TPP2

Summary

TPP2 (tripeptidyl peptidase 2, HGNC:12016) is a protein-coding gene on chromosome 13q33.1, encoding Tripeptidyl-peptidase 2 (P29144). Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway.

This gene encodes a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. The protein has a specialized function that is essential for some MHC class I antigen presentation. The protein is a high molecular mass serine exopeptidase; the amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class rather than the trypsin class.

Source: NCBI Gene 7174 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 78 with autoimmunity and developmental delay (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 860 total — 17 pathogenic, 4 likely-pathogenic (top 4% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 7 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 11 (q < 0.05)
• Phenotypes (HPO): 30
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.29 (highly constrained)
• MANE Select transcript: NM_001330588

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12016
Approved symbol	TPP2
Name	tripeptidyl peptidase 2
Location	13q33.1
Locus type	gene with protein product
Status	Approved
Aliases	TPPII
Ensembl gene	ENSG00000134900
Ensembl biotype	protein_coding
OMIM	190470
Entrez	7174

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 15 retained_intron, 14 nonsense_mediated_decay, 13 protein_coding, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000376052

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2, TSL 5: 3

ENST00000376052, ENST00000376065, ENST00000466153, ENST00000482393, ENST00000490010, ENST00000490420, ENST00000493770, ENST00000496126, ENST00000650757, ENST00000651448, ENST00000651544, ENST00000651748, ENST00000651823, ENST00000651921, ENST00000652033, ENST00000652308, ENST00000698381, ENST00000698382, ENST00000698383, ENST00000698384, ENST00000698385, ENST00000698386, ENST00000698387, ENST00000698388, ENST00000698389, ENST00000698390, ENST00000698391, ENST00000698392, ENST00000698393, ENST00000854161, ENST00000912746, ENST00000959512, ENST00001008644, ENST00001008645, ENST00001054861, ENST00001054862, ENST00001054863, ENST00001054864, ENST00001089795, ENST00001089796, ENST00001089797, ENST00001089798, ENST00001089799, ENST00001089800, ENST00001114176

RefSeq mRNA: 3 — MANE Select: NM_001330588 NM_001330588, NM_001367947, NM_003291

CCDS: CCDS81777, CCDS9502

Canonical transcript exons

ENST00000376052 — 30 exons

Exon	Start	End
ENSE00000917076	102636224	102636392
ENSE00001469250	102651359	102651397
ENSE00003973486	102649408	102649486
ENSE00003973488	102644557	102644673
ENSE00003973489	102596986	102597203
ENSE00003973490	102643222	102643376
ENSE00003973491	102676296	102676415
ENSE00003973492	102648907	102649151
ENSE00003973495	102604793	102604921
ENSE00003973497	102627848	102627924
ENSE00003973498	102640270	102640376
ENSE00003973499	102616396	102616500
ENSE00003973500	102627012	102627166
ENSE00003973501	102638239	102638315
ENSE00003973504	102678227	102679958
ENSE00003973505	102674283	102674490
ENSE00003973508	102663648	102663744
ENSE00003973509	102664795	102664925
ENSE00003973511	102633950	102634098
ENSE00003973513	102622877	102623040
ENSE00003973516	102629482	102629609
ENSE00003973517	102646294	102646390
ENSE00003973518	102618722	102618846
ENSE00003973519	102647207	102647344
ENSE00003973520	102657056	102657207
ENSE00003973521	102635587	102635702
ENSE00003973523	102637082	102637239
ENSE00003973524	102644909	102645009
ENSE00003973526	102630096	102630195
ENSE00003973527	102614101	102614196

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.2460 / max 531.6882, expressed in 1823 samples.

