WFDC1

protein-coding

WAP four-disulfide core domain 1, the group of WAP four-disulfide core domain containing

Gene summary

This gene encodes a member of the WAP-type four disulfide core domain family. The WAP-type four-disulfide core domain 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 mapped to chromosome 16q24, an area of frequent loss of heterozygosity in cancers, including prostate, breast and hepatocellular cancers and Wilms' tumor. This gene is downregulated in many cancer types and may be involved in the inhibition of cell proliferation. The encoded protein may also play a role in the susceptibility of certain CD4 memory T cells to human immunodeficiency virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_021197.4

Inheritance

—

ClinVar variants

U:62B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.14

Max pathogenic AF

—

Genomic locus

chr16:84,294,846-84,329,844

External References & Databases

Ensembl (ENSG00000103175)

Transcript & Mutation Effects

hg38 • Region Span ~35.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WFDC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021197.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar		3
missense			61 clinvar	2 clinvar	3 clinvar	66
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	5	3	70

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021197.4	RefSeq	NP_067020.2	6	MANE Select
ENST00000219454.10	Ensembl	ENSP00000219454.5	6	MANE Select
NM_001282466.2	RefSeq	NP_001269395.1	6	Standard
NM_001282467.2	RefSeq	NP_001269396.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cell growth
negative regulation of endopeptidase activity
negative regulation of cell growth
response to estradiol
response to drug

Molecular Function

molecular_function
serine-type endopeptidase inhibitor activity

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219454
Coding exons: 6
Length: 35199
Individuals with no LoFs: 125598
Homozygous LoFs: 0
Heterozygous LoFs: 150
Defined: 125748
p: 0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.71	155	105	1.47	0.00000636	1373
Missense (PolyPhen)		42	27.438	1.5307		368
Synonymous	-0.922	56	47.9	1.17	0.00000313	463
Loss of Function	-0.472	15	13.2	1.14	8.12e-7	144

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0042	0.0042	notable
Latino/Admixed American	0.00043	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0014	0.0014	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has growth inhibitory activity. {ECO:0000250}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.815
RVIS EVS: 1.75
RVIS percentile EVS: 96.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.155

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium