WFDC8

protein-coding

WAP four-disulfide core domain 8, 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 a Kunitz-inhibitor domain, in addition to three WFDC domains. Most WFDC genes 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 the same protein. [provided by RefSeq, Jul 2008]

Previous symbols:

C20orf170

MANE transcript

NM_130896.3

Inheritance

—

ClinVar variants

U:27B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr20:45,551,153-45,579,326

External References & Databases

Ensembl (ENSG00000158901)

Transcript & Mutation Effects

hg38 • Region Span ~28.2 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 WFDC8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 31

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130896.3. 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		1
missense			27 clinvar	3 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	27	4	0	31

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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_130896.3	RefSeq	NP_570966.2	6	MANE Select
ENST00000289953.3	Ensembl	ENSP00000289953.2	6	MANE Select
NM_181510.3	RefSeq	NP_852611.2	6	Standard
ENST00000357199.8	Ensembl	ENSP00000361735.3	6	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: ENST00000357199
Coding exons: 6
Length: 28174
Individuals with no LoFs: 125575
Homozygous LoFs: 1
Heterozygous LoFs: 169
Defined: 125745
p: 0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.676	114	136	0.837	0.00000718	1607
Missense (PolyPhen)		46	49.105	0.93676		611
Synonymous	-0.256	49	46.8	1.05	0.00000236	410
Loss of Function	0.382	13	14.6	0.892	7.99e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00044	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00091	0.00090	rare
South Asian	0.00023	0.00023	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0679

Intolerance Scores

LoFtool: 0.872
RVIS EVS: 0.73
RVIS percentile EVS: 86.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0965

Gene Damage Prediction

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