TYSND1

protein-coding

trypsin like peroxisomal matrix peptidase 1

Gene summary

This gene encodes a protease that removes the N-terminal peroxisomal targeting signal (PTS2) from proteins produced in the cytosol, thereby facilitating their import into the peroxisome. The encoded protein is also capable of removing the C-terminal peroxisomal targeting signal (PTS1) from proteins in the peroxisomal matrix. The full-length protein undergoes self-cleavage to produce shorter, potentially inactive, peptides. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

MANE transcript

NM_173555.4

Inheritance

—

ClinVar variants

U:110B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr10:70,137,981-70,146,700

External References & Databases

Ensembl (ENSG00000156521)

Transcript & Mutation Effects

hg38 • Region Span ~8.7 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 TYSND1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173555.4. 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			1 clinvar	1 clinvar		2
missense			106 clinvar	1 clinvar		107
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	110	2	0	112

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173555.4	RefSeq	NP_775826.2	4	MANE Select
ENST00000287078.7	Ensembl	ENSP00000287078.6	4	MANE Select
NM_001040273.3	RefSeq	NP_001035363.1	2	Standard
ENST00000335494.5	Ensembl	ENSP00000335673.5	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Peroxisomal protein import
TYSND1 cleaves peroxisomal proteins

Biological Process

proteolysis
protein targeting to peroxisome
protein processing
regulation of fatty acid beta-oxidation
protein homooligomerization

Molecular Function

protease binding
serine-type endopeptidase activity

Cellular Component

peroxisome
peroxisomal matrix
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287078
Coding exons: 4
Length: 8696
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.975	238	284	0.837	0.0000154	3466
Missense (PolyPhen)		80	90.999	0.87913		1135
Synonymous	2.75	91	131	0.695	0.00000738	1278
Loss of Function	1.57	7	13.1	0.533	5.70e-7	147

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000055	0.000053	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Peroxisomal protease that mediates both the removal of the leader peptide from proteins containing a PTS2 target sequence and processes several PTS1-containing proteins. Catalyzes the processing of PTS1-proteins involved in the peroxisomal beta- oxidation of fatty acids. {ECO:0000269|PubMed:22002062}.;

Recessive Scores

pRec: 0.109

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.670

Gene Damage Prediction

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