KLK4

kallikrein related peptidase 4, the group of Kallikreins|Serine proteases

Basic information

Region (hg38): 19:50906351-50911395

Previous symbols: [ "PRSS17" ]

Links

ENSG00000167749 ∙ NCBI:9622 ∙ OMIM:603767 ∙ HGNC:6365 ∙ Uniprot:Q9Y5K2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amelogenesis imperfecta type 2A1 (Moderate), mode of inheritance: AR
• amelogenesis imperfecta type 2A1 (Strong), mode of inheritance: AR
• amelogenesis imperfecta type 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type IIA1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental	15235027; 23355523

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLK4 gene.

• not provided (1 variants)
• Amelogenesis imperfecta type 2A1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLK4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	3	5
missense			13		2	15
nonsense		1				1
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding		1			16	17
Total	1	3	13	2	21

Highest pathogenic variant AF is 0.0000525

Variants in KLK4

This is a list of pathogenic ClinVar variants found in the KLK4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-50906915-G-A		not specified	Benign (Jun 19, 2021)
19-50906943-C-T		KLK4-related disorder	Likely benign (Oct 01, 2022)
19-50906958-T-C		Inborn genetic diseases	Uncertain significance (Sep 24, 2024)
19-50907002-C-T		Inborn genetic diseases • KLK4-related disorder	Uncertain significance (Feb 13, 2018)
19-50907019-G-A		Inborn genetic diseases • Male infertility	Uncertain significance (Feb 13, 2018)
19-50907058-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
19-50907062-A-G		Amelogenesis imperfecta	Pathogenic (-)
19-50907066-CA-C		Amelogenesis imperfecta type 2A1	Pathogenic (May 24, 2016)
19-50907077-CAG-C		Amelogenesis imperfecta type 2A1	Likely pathogenic (Aug 23, 2021)
19-50907142-G-A			Benign (Jun 20, 2021)
19-50907215-A-G			Benign (Nov 12, 2018)
19-50908073-G-A			Benign (Jun 19, 2021)
19-50908132-T-C			Benign (Jun 19, 2021)
19-50908309-C-T			Benign (Jun 20, 2021)
19-50908375-T-G		Inborn genetic diseases	Uncertain significance (Oct 09, 2024)
19-50908380-T-T		not specified	Benign (Nov 12, 2018)
19-50908388-C-G		Inborn genetic diseases	Uncertain significance (Sep 09, 2024)
19-50908390-C-T		Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
19-50908426-T-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
19-50908465-T-C		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
19-50908486-G-A		Inborn genetic diseases	Uncertain significance (Aug 06, 2021)
19-50908495-C-T			Benign (Dec 31, 2019)
19-50908580-G-C		Inborn genetic diseases	Uncertain significance (Mar 23, 2023)
19-50908596-C-T		Amelogenesis imperfecta type 2A1	Likely pathogenic (Mar 25, 2024)
19-50908611-C-A		Amelogenesis imperfecta type 2A1	Uncertain significance (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLK4	protein_coding	protein_coding	ENST00000324041	5	4387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000454	0.412	125695	1	52	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0312	147	148	0.993	0.00000927	1645
Missense in Polyphen		65	62.431	1.0412		684
Synonymous	-0.464	72	67.2	1.07	0.00000520	505
Loss of Function	0.484	9	10.7	0.840	4.80e-7	111

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00205	0.00199
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000705	0.0000703
Middle Eastern	0.000217	0.000217
South Asian	0.0000980	0.0000980
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a major role in enamel formation (PubMed:15235027). Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix (By similarity). {ECO:0000250|UniProtKB:Q9Z0M1, ECO:0000269|PubMed:15235027}.
• Disease: DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A1 (AI2A1) [MIM:204700]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:15235027}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling (Consensus)

Intolerance Scores

• loftool: 0.252
• rvis_EVS: 0.48
• rvis_percentile_EVS: 79.25

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.220
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0415

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klk4
• Phenotype: skeleton phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: proteolysis;extracellular matrix disassembly;biomineral tissue development;amelogenesis
• Cellular component: extracellular region;secretory granule
• Molecular function: serine-type endopeptidase activity;protein binding;serine-type peptidase activity;metal ion binding