Highest expression (Bgee): testis, sperm, calcaneal tendon, male germ cell, colonic epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TPP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	sqtl	8.3e-11	-0.51	13:102677662:C:T
Adipose Subcutaneous	sqtl	5.4e-10	-0.41	13:102659348:A:T
Whole Blood	eqtl	3.4e-08	+0.09	13:102684075:A:T
Skin Sun Exposed Lower leg	sqtl	3.4e-08	-0.41	13:102637059:A:G
Muscle Skeletal	eqtl	5.5e-08	-0.15	13:102727286:A:C
Breast Mammary Tissue	sqtl	5.1e-05	-0.40	13:102677662:C:T
Nerve Tibial	sqtl	5.9e-05	-0.32	13:102637059:A:G
Esophagus Gastroesophageal Junction	eqtl	1.2e-04	+0.17	13:102598836:C:G
Thyroid	eqtl	3.6e-04	+0.10	13:102614644:G:A
Cells EBV-transformed lymphocytes	sqtl	3.7e-04	-0.47	13:102637059:A:G
Lung	sqtl	5.0e-04	+0.42	13:102602691:A:C
Testis	sqtl	7.2e-04	+0.37	13:102672957:A:G
Colon Transverse	eqtl	9.0e-04	+0.14	13:102599006:G:A
Artery Tibial	sqtl	1.1e-03	-0.28	13:102659348:A:T
Testis	eqtl	1.7e-03	+0.09	13:102603875:T:TAGG
Ovary	sqtl	3.1e-03	+0.72	13:102645983:AGTT:A
Breast Mammary Tissue	eqtl	4.9e-03	-0.13	13:101972738:A:G
Artery Tibial	eqtl	6.8e-03	+0.20	13:102586116:T:C
Cells EBV-transformed lymphocytes	eqtl	8.3e-03	+1.07	13:102290730:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-02	-0.43	13:103426877:A:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
135919	38.3767	1822
135918	3.4497	1338
135917	2.6065	1129
135920	0.7449	459
135923	0.0408	6
135924	0.0274	3

