WFDC2

Summary

WFDC2 (WAP four-disulfide core domain 2, HGNC:15939) is a protein-coding gene on chromosome 20q13.12, encoding WAP four-disulfide core domain protein 2 (Q14508). Broad range protease inhibitor.

This gene encodes a protein that is a member of the 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 in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation.

Source: NCBI Gene 10406 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bronchiectasis and nasal polyposis (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 24 total — 6 pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_006103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15939
Approved symbol	WFDC2
Name	WAP four-disulfide core domain 2
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	HE4, WAP5, dJ461P17.6, EDDM4
Ensembl gene	ENSG00000101443
Ensembl biotype	protein_coding
OMIM	617548
Entrez	10406

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000217425, ENST00000339946, ENST00000342873, ENST00000372676, ENST00000447118, ENST00000462062, ENST00000488143, ENST00000938555, ENST00000938556, ENST00000938557, ENST00000938558, ENST00000938559

RefSeq mRNA: 1 — MANE Select: NM_006103 NM_006103

CCDS: CCDS35501

Canonical transcript exons

ENST00000372676 — 4 exons

Exon	Start	End
ENSE00001280384	45470389	45470532
ENSE00001820997	45481371	45481532
ENSE00001890832	45469753	45469860
ENSE00003617090	45479942	45480094

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 99.91.

FANTOM5 (CAGE): breadth broad, TPM avg 40.5291 / max 5307.7169, expressed in 663 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184922	36.0917	601
184921	3.7338	432
184923	0.2676	67
184924	0.2275	33
184926	0.1183	50
184927	0.0495	18
184925	0.0406	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.91	gold quality
nasal cavity epithelium	UBERON:0005384	99.87	gold quality
right uterine tube	UBERON:0001302	99.80	gold quality
nasal cavity mucosa	UBERON:0001826	99.80	gold quality
epithelium of bronchus	UBERON:0002031	99.64	gold quality
bronchial epithelial cell	CL:0002328	99.63	gold quality
bronchus	UBERON:0002185	99.56	gold quality
metanephros cortex	UBERON:0010533	99.52	gold quality
right lobe of thyroid gland	UBERON:0001119	99.14	gold quality
left lobe of thyroid gland	UBERON:0001120	99.12	gold quality
palpebral conjunctiva	UBERON:0001812	98.68	gold quality
thyroid gland	UBERON:0002046	98.54	gold quality
corpus epididymis	UBERON:0004359	98.33	gold quality
trachea	UBERON:0003126	98.28	gold quality
rectum	UBERON:0001052	98.04	gold quality
gall bladder	UBERON:0002110	98.03	gold quality
seminal vesicle	UBERON:0000998	97.81	gold quality
cauda epididymis	UBERON:0004360	97.80	gold quality
saliva-secreting gland	UBERON:0001044	97.50	gold quality
parotid gland	UBERON:0001831	97.45	gold quality
minor salivary gland	UBERON:0001830	97.38	gold quality
adenohypophysis	UBERON:0002196	97.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.21	gold quality
caput epididymis	UBERON:0004358	96.99	gold quality
upper lobe of left lung	UBERON:0008952	96.78	gold quality
sigmoid colon	UBERON:0001159	96.71	gold quality
pituitary gland	UBERON:0000007	96.64	gold quality
mucosa of transverse colon	UBERON:0004991	96.50	gold quality
right lung	UBERON:0002167	96.31	gold quality
upper lobe of lung	UBERON:0008948	96.29	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 31.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	30672.85
E-CURD-114	yes	18022.47
E-HCAD-15	yes	14790.21
E-HCAD-1	yes	11891.48
E-MTAB-10287	yes	10738.89
E-MTAB-6653	yes	7024.44
E-MTAB-8221	yes	4427.26
E-MTAB-6308	yes	3779.07
E-CURD-126	yes	3498.03
E-MTAB-8530	yes	3437.35
E-MTAB-10662	yes	3145.09
E-MTAB-9841	yes	3095.29
E-MTAB-10855	yes	2867.99
E-GEOD-124472	yes	2421.11
E-GEOD-125970	yes	2360.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, NFIB

miRNA regulators (miRDB)

13 targeting WFDC2, 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-4492	99.87	68.25	3611
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004

