KLK14

protein-coding

kallikrein related peptidase 14, the group of Kallikreins

Gene summary

This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The altered expression of this gene is implicated in the progression of different cancers including breast and prostate tumors. The encoded protein is a precursor that is proteolytically processed to generate the functional enzyme. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

MANE transcript

NM_001369775.2

Inheritance

—

ClinVar variants

U:33B:3

Top phenotype

Male infertility

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr19:51,077,495-51,084,245

External References & Databases

Ensembl (ENSG00000129437)

Transcript & Mutation Effects

hg38 • Region Span ~6.8 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 KLK14 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 4

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001369775.2. 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			1 clinvar			1
missense			31 clinvar	2 clinvar		33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	0	0	33	3	0	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001369775.2	RefSeq	NP_001356704.1	5	MANE Select
ENST00000650543.2	Ensembl	ENSP00000497141.1	5	MANE Select
NM_001311182.2	RefSeq	NP_001298111.2	5	Standard
NM_022046.6	RefSeq	NP_071329.3	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

proteolysis
fertilization
negative regulation of G protein-coupled receptor signaling pathway
positive regulation of G protein-coupled receptor signaling pathway
epidermis morphogenesis

Molecular Function

serine-type endopeptidase activity

Cellular Component

extracellular region
extracellular space
secretory granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000391802
Coding exons: 6
Length: 6751
Individuals with no LoFs: 121314
Homozygous LoFs: 55
Heterozygous LoFs: 3428
Defined: 124797
p: 0.0141

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.385	150	164	0.915	0.0000101	1681
Missense (PolyPhen)		51	56.105	0.909		626
Synonymous	1.22	58	71.1	0.816	0.00000483	554
Loss of Function	0.0801	12	12.3	0.975	6.81e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0049	0.0049	notable
Latino/Admixed American	0.0092	0.0091	notable
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.00011	0.00011	rare
Finnish	0.0080	0.0080	notable
European (Non-Finnish)	0.016	0.016	notable
South Asian	0.033	0.033	notable
Other	0.011	0.011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine-type endopeptidase with a dual trypsin-like and chymotrypsin-like substrate specificity. May activate/inactivate the proteinase-activated receptors F2R, F2RL1 and F2RL3 and other kallikreins including KLK1, KLK3, KLK5 and KLK11. May function in seminal clot liquefaction through direct cleavage of the semenogelin SEMG1 and SEMG2 and activation of KLK3. May function through desmoglein DSG1 cleavage in epidermal desquamation a process by which the most superficial corneocytes are shed from the skin surface. May be involved in several aspects of tumor progression including growth, invasion and angiogenesis. {ECO:0000269|PubMed:15654974, ECO:0000269|PubMed:16885167, ECO:0000269|PubMed:17158887, ECO:0000269|PubMed:17625593, ECO:0000269|PubMed:18056261, ECO:0000269|PubMed:18482984}.;

Intolerance Scores

LoFtool: 0.343
RVIS EVS: 2.64
RVIS percentile EVS: 98.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0664

Gene Damage Prediction

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