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.52	gold quality
right testis	UBERON:0004534	97.19	gold quality
testis	UBERON:0000473	96.48	gold quality
sperm	CL:0000019	96.44	gold quality
calcaneal tendon	UBERON:0003701	96.35	gold quality
male germ cell	CL:0000015	94.98	gold quality
colonic epithelium	UBERON:0000397	94.52	gold quality
monocyte	CL:0000576	94.41	gold quality
mononuclear cell	CL:0000842	94.24	gold quality
rectum	UBERON:0001052	94.04	gold quality
leukocyte	CL:0000738	94.03	gold quality
adrenal tissue	UBERON:0018303	93.79	gold quality
tendon	UBERON:0000043	93.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.22	gold quality
right uterine tube	UBERON:0001302	92.99	gold quality
right lung	UBERON:0002167	92.99	gold quality
gastrocnemius	UBERON:0001388	92.98	gold quality
muscle of leg	UBERON:0001383	92.93	gold quality
right ovary	UBERON:0002118	92.80	gold quality
ventricular zone	UBERON:0003053	92.74	gold quality
right lobe of thyroid gland	UBERON:0001119	92.68	gold quality
left ovary	UBERON:0002119	92.66	gold quality
seminal vesicle	UBERON:0000998	92.65	gold quality
left lobe of thyroid gland	UBERON:0001120	92.52	gold quality
upper lobe of left lung	UBERON:0008952	92.47	gold quality
bone marrow cell	CL:0002092	92.35	gold quality
mucosa of stomach	UBERON:0001199	92.35	gold quality
tibial nerve	UBERON:0001323	92.32	gold quality
thyroid gland	UBERON:0002046	92.22	gold quality
spleen	UBERON:0002106	92.21	gold quality
upper lobe of lung	UBERON:0008948	92.06	gold quality
cortical plate	UBERON:0005343	91.98	gold quality
body of uterus	UBERON:0009853	91.92	gold quality
right lobe of liver	UBERON:0001114	91.89	gold quality
body of pancreas	UBERON:0001150	91.86	gold quality
ganglionic eminence	UBERON:0004023	91.78	gold quality
endocervix	UBERON:0000458	91.77	gold quality
granulocyte	CL:0000094	91.76	gold quality
lymph node	UBERON:0000029	91.75	gold quality
left uterine tube	UBERON:0001303	91.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.66	gold quality
ectocervix	UBERON:0012249	91.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.55	gold quality
transverse colon	UBERON:0001157	91.43	gold quality
muscle organ	UBERON:0001630	91.37	gold quality
adipose tissue	UBERON:0001013	91.26	gold quality
connective tissue	UBERON:0002384	91.22	gold quality
omental fat pad	UBERON:0010414	91.08	gold quality
peritoneum	UBERON:0002358	91.07	gold quality
ovary	UBERON:0000992	91.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.06	gold quality
vermiform appendix	UBERON:0001154	91.04	gold quality
gall bladder	UBERON:0002110	91.03	gold quality
skin of abdomen	UBERON:0001416	91.00	gold quality
bone marrow	UBERON:0002371	90.88	gold quality
cerebellar hemisphere	UBERON:0002245	90.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.72	gold quality
cerebellar cortex	UBERON:0002129	90.70	gold quality
skin of leg	UBERON:0001511	90.67	gold quality
diaphragm	UBERON:0001103	90.66	gold quality
left coronary artery	UBERON:0001626	90.63	gold quality
corpus epididymis	UBERON:0004359	90.61	gold quality
tibial artery	UBERON:0007610	90.58	gold quality
oocyte	CL:0000023	90.57	gold quality
popliteal artery	UBERON:0002250	90.56	gold quality
descending thoracic aorta	UBERON:0002345	90.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.46	gold quality
small intestine	UBERON:0002108	90.45	gold quality
endometrium	UBERON:0001295	90.44	gold quality
right atrium auricular region	UBERON:0006631	90.42	gold quality
colon	UBERON:0001155	90.40	gold quality
intestine	UBERON:0000160	90.39	gold quality
vagina	UBERON:0000996	90.36	gold quality
pancreas	UBERON:0001264	90.32	gold quality
bronchial epithelial cell	CL:0002328	90.29	gold quality
corpus callosum	UBERON:0002336	90.28	gold quality
large intestine	UBERON:0000059	90.25	gold quality
minor salivary gland	UBERON:0001830	90.23	gold quality
aorta	UBERON:0000947	90.19	gold quality
metanephros cortex	UBERON:0010533	90.14	gold quality
coronary artery	UBERON:0001621	90.13	gold quality
body of stomach	UBERON:0001161	90.10	gold quality
caecum	UBERON:0001153	90.01	gold quality
sigmoid colon	UBERON:0001159	89.92	gold quality
right coronary artery	UBERON:0001625	89.91	gold quality
stomach	UBERON:0000945	89.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.86	gold quality
uterus	UBERON:0000995	89.83	gold quality
thoracic aorta	UBERON:0001515	89.79	gold quality
ascending aorta	UBERON:0001496	89.78	gold quality
embryo	UBERON:0000922	89.77	gold quality
female reproductive system	UBERON:0000474	89.75	gold quality
cardiac atrium	UBERON:0002081	89.70	gold quality
triceps brachii	UBERON:0001509	89.66	gold quality
lower esophagus	UBERON:0013473	89.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.61	gold quality
zone of skin	UBERON:0000014	89.54	gold quality
liver	UBERON:0002107	89.39	gold quality
skeletal muscle tissue	UBERON:0001134	89.29	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.56
E-ANND-3	yes	10.13
E-GEOD-93593	yes	5.07
E-GEOD-110499	no	378.94

