KLK11

protein-coding

kallikrein related peptidase 11, the group of Kallikreins|Serine proteases

Gene summary

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed. [provided by RefSeq, Dec 2016]

Previous symbols:

PRSS20

MANE transcript

NM_001136032.3

Inheritance

ClinVar variants

P:2U:39B:2

Top phenotype

Ichthyosis with erythrokeratoderma

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr19:51,022,216-51,028,039

External References & Databases

Ensembl (ENSG00000167757)

Transcript & Mutation Effects

hg38 • Region Span ~5.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ichthyosis with erythrokeratodermaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957783

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ichthyosis with erythrokeratodermaAD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 36689511; 37212630

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLK11 variants in ClinVar

3 Conditions Cataloged

Inborn genetic diseasesTotal: 36

Ichthyosis with erythrokeratodermaTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136032.3. 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	2 clinvar		37 clinvar	2 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	39	2	0	43

Highest pathogenic variant AF is 0.0000065700433

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136032.3	RefSeq	NP_001129504.1	5	MANE Select
ENST00000453757.8	Ensembl	ENSP00000413958.2	5	MANE Select
NM_001167605.2	RefSeq	NP_001161077.1	5	Standard
NM_006853.3	RefSeq	NP_006844.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity
serine-type peptidase activity

Cellular Component

extracellular space
Golgi apparatus
secretory granule
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000594768
Coding exons: 6
Length: 5824
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125747
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.677	139	163	0.851	0.00000986	1785
Missense (PolyPhen)		53	67.676	0.78314		757
Synonymous	-0.804	75	66.6	1.13	0.00000423	560
Loss of Function	1.62	7	13.4	0.523	8.07e-7	137

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible multifunctional protease. Efficiently cleaves 'bz-Phe-Arg-4-methylcoumaryl-7-amide', a kallikrein substrate, and weakly cleaves other substrates for kallikrein and trypsin. Cleaves synthetic peptides after arginine but not lysine residues. {ECO:0000269|PubMed:10872828, ECO:0000269|PubMed:16467084}.;

Intolerance Scores

LoFtool: 0.0579
RVIS EVS: 0.89
RVIS percentile EVS: 89.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.124

Gene Damage Prediction

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