Literature-anchored findings (GeneRIF, showing 40)

• This protein’s gene is amplified in ovarian carcinoma; it can serve as a tumor marker for this disease. (PMID:12839961)
• HE4 is a secreted glycoprotein that is overexpressed by serous and endometrioid endometrioid ovarian carcinoma. (PMID:15781627)
• WFDC2 may be a component of the innate immune defences of the lung, nasal and oral cavities that functions in concert with related WAP domain-containing proteins in epithelial host defence. (PMID:16600032)
• WFDC2 is upregulated after radical prostatectomy for prostatic neoplasms. (PMID:17448597)
• Assays measuring HE4 in serum and other bodily fluids are likely to be clinically useful for patients with ovarian cancer. (PMID:18546615)
• Measuring HE4 serum concentrations increases the accuracy of ovarian cancer diagnosis and provides valuable information to discriminate ovarian tumours from ovarian endometriotic cysts. (PMID:19337252)
• HE4 may have more potential than cancer antigen 125 in discriminating benign from cancerous ovarian masses, and has the strongest correlation with endometrial cancer of all markers tested to date. [REVIEW] (PMID:19732003)
• The median CA125 and HE4 serum levels were significantly higher among ovarian cancer patients as compared with healthy subjects and with those with benign mass, cervical, and endometrial tumor (PMID:19774626)
• The HE4 level was significantly increased in patients with transitional cell carcinoma compared to patients with benign urinary diseases patients (P<0.01) and healthy controls. (PMID:19927341)
• Measuring HE4 in urine may aid diagnosis and the monitoring of response to the response to therapy in ovarian neoplasms. (PMID:20381233)
• a statistically significant difference in serum HE4 levels was observed during the different hormonal phases in the group of women under 35 years. (PMID:20490961)
• Elevated levels of HE4 is associated with ovarian carcinoma in patients with pelvic masses. (PMID:20593939)
• High HE4 expression is associated with lymph node metastases in breast cancer. (PMID:21115941)
• Human epididymis protein 4 used in conjunction with CA 125 yields improved specificity for ovarian cancer compared with the use of CA 125 alone. (PMID:21633297)
• may be a useful marker preoperatively in the clinical decision process for determining the need for lymph node dissection in women with endometrioid endometrial cancer (PMID:21720250)
• increasing levels of serum HE4 was significantly associated with worse progression-free survival and overall survival in ovarian cancer patients (PMID:21738039)
• High serum HE4 levels significantly correlated with high tumor grade and serous histology in epithelial ovarian cancer. In addition, high serum HE4 levels were significantly associated with residual tumor size and operative time (PMID:21833668)
• HE4 alone and even more the combined analysis of CA125 and HE4 using risk of malignancy algorithm improve the diagnostic accuracy of adnexal masses, especially in early ovarian cancer. (PMID:21923475)
• These data showed that high-level HE4-V3 expression is associated with a favorable prognosis in lung adenocarcinoma. (PMID:22015929)
• HE4 is elevated in a high proportion of endometrial cancer patients. (PMID:22037318)
• HE4 levels in healthy subjects are associated with age and smoking status (PMID:22105734)
• This is the first report to demonstrate the functional importance of HE4 in multiple cellular processes and indicates that HE4 may play a protective role in the progression of ovarian cancer (PMID:22117965)
• Serum HE4 levels were elevated less frequently than CA125 levels in benign disease, particularly in premenopausal patients. (PMID:22284961)
• Above the age of 40 years significant elevations in HE4 concentrations emerged with advancing age. In pregnant women, median HE4 concentrations were significantly lower than their premenopausal counterparts. (PMID:22301440)
• these results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in epithelial ovarian cancer progression. (PMID:22342977)
• Findings suggest that serum epididymis protein 4 (HE4) is a potential diagnostic and prognostic marker for lung cancer. (PMID:22373583)
• adds valuable information to CA125 in identifying patients with epithelial ovarian cancer from those with benign pelvic disease (PMID:22426406)
• HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma. (PMID:22430259)
• HE4 is vastly more specific and early-phase diagnosed tumor marker in cases with ovarian cancer. (PMID:22524132)
• Pretherapeutic serum HE4 levels alone and in combination with CA125 are an independent prognostic marker in endometrial cancer patients. (PMID:22525819)
• The current study reports a novel finding of increased serum and pleural fluid HE4 levels in patients with malignant effusions compared to non-malignant effusions. (PMID:22684816)
• This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer. (PMID:22745553)
• High serum HE4 is associated with recurrence of ovarian cancer. (PMID:22875782)
• Because of the strong effect of age on HE4, thresholds for HE4 are best defined for women of specific ages. (PMID:22962406)
• results show that preoperative plasma level of HE4 is a marker of ovarian cancer aggressiveness and a predictor of death (PMID:22967799)
• Determination of HE4 along with CA125 and ROMA2 index calculation is a suitable method for the improvement of the primary detection of ovarian cancer. (PMID:22993374)
• High serum HE4 level is associated with pulmonary adenocarcinoma progression. (PMID:23001907)
• study demonstrated that up-regulation of the extracellular protease inhibitor HE4 is associated with carcinogenesis in the stomach and pancreas (PMID:23084584)
• HE4 has the highest relevance in ovarian cancer but can be elevated in a variety of benign and malignant diseases (PMID:23093276)
• present consensus statements on the different topics, where available,and suggestions for further studies and evaluations required to establish optimal use of HE4, for diagnostic and prognostic purposes in gynecological malignancies (PMID:23093277)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wfdc2	ENSMUSG00000017723
rattus_norvegicus	Wfdc2	ENSRNOG00000014739

Protein

Protein identifiers

WAP four-disulfide core domain protein 2 — Q14508 (reviewed: Q14508)

Alternative names: Epididymal secretory protein E4, Major epididymis-specific protein E4, Putative protease inhibitor WAP5

All UniProt accessions (3): Q14508, A0A384MTN6, A8K2M3

UniProt curated annotations — full annotation on UniProt →

Function. Broad range protease inhibitor.

Subunit / interactions. Homotrimer; disulfide-linked.

Subcellular location. Secreted.

Tissue specificity. Expressed in a number of normal tissues, including male reproductive system, regions of the respiratory tract and nasopharynx. Highly expressed in a number of tumors cells lines, such ovarian, colon, breast, lung and renal cells lines. Initially described as being exclusively transcribed in the epididymis.

Disease relevance. Bronchiectasis and nasal polyposis (BENP) [MIM:620984] An autosomal recessive destructive airway disease characterized by persistent abnormal dilatation of the bronchi, and severe chronic rhinosinusitis with nasal polyposis. Affected individuals suffer from sub-normal lung function, chronic productive cough, excessive sputum production, and recurrent sinopulmonary infections. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q14508-1	1	yes
Q14508-2	2, HE4-V3
Q14508-3	3, HE4-V2
Q14508-4	4, HE4-V1
Q14508-5	5, HE4-V4

RefSeq proteins (1): NP_006094* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008197	WAP_dom	Domain
IPR036645	Elafin-like_sf	Homologous_superfamily
IPR050514	WAP_four-disulfide_core	Family

Pfam: PF00095

UniProt features (26 total): disulfide bond 8, splice variant 7, sequence variant 4, domain 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14508-F1	82.18	0.46

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 (8): 93–114, 97–109, 103–119, 36–62, 45–66, 49–61, 55–70, 80–110

Glycosylation sites (1): 44

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 194 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MODULE_172, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_MALE_GAMETE_GENERATION, CHANDRAN_METASTASIS_DN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, MODULE_66, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SMID_BREAST_CANCER_LUMINAL_B_UP

GO Biological Process (4): proteolysis (GO:0006508), spermatogenesis (GO:0007283), antibacterial humoral response (GO:0019731), innate immune response (GO:0045087)

GO Molecular Function (6): endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), cysteine-type endopeptidase inhibitor activity (GO:0004869), aspartic-type endopeptidase inhibitor activity (GO:0019828), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endopeptidase inhibitor activity	3
protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
antimicrobial humoral response	1
defense response to bacterium	1
immune response	1
defense response to symbiont	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
serine-type endopeptidase activity	1
cysteine-type endopeptidase activity	1
aspartic-type endopeptidase activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WFDC2	PRSS35	Q8N3Z0	605
WFDC2	SLPI	P03973	601
WFDC2	AGR2	O95994	591
WFDC2	MUC16	Q8WXI7	580
WFDC2	CEACAM5	P06731	568
WFDC2	PRSS23	O95084	547
WFDC2	WFDC13	Q8IUB5	523
WFDC2	CHI3L1	P30923	506
WFDC2	MSLN	Q13421	505
WFDC2	PEBP4	Q96S96	501
WFDC2	MMP2	P08253	499
WFDC2	WFDC9	Q8NEX5	498
WFDC2	MMP9	P14780	492
WFDC2	WFDC11	Q8NEX6	488
WFDC2	IGF1R	P08069	482