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	45.8	high
Bone marrow	tissue	29.0	low
Caudate putamen	tissue	27.4
Cerebral cortex	tissue	26.6	high
Somatosensory cortex	tissue	26.6
Occipital cortex	tissue	26.4
Cerebellum	tissue	25.9	high
Frontal cortex	tissue	25.1
Motor cortex	tissue	24.7
Hippocampal formation	tissue	24.4
Retrosplenial and cingulate cortex	tissue	23.6
Olfactory bulb	tissue	23.4
Prefrontal cortex	tissue	22.7
Putamen	tissue	22.7
Retrosplenial cortex	tissue	22.3
Superior colliculi	tissue	22.1
Temporal cortex	tissue	22.0
Pons	tissue	21.8
Thalamus	tissue	21.4
Entorhinal cortex	tissue	21.4
Skeletal muscle	tissue	21.3	medium
Insular cortex	tissue	21.2
Midbrain	tissue	20.5
Medulla oblongata	tissue	20.2
Ventral forebrain	tissue	20.2
Amygdala	tissue	19.6
Tongue	tissue	19.5
Septum	tissue	19.3
Basal ganglia	tissue	18.9	high
Hypothalamus	tissue	18.9
Periaqueductal gray	tissue	18.6
Substantia nigra	tissue	18.3
Liver	tissue	17.2	high
Spinal cord	tissue	17.2
Corpus callosum	tissue	17.1
Thyroid gland	tissue	16.3	medium
Choroid plexus	tissue	15.9
Rectum	tissue	15.3	high
Lymph node	tissue	14.8	high
Seminal vesicle	tissue	14.8	medium
Placenta	tissue	14.7	high
Spleen	tissue	14.6	low
Retina	tissue	14.4
Nucleus accumbens	tissue	14.0
Tonsil	tissue	13.9	medium
Thymus	tissue	13.6
Breast	tissue	13.5	medium
Epididymis	tissue	13.5	high
Endometrium 1	tissue	12.3	medium
Lung	tissue	12.0	medium
Colon	tissue	11.8	high
Postcentral gyrus	tissue	11.8
Heart muscle	tissue	11.6	medium
Locus coeruleus	tissue	11.4
Hippocampus	tissue	11.2	high
Urinary bladder	tissue	11.1	high
Appendix	tissue	11.1	high
Cervix	tissue	11.0	medium
Smooth muscle	tissue	10.6	low
Esophagus	tissue	10.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal hippocampus (24.4), Ventral hippocampus (22.6), Subiculum (21.0), Cerebellar cortex (20.4), Parieto-temporal junction (white matter) (20.4).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.29, missense Z 4.58 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000376052 splits into 7 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:102,597,039–102,627,872	300 / 398.3	0.75	no
13:102,627,873–102,634,075	63 / 165.7	0.38	no
13:102,634,076–102,647,231	325 / 463.7	0.70	no
13:102,647,232–102,647,300	4 / 24.4	0.16	yes (p 3.5e-05)
13:102,647,301–102,664,848	179 / 274.7	0.65	no
13:102,664,849–102,676,303	116 / 117.3	0.99	no
13:102,676,304–102,678,313	41 / 78.3	0.52	no

Literature-anchored findings (GeneRIF, showing 20)

