WFDC11

Summary

WFDC11 (WAP four-disulfide core domain 11, HGNC:20478) is a protein-coding gene on chromosome 20q13.12, encoding Protein WFDC11 (Q8NEX6).

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 259239 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_147197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20478
Approved symbol	WFDC11
Name	WAP four-disulfide core domain 11
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	WAP11
Ensembl gene	ENSG00000180083
Ensembl biotype	protein_coding
Entrez	259239

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000324384, ENST00000356562, ENST00000618797

RefSeq mRNA: 1 — MANE Select: NM_147197 NM_147197

CCDS: CCDS13364

Canonical transcript exons

ENST00000324384 — 5 exons

Exon	Start	End
ENSE00001266221	45650501	45650651
ENSE00001412524	45670178	45670239
ENSE00001418514	45667088	45667169
ENSE00001419168	45649257	45649399
ENSE00001458286	45648563	45648739

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 85.21.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	85.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.46	gold quality
sperm	CL:0000019	79.44	gold quality
right testis	UBERON:0004534	68.00	gold quality
left testis	UBERON:0004533	67.76	gold quality
testis	UBERON:0000473	65.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.06	gold quality
caput epididymis	UBERON:0004358	52.41	gold quality
cauda epididymis	UBERON:0004360	49.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
lower lobe of lung	UBERON:0008949	43.10	silver quality
body of tongue	UBERON:0011876	42.65	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
subthalamic nucleus	UBERON:0001906	41.40	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
ventral tegmental area	UBERON:0002691	41.13	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
parietal pleura	UBERON:0002400	41.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
tongue	UBERON:0001723	40.75	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	40.58	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting WFDC11, 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-4267	99.96	66.53	2368
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-151A-3P	95.52	65.29	516
HSA-MIR-769-5P	94.45	64.56	603

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc11	ENSMUSG00000078940
rattus_norvegicus	Wfdc11	ENSRNOG00000065546
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), SLPI (ENSG00000124107), WFDC3 (ENSG00000124116), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

Protein WFDC11 — Q8NEX6 (reviewed: Q8NEX6)

All UniProt accessions (1): Q8NEX6

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_671730* (*=MANE)

Domains & families (InterPro)

UniProt features (2 total): signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEX6-F1	77.90	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (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, GOBP_ANTIBACTERIAL_HUMORAL_RESPONSE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, MIR4267, MIR4797_3P

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

GO Molecular Function (1): serine-type endopeptidase inhibitor activity (GO:0004867)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC11	WFDC13	Q8IUB5	719
WFDC11	WFDC10A	Q9H1F0	598
WFDC11	C16orf90	A8MZG2	554
WFDC11	WFDC12	Q8WWY7	544
WFDC11	WFDC8	Q8IUA0	491
WFDC11	WFDC2	Q14508	488
WFDC11	WFDC10B	Q8IUB3	480
WFDC11	IQCF3	P0C7M6	479
WFDC11	SPANXN5	Q5MJ07	476
WFDC11	EDDM3A	Q14507	452
WFDC11	EDDM3B	P56851	443
WFDC11	RGPD4	Q7Z3J3	436
WFDC11	DEFB112	Q30KQ8	434
WFDC11	STARD6	P59095	430
WFDC11	WFDC1	Q9HC57	412

IntAct

3 interactions, top by confidence:

A	B	Type	Score
WFDC11	PLXNA2	psi-mi:“MI:0914”(association)	0.350
WFDC11	ATE1	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): SLC25A14 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), APP (Affinity Capture-MS), GAS6 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCM9 (Affinity Capture-MS), LMLN (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), MROH1 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), CBWD1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

596 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45649256:CGA:C	donor_gain	1.0000
20:45650499:A:AC	donor_gain	1.0000
20:45650500:C:CC	donor_gain	1.0000
20:45650516:T:TA	donor_gain	1.0000
20:45649255:A:AC	donor_gain	0.9900
20:45649256:C:CC	donor_gain	0.9900
20:45650493:C:CT	donor_gain	0.9900
20:45650508:T:C	donor_gain	0.9900
20:45650494:C:CT	donor_gain	0.9800
20:45650500:CTGT:C	donor_gain	0.9800
20:45650666:A:C	acceptor_gain	0.9800
20:45667085:TA:T	donor_loss	0.9800
20:45667087:C:CT	donor_loss	0.9800
20:45649254:CACG:C	donor_gain	0.9700
20:45649255:ACGA:A	donor_gain	0.9700
20:45649256:CGAC:C	donor_gain	0.9700
20:45649256:CG:C	donor_gain	0.9500
20:45650647:CGCTG:C	acceptor_gain	0.9400
20:45650652:C:CC	acceptor_gain	0.9400
20:45650661:A:T	acceptor_gain	0.9400
20:45649256:CGACG:C	donor_gain	0.9300
20:45650771:TGGCA:T	donor_gain	0.9300
20:45650488:C:CA	donor_gain	0.9200
20:45650495:A:T	donor_gain	0.9200
20:45667086:A:AC	donor_gain	0.9200
20:45667087:C:CC	donor_gain	0.9200
20:45650490:TCAC:T	donor_gain	0.9100
20:45650491:CACC:C	donor_gain	0.9100
20:45650492:A:AC	donor_gain	0.9100
20:45650649:CTG:C	acceptor_gain	0.8900

AlphaMissense

580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45649290:C:A	W70C	0.988
20:45649290:C:G	W70C	0.988
20:45649279:C:A	G74V	0.983
20:45649270:C:G	C77S	0.977
20:45649271:A:T	C77S	0.977
20:45649348:C:G	C51S	0.976
20:45649349:A:T	C51S	0.976
20:45649336:C:G	C55S	0.974
20:45649337:A:T	C55S	0.974
20:45649318:C:G	C61S	0.971
20:45649319:A:T	C61S	0.971
20:45649269:G:C	C77W	0.970
20:45649282:C:G	C73S	0.968
20:45649283:A:T	C73S	0.968
20:45649294:C:G	C69S	0.966
20:45649295:A:T	C69S	0.966
20:45649296:G:C	C68W	0.964
20:45649375:C:G	C42S	0.963
20:45649376:A:T	C42S	0.963
20:45649270:C:T	C77Y	0.960
20:45649297:C:G	C68S	0.959
20:45649298:A:T	C68S	0.959
20:45649282:C:T	C73Y	0.957
20:45649293:G:C	C69W	0.957
20:45649271:A:G	C77R	0.952
20:45649349:A:G	C51R	0.952
20:45649297:C:T	C68Y	0.948
20:45649298:A:G	C68R	0.947
20:45649337:A:G	C55R	0.947
20:45649347:A:C	C51W	0.945

dbSNP variants (sampled 300 via entrez): RS1000051994 (20:45648158 G>A), RS1000212113 (20:45664243 C>G), RS1000257159 (20:45659064 A>T), RS1000316312 (20:45651178 C>A), RS1000475569 (20:45654187 C>T), RS1000597623 (20:45660549 A>C,G), RS1000649883 (20:45649750 T>C), RS1000650068 (20:45660714 A>G), RS1000827973 (20:45653938 T>C), RS1000851704 (20:45663206 A>G), RS1000863498 (20:45655881 A>C,G), RS1000884463 (20:45670005 TACAA>T), RS1000918755 (20:45650126 C>T), RS1000953063 (20:45665288 C>T), RS1001014544 (20:45649453 G>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

1 associations (top):

Study	Trait	p-value
GCST007297_14	Psychological distress	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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