WFDC10B

protein-coding

WAP four-disulfide core domain 10B, 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. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Two alternatively spliced transcript variants have been found for this gene, and they encode distinct isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_172006.2

Inheritance

—

ClinVar variants

U:8B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr20:45,684,651-45,705,019

External References & Databases

Ensembl (ENSG00000182931)

Transcript & Mutation Effects

hg38 • Region Span ~20.4 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 WFDC10B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 17

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172006.2. 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			6 clinvar	1 clinvar		7
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	8	1	0	9

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172006.2	RefSeq	NP_742003.1	2	MANE Select
ENST00000330523.10	Ensembl	ENSP00000327628.5	2	MANE Select
NM_172131.2	RefSeq	NP_742143.1	3	Standard
ENST00000335769.2	Ensembl	ENSP00000337466.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of peptidase activity

Molecular Function

peptidase inhibitor activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335769
Coding exons: 3
Length: 20367
Individuals with no LoFs: 124697
Homozygous LoFs: 32
Heterozygous LoFs: 984
Defined: 125713
p: 0.00405

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.162	44	47.1	0.933	0.00000222	587
Missense (PolyPhen)		11	6.3148	1.7419		83
Synonymous	0.913	11	15.6	0.706	6.72e-7	154
Loss of Function	0.377	2	2.66	0.751	1.12e-7	33

Population LoF Frequency

Population	CAF	p-value	Status
African	0.059	0.058	notable
Latino/Admixed American	0.0022	0.0022	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0.00013	0.00013	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.606
RVIS EVS: 0.39
RVIS percentile EVS: 75.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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