ST14

protein-coding

ST14 transmembrane serine protease matriptase, the group of Type II transmembrane serine proteases

Gene summary

The protein encoded by this gene is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is found to be activated by sphingosine 1-phosphate. This protease has been shown to cleave and activate hepatocyte growth factor/scattering factor, and urokinase plasminogen activator, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors. The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis. [provided by RefSeq, Jul 2008]

Previous symbols:

PRSS14

MANE transcript

NM_021978.4

Inheritance

ClinVar variants

P:15U:136B:89

Top phenotype

Ichthyosis, congenital, autosomal recessive 11

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr11:130,159,782-130,210,362

External References & Databases

Ensembl (ENSG00000149418)

Transcript & Mutation Effects

hg38 • Region Span ~50.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive congenital ichthyosis 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011218

Submitter: Genomics England PanelApp

autosomal recessive congenital ichthyosis 11SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011218

Submitter: Orphanet

autosomal recessive congenital ichthyosis 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011218

Submitter: PanelApp Australia

autosomal recessive congenital ichthyosis 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011218

Submitter: G2P

autosomal recessive congenital ichthyosis 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011218

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Ichthyosis, congenital, autosomal recessive 11AR

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: 17273967; 18445049; 18843291

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ST14 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 132

Inborn genetic diseasesTotal: 120

ST14-related disorderTotal: 20

not specifiedTotal: 17

Autosomal recessive congenital ichthyosis 11Total: 8

High myopiaTotal: 1

IchthyosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021978.4. 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			3 clinvar	51 clinvar	9 clinvar	63
missense	1 clinvar	1 clinvar	127 clinvar	20 clinvar	9 clinvar	158
nonsense	2 clinvar	1 clinvar				3
start loss	1 clinvar					1
frameshift	3 clinvar	2 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	6 clinvar			10
Total	8	7	136	71	18	240

Highest pathogenic variant AF is 0.000018588811

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021978.4	RefSeq	NP_068813.1	19	MANE Select
ENST00000278742.6	Ensembl	ENSP00000278742.5	19	MANE Select
ENST00000894126.1	Ensembl	ENSP00000564185.1	19	Standard
ENST00000894126.2	Ensembl	ENSP00000564185.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MicroRNAs in cancer - Homo sapiens (human)
Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

neural tube closure
proteolysis
keratinocyte differentiation
epithelial cell morphogenesis involved in placental branching
cornification

Molecular Function

endopeptidase activity
serine-type endopeptidase activity
serine-type peptidase activity

Cellular Component

extracellular space
plasma membrane
integral component of plasma membrane
basolateral plasma membrane
extrinsic component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000278742
Coding exons: 19
Length: 50815
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	457	539	0.848	0.0000385	5582
Missense (PolyPhen)		121	202.74	0.59682		2114
Synonymous	0.378	237	245	0.969	0.0000203	1646
Loss of Function	4.71	9	41.9	0.215	0.00000205	481

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing. {ECO:0000269|PubMed:18843291}.;
Disease: DISEASE: Ichthyosis, congenital, autosomal recessive 11 (ARCI11) [MIM:602400]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:17273967, ECO:0000269|PubMed:18843291}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.336

Intolerance Scores

LoFtool: 0.0733
RVIS EVS: -0.35
RVIS percentile EVS: 29.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.800

Gene Damage Prediction

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