WFDC3

protein-coding

WAP four-disulfide core domain 3, the group of WAP four-disulfide core domain containing

Gene summary

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. The encoded protein contains four WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Alternatively spliced transcript variants have been observed but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_080614.2

Inheritance

—

ClinVar variants

U:46

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr20:45,747,944-45,791,932

External References & Databases

Ensembl (ENSG00000124116)

Transcript & Mutation Effects

hg38 • Region Span ~44.0 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 WFDC3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 44

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080614.2. 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						0
missense			45 clinvar			45
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	0	0	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080614.2	RefSeq	NP_542181.1	6	MANE Select
ENST00000243938.9	Ensembl	ENSP00000243938.4	6	MANE Select
ENST00000337205.8	Ensembl	ENSP00000337815.4	7	Standard
ENST00000372630.2	Ensembl	ENSP00000361713.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243938
Coding exons: 6
Length: 43989
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.405	119	132	0.901	0.00000710	1495
Missense (PolyPhen)		40	47.889	0.83527		535
Synonymous	-0.0866	50	49.2	1.02	0.00000270	439
Loss of Function	0.0977	11	11.4	0.969	5.60e-7	146

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0908

Intolerance Scores

LoFtool: 0.476
RVIS EVS: 0.95
RVIS percentile EVS: 90.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.337

Gene Damage Prediction

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