CL:0002336	73.46	gold quality
myocardium	UBERON:0002349	73.20	gold quality
oocyte	CL:0000023	73.10	gold quality
parotid gland	UBERON:0001831	71.31	gold quality
tendon of biceps brachii	UBERON:0008188	69.46	gold quality
secondary oocyte	CL:0000655	68.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.00	gold quality
jejunal mucosa	UBERON:0000399	59.72	gold quality
gingival epithelium	UBERON:0001949	59.06	gold quality
heart right ventricle	UBERON:0002080	58.90	gold quality
caput epididymis	UBERON:0004358	58.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	57.77	gold quality
sperm	CL:0000019	54.76	gold quality
medial globus pallidus	UBERON:0002477	54.66	gold quality
endothelial cell	CL:0000115	54.07	gold quality
gingiva	UBERON:0001828	53.74	gold quality
colonic mucosa	UBERON:0000317	53.43	gold quality
esophagus squamous epithelium	UBERON:0006920	53.19	gold quality
jejunum	UBERON:0002115	52.57	gold quality
globus pallidus	UBERON:0001875	51.53	gold quality
seminal vesicle	UBERON:0000998	51.43	gold quality
lower lobe of lung	UBERON:0008949	48.72	silver quality
amniotic fluid	UBERON:0000173	46.91	gold quality
adult organism	UBERON:0007023	46.91	gold quality
skeletal muscle tissue	UBERON:0001134	46.41	gold quality
mammalian vulva	UBERON:0000997	46.10	gold quality
vastus lateralis	UBERON:0001379	45.84	gold quality
quadriceps femoris	UBERON:0001377	45.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting WFDC10A, 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-4677-5P	99.70	70.09	1940
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4296	96.35	63.55	1233

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc10	ENSMUSG00000070529
rattus_norvegicus	Wfdc10a	ENSRNOG00000026067
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), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

WAP four-disulfide core domain protein 10A — Q9H1F0 (reviewed: Q9H1F0)

Alternative names: Putative protease inhibitor WAP10A

All UniProt accessions (1): Q9H1F0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

RefSeq proteins (1): NP_542791* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008197	WAP_dom	Domain
IPR036645	Elafin-like_sf	Homologous_superfamily

Pfam: PF00095

UniProt features (7 total): disulfide bond 4, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1F0-F1	82.91	0.50

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 (4): 41–67, 50–71, 54–66, 60–75

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, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_ANTIBACTERIAL_HUMORAL_RESPONSE, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, HMGA1_TARGET_GENES, SNRNP70_TARGET_GENES

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), 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
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC10A	WFDC9	Q8NEX5	651
WFDC10A	WFDC13	Q8IUB5	637
WFDC10A	WFDC8	Q8IUA0	636
WFDC10A	SPINT4	Q6UDR6	620
WFDC10A	EPPIN	O95925	611
WFDC10A	WFDC3	Q8IUB2	598
WFDC10A	WFDC11	Q8NEX6	598
WFDC10A	WFDC6	Q9BQY6	586
WFDC10A	SPATA25	Q9BR10	541
WFDC10A	WFDC2	Q14508	474
WFDC10A	KCNS1	Q96KK3	450
WFDC10A	SPINT3	P49223	432
WFDC10A	DEFB121	Q5J5C9	431
WFDC10A	GLB1L3	Q8NCI6	379
WFDC10A	DEFB113	Q30KQ7	371

IntAct

3 interactions, top by confidence:

A	B	Type	Score
WFDC10A	ZZEF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (4): ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

153 predictions. Top by Δscore:

Variant	Effect	Δscore
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
20:45629904:AG:A	donor_loss	0.9700
20:45629905:GTAG:G	donor_loss	0.9700
20:45629763:G:T	donor_gain	0.9500
20:45629875:G:T	donor_gain	0.9500
20:45630868:A:AG	acceptor_gain	0.9300
20:45630869:G:GG	acceptor_gain	0.9300
20:45629902:AGA:A	donor_gain	0.9000
20:45629903:GAG:G	donor_gain	0.9000
20:45630869:GA:G	acceptor_gain	0.8900
20:45630869:GAA:G	acceptor_gain	0.8900
20:45629891:G:GT	donor_gain	0.8700
20:45629874:G:GT	donor_gain	0.8500
20:45630869:GAAA:G	acceptor_gain	0.8500
20:45629763:G:GT	donor_gain	0.8400
20:45629912:A:AG	donor_gain	0.8400
20:45629902:AGAGT:A	donor_gain	0.8300
20:45629904:AGT:A	donor_gain	0.8300
20:45630866:TCA:T	acceptor_loss	0.8300
20:45630867:CAGA:C	acceptor_loss	0.8300
20:45630868:A:T	acceptor_loss	0.8300
20:45630869:GAAAC:G	acceptor_gain	0.8300
20:45629903:GAGT:G	donor_gain	0.8200
20:45629906:T:A	donor_gain	0.8200
20:45630867:CAGAA:C	acceptor_gain	0.8200
20:45630868:AGAAA:A	acceptor_gain	0.8200
20:45629905:GT:G	donor_gain	0.8100

AlphaMissense

505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45630956:T:A	C60S	0.979
20:45630957:G:C	C60S	0.979
20:45631001:T:A	C75S	0.972
20:45631002:G:C	C75S	0.972
20:45630938:T:A	C54S	0.968
20:45630939:G:C	C54S	0.968
20:45630974:T:A	C66S	0.963
20:45630975:G:C	C66S	0.963
20:45630926:T:A	C50S	0.961
20:45630927:G:C	C50S	0.961
20:45631002:G:A	C75Y	0.960
20:45630958:T:G	C60W	0.959
20:45631003:C:G	C75W	0.958
20:45630957:G:A	C60Y	0.957
20:45630899:T:A	C41S	0.955
20:45630900:G:C	C41S	0.955
20:45630939:G:A	C54Y	0.953
20:45631001:T:C	C75R	0.953
20:45630977:T:A	C67S	0.952
20:45630978:G:C	C67S	0.952
20:45630956:T:C	C60R	0.951
20:45630989:T:A	C71S	0.951
20:45630990:G:C	C71S	0.951
20:45630993:G:T	G72V	0.951
20:45630974:T:C	C66R	0.943
20:45630975:G:A	C66Y	0.940
20:45630957:G:T	C60F	0.939
20:45630976:C:G	C66W	0.939
20:45631002:G:T	C75F	0.938
20:45630977:T:C	C67R	0.932

dbSNP variants (sampled 300 via entrez): RS1000119134 (20:45630272 T>C), RS1000402050 (20:45631554 T>C), RS1001774922 (20:45631065 T>A,C), RS1002122558 (20:45631273 C>G,T), RS1002405629 (20:45630191 A>G), RS1002510142 (20:45629454 G>T), RS1004129375 (20:45630268 A>G), RS1004288660 (20:45627798 T>G), RS1004568683 (20:45629109 G>A), RS1004919906 (20:45628792 G>C), RS1006193199 (20:45631322 C>T), RS1006478111 (20:45631569 G>A), RS1007026590 (20:45629568 A>G), RS1007358816 (20:45631158 C>A), RS1009937735 (20:45631219 A>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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Estradiol	decreases expression	1
Testosterone	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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