IntAct

81 interactions, top by confidence:

A	B	Type	Score
WFDC2	ANXA2	psi-mi:“MI:0914”(association)	0.740
WFDC2	ANXA2	psi-mi:“MI:0915”(physical association)	0.740
WFDC2	ANXA2	psi-mi:“MI:0403”(colocalization)	0.740
WFDC2	ANXA2	psi-mi:“MI:0407”(direct interaction)	0.740
WFDC2	FKBP7	psi-mi:“MI:0915”(physical association)	0.670
STOM	WFDC2	psi-mi:“MI:0915”(physical association)	0.560
CD79A	WFDC2	psi-mi:“MI:0915”(physical association)	0.560
WFDC2	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
WFDC2	FAM209A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (32): WDR81 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), CRTAC1 (Affinity Capture-MS), PTPRF (Affinity Capture-MS), EMC4 (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), GRN (Affinity Capture-MS), FKBP7 (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), WFDC2 (Two-hybrid), WFDC2 (Two-hybrid), PTN (Two-hybrid), WFDC2 (Two-hybrid), WFDC2 (Two-hybrid)

ESM2 similar proteins: A4K2M5, A4K2N9, A4K2P7, A4K2Q7, A4K2R4, A4K2S3, A4K2T2, A4K2U0, A4K2V3, A4K2W7, A4K2X5, A4K2Y3, A7X4K1, A7X4M7, B5G6G7, B5G6G8, B5G6G9, B5G6H0, B5G6H1, B5G6H2, B5G6H3, B5G6H4, B5G6H5, B5KGY9, B5L5M9, B5L5N1, B5L5N2, B5L5N3, B5L5N4, B5L5N6, B5L5P0, B5L5P2, B5L5P3, B5L5P4, B5L5P5, B5L5P6, B5L5P7, B5L5P8, B5L5P9, O46655

Diamond homologs: A7X4I7, A7X4J4, A7X4K1, A7X4K7, A7X4L4, P33005, P60589, Q14508, Q28631, Q28894, Q8CHN3, Q8MI69, Q90369, Q9DAU7, Q9N0L8, Q868Z9, P86730, A4K2S3, P01174, P22298, P23352, P62810, P62811, A4K2Y4, B5G6H1, B5G6H2, B5G6H3, B5G6H4, B5G6H5, B5KGY9, B5L5N1, B5L5N3, B5L5N4, B5L5N6, B5L5P0, B5L5P2, B5L5P6, B5L5P7, P00993, Q6V9X0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	15
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3363111	C49R	Pathogenic
3363112	C103R	Pathogenic
3363113	G91S	Pathogenic
3363114	WFDC2, EX1-2 DEL	Pathogenic
4072247	NM_006103.4(WFDC2):c.291C>G (p.Cys97Trp)	Pathogenic
4839417	NM_006103.4(WFDC2):c.24dup (p.Leu9fs)	Pathogenic

