TPP2

tripeptidyl peptidase 2

Basic information

Region (hg38): 13:102596957-102679958

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

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 (516 variants)
• Inborn genetic diseases (29 variants)
• not specified (24 variants)
• not provided (13 variants)
• Immunodeficiency 78 with autoimmunity and developmental delay (10 variants)
• See cases (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.

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			7	143	8	158
missense			227	3	3	233
nonsense	2	1				3
start loss						0
frameshift	3					3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region			13	31	6	50
non coding			6	74	26	106
Total	5	3	241	220	37

Highest pathogenic variant AF is 0.00000657

Variants in TPP2

This is a list of pathogenic ClinVar variants found in the TPP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-102597044-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Nov 08, 2017)
13-102597047-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Oct 13, 2023)
13-102597047-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Feb 16, 2023)
13-102597050-T-A		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Oct 20, 2023)
13-102597059-G-A		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Jan 20, 2023)
13-102597065-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Oct 17, 2022)
13-102597068-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Dec 18, 2023)
13-102597077-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Dec 13, 2022)
13-102597086-G-T		TPP2-related disorder	Likely benign (Jul 15, 2019)
13-102597101-C-A		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (May 15, 2023)
13-102597104-A-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Nov 23, 2022)
13-102597108-G-A		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Sep 02, 2022)
13-102597110-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Apr 04, 2022)
13-102597111-T-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency • Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
13-102597112-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Jan 29, 2019)
13-102597120-T-G		Immunodeficiency 78 with autoimmunity and developmental delay	Uncertain significance (Feb 19, 2022)
13-102597125-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Jun 20, 2018)
13-102597129-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency • Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
13-102597129-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Oct 24, 2022)
13-102597130-C-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Dec 11, 2023)
13-102597143-G-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Jan 22, 2023)
13-102597145-G-C		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Aug 09, 2022)
13-102597149-G-T		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Likely benign (Dec 09, 2023)
13-102597153-C-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Oct 30, 2022)
13-102597156-A-G		Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency	Uncertain significance (Dec 13, 2021)

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