TPP2

tripeptidyl peptidase 2

Basic information

Region (hg38): 13:102596958-102679958

Links

ENSG00000134900

∙ NCBI:7174 ∙ OMIM:190470 ∙ HGNC:12016 ∙ Uniprot:P29144 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome (Supportive), mode of inheritance: AR
immunodeficiency 78 with autoimmunity and developmental delay (Moderate), mode of inheritance: AR
immunodeficiency 78 with autoimmunity and developmental delay (Strong), mode of inheritance: AR
immunodeficiency 78 with autoimmunity and developmental delay (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 78 with autoimmunity and developmental delay	AR	Allergy/Immunology/Infectious	Among other findings, the condition can involve early-onset immunodeficiency, with severe and recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; BMT has been described	Allergy/Immunology/Infectious; Hematologic; Neurologic	25525876; 25414442; 33586135

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPP2 gene.

Evans_syndrome,_immunodeficiency,_and_premature_immunosenescence_associated_with_tripeptidyl-peptidase_II_deficiency (665 variants)
Inborn_genetic_diseases (97 variants)
not_provided (23 variants)
Immunodeficiency_78_with_autoimmunity_and_developmental_delay (15 variants)
TPP2-related_disorder (14 variants)
not_specified (2 variants)
Recurrent_lower_respiratory_tract_infections (1 variants)
Thrombocytopenia (1 variants)
Global_developmental_delay (1 variants)
Recurrent_upper_respiratory_tract_infections (1 variants)
See_cases (1 variants)
Acute_otitis_media (1 variants)
Cutis_marmorata (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001330588.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	216 clinvar	6 clinvar	228
missense	1 clinvar		287 clinvar	6 clinvar	2 clinvar	296
nonsense	6 clinvar	1 clinvar				7
start loss						0
frameshift	6 clinvar	1 clinvar				7
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	13	4	293	222	8

Highest pathogenic variant AF is 0.000006571425

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPP2	protein_coding	protein_coding	ENST00000376065	29	82169

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000883	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.86	374	651	0.574	0.0000323	8156
Missense in Polyphen		76	226.53	0.33549		2790
Synonymous	-0.389	245	237	1.03	0.0000128	2380
Loss of Function	6.28	10	64.4	0.155	0.00000323	841

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000193	0.000183
Ashkenazi Jewish	0.000300	0.000298
East Asian	0.000112	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000981	0.0000967
Middle Eastern	0.000112	0.000109
South Asian	0.0000657	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. May be able to complement the 26S proteasome function to some extent under conditions in which the latter is inhibited. Stimulates adipogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.176

Intolerance Scores

loftool: 0.0666
rvis_EVS: -1.15
rvis_percentile_EVS: 6.27

Haploinsufficiency Scores

pHI: 0.471
hipred: Y
hipred_score: 0.580
ghis: 0.633

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.463

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tpp2
Phenotype: hematopoietic system 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); immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);

Gene ontology

Biological process: protein polyubiquitination;proteolysis
Cellular component: nucleoplasm;cytoplasm;cytosol;nuclear body
Molecular function: endopeptidase activity;aminopeptidase activity;serine-type endopeptidase activity;protein binding;tripeptidyl-peptidase activity;identical protein binding