SpliceAI

829 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45469859:AGGT:A	donor_loss	1.0000
20:45479940:A:AG	acceptor_gain	1.0000
20:45479941:G:GG	acceptor_gain	1.0000
20:45469861:G:GG	donor_gain	0.9900
20:45471247:GAT:G	donor_gain	0.9900
20:45479937:CCCA:C	acceptor_loss	0.9900
20:45479939:CA:C	acceptor_loss	0.9900
20:45479941:G:GA	acceptor_loss	0.9900
20:45480091:TGAGG:T	donor_loss	0.9900
20:45480092:GAG:G	donor_gain	0.9900
20:45480093:AGGT:A	donor_loss	0.9900
20:45480095:G:GA	donor_loss	0.9900
20:45480096:TAAG:T	donor_loss	0.9900
20:45481369:A:AG	acceptor_gain	0.9900
20:45481370:G:GG	acceptor_gain	0.9900
20:45469857:TCAG:T	donor_gain	0.9800
20:45469858:CAG:C	donor_gain	0.9800
20:45469862:T:G	donor_loss	0.9800
20:45479937:C:G	acceptor_gain	0.9800
20:45479941:GAT:G	acceptor_gain	0.9800
20:45479941:GATA:G	acceptor_gain	0.9800
20:45479941:GATAA:G	acceptor_gain	0.9800
20:45481366:TCCA:T	acceptor_loss	0.9800
20:45481367:CCA:C	acceptor_loss	0.9800
20:45481368:CA:C	acceptor_loss	0.9800
20:45481369:A:C	acceptor_loss	0.9800
20:45481370:G:C	acceptor_loss	0.9800
20:45469859:AG:A	donor_gain	0.9700
20:45469860:GG:G	donor_gain	0.9700
20:45480095:G:GG	donor_gain	0.9700

AlphaMissense

810 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45479950:G:T	G78C	0.996
20:45480007:T:A	C97S	0.996
20:45480008:G:C	C97S	0.996
20:45480025:T:A	C103S	0.995
20:45480026:G:C	C103S	0.995
20:45480016:G:C	D100H	0.993
20:45480042:A:C	K108N	0.993
20:45480042:A:T	K108N	0.993
20:45480043:T:A	C109S	0.993
20:45480044:G:C	C109S	0.993
20:45479995:T:A	C93S	0.991
20:45479996:G:C	C93S	0.991
20:45480017:A:T	D100V	0.991
20:45470489:G:C	K60N	0.990
20:45470489:G:T	K60N	0.990
20:45479956:T:A	C80S	0.989
20:45479957:G:C	C80S	0.989
20:45480058:T:A	C114S	0.989
20:45480059:G:C	C114S	0.989
20:45480025:T:C	C103R	0.988
20:45480007:T:C	C97R	0.987
20:45480073:T:A	C119S	0.986
20:45480074:G:C	C119S	0.986
20:45480054:T:A	N112K	0.985
20:45480054:T:G	N112K	0.985
20:45480055:G:T	G113C	0.985
20:45470472:T:A	C55S	0.983
20:45470473:G:C	C55S	0.983
20:45470490:T:A	C61S	0.983
20:45470491:G:C	C61S	0.983

dbSNP variants (sampled 300 via entrez): RS1000129523 (20:45468353 A>C,G), RS1000800696 (20:45474918 T>C), RS1000810823 (20:45481176 A>C,G), RS1000837134 (20:45481573 G>A), RS1000905424 (20:45478939 A>G), RS1000916770 (20:45479422 C>A,T), RS1001141529 (20:45468284 G>A,C), RS1001323844 (20:45474725 G>A), RS1001374661 (20:45473237 T>C), RS1001696148 (20:45480189 G>A), RS1001725413 (20:45468680 C>A,T), RS1002154548 (20:45475328 T>A), RS1002184333 (20:45475683 C>G,T), RS1002239372 (20:45473847 C>G,T), RS1002296817 (20:45469172 A>C,G)

Disease associations

OMIM: gene MIM:617548 | disease phenotypes: MIM:620984

GenCC curated gene-disease

Disease	Classification	Inheritance
bronchiectasis and nasal polyposis	Strong	Autosomal recessive

Mondo (1): bronchiectasis and nasal polyposis (MONDO:0975835)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0002110	Bronchiectasis
HP:0002643	Neonatal respiratory distress
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0011109	Chronic sinusitis
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011534	Abnormal spatial orientation of the cardiac segments
HP:0012735	Cough
HP:0032342	Reduced forced expiratory volume in one second
HP:0033036	Decreased nasal nitric oxide
HP:0100582	Nasal polyposis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000597_8	Brain structure	9.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects expression, increases expression	3
Smoke	increases abundance, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects expression, affects response to substance	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	increases expression, decreases expression	2
uranyl acetate	affects expression	1
terbufos	increases methylation	1
cobaltous chloride	increases expression	1
tanshinone	increases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases expression	1
Resveratrol	increases expression	1
Decitabine	affects expression	1
Arsenic	affects methylation	1
Asbestos	affects expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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