• the promoter could be localized to a 215 bp fragment upstream of the initiation codon. (PMID:15716107)
• TPPII appears to promote malignant cell growth by allowing exit from mitosis and the survival of cells with severe mitotic spindle damage. (PMID:16762321)
• TPP2 plays a specialized role in antigen processing and one that is not essential for the generation of most presented peptides. (PMID:16849449)
• This investigation reveals that TPP II expression could be regulated through both positive and negative regulatory elements. (PMID:17343995)
• Expression of mRNA for MuRF-1 increased approximately 3-fold at 10 days without changes in MAFbx or tripeptidyl peptidase II mRNA, but all decreased between 10 and 21 days of muscle disuse. (PMID:17901116)
• Results indicate that TPPII is dispensable for the generation of proteasome-dependent HLA class I ligands and, the enzyme is not involved significantly in generating the proteasome-independent HLA-B27-bound peptide repertoire. (PMID:18286573)
• Cross-presentation of NY-ESO-1/ISCOMATRIX cancer vaccine was proteasome independent and requires the cytosolic protease tripeptidyl peptidase II. (PMID:19155470)
• MHC class I-restricted LMP1 epitopes studied in this work are two of very few epitopes known to date to be processed proteasome independently by tripeptidyl peptidase II. (PMID:19587004)
• Results suggest an important function of TPPII in the maintenance of viral growth and may have implications for anti-viral therapy. (PMID:21134372)
• Current knowledge about TPPII with a focus on structural aspects. (PMID:21771670)
• Previously unknown differences between TPP II orthologues and subtilisin as well as features that might be conserved within the entire family of subtilisin-like serine peptidases. (PMID:22266401)
• obtained a 3D structure of the human TPPII (PMID:22483107)
• Study showed that overexpression of Tripeptidyl peptidase II (TPP2) occurs frequently during oral carcinogenesis and might be associated with the progression of Oral Squamous Cell Carcinoma (OSCC) via Spindle Assembly Checkpoint(SAC) activation. (PMID:22986808)
• TPPII, MYBBP1A and CDK2 form a protein-protein interaction network. (PMID:25303791)
• Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with TPP2 deficiency have been described in two consanguineous siblings. (PMID:25414442)
• Study found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans. (PMID:25525876)
• TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. (PMID:26041847)
• Novel interactions of TPPII, p53, and SIRT7 presented in this study might contribute to the knowledge of the regulatory effects of these proteins on apoptotic pathways and to the understanding mechanisms of aging and lifespan regulation. (PMID:26169984)
• Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene. (PMID:33586135)
• Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence. (PMID:35466366)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpp2	ENSDARG00000078751
mus_musculus	Tpp2	ENSMUSG00000041763
rattus_norvegicus	Tpp2	ENSRNOG00000011194
drosophila_melanogaster	TppII	FBGN0020370
caenorhabditis_elegans		WBGENE00017686

Paralogs (9): PCSK5 (ENSG00000099139), PCSK4 (ENSG00000115257), PCSK2 (ENSG00000125851), PCSK6 (ENSG00000140479), FURIN (ENSG00000140564), MBTPS1 (ENSG00000140943), PCSK7 (ENSG00000160613), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:102724) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 34 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	2
decreased leukocyte cell number	1
extramedullary hematopoiesis	1
focal hair loss	1
abnormal spleen morphology	1
enlarged lymph nodes	1
abnormal immune system cell morphology	1
weight loss	1
disheveled coat	1
abnormal antigen presentation	1
abnormal level of surface class I molecules	1
premature death	1
abnormal immune system organ morphology	1
abnormal cell cycle	1
thymus atrophy	1
increased autoantibody level	1
premature aging	1
abnormal lymphocyte physiology	1
increased anti-nuclear antigen antibody level	1
increased B cell number	1
increased T cell number	1
decreased T cell number	1
abnormal cytotoxic T cell physiology	1
increased double-negative T cell number	1
decreased double-positive T cell number	1

+9 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A5PK39	96.6%	Diamond
Arabidopsis thaliana	F4JVN6	65.5%	Diamond
Oryza sativa Japonica Group	Q6ESI7	65.4%	Diamond
Schizosaccharomyces pombe 972h-	Q9UT05	35.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FGF14-AS1	ncRNA	100874081
METTL21C	protein-coding	196541
FGF14	protein-coding	2259
FGF14-IT1	ncRNA	283480
FGF14-AS2	ncRNA	283481
LRTM3	protein-coding	643677
TEX30	protein-coding	93081
MIR2681	ncRNA	100616110
MIR4705	ncRNA	100616239
LINC00411	ncRNA	100874161
NALCN-AS1	ncRNA	100885778
NALCN	protein-coding	259232
ITGBL1	protein-coding	9358

Protein

Protein identifiers

Tripeptidyl-peptidase 2 — P29144 (reviewed: P29144)

Alternative names: Tripeptidyl aminopeptidase, Tripeptidyl-peptidase II

All UniProt accessions (10): A0A494C0A3, A0A494C0U1, A0A494C0X4, A0A494C159, A0A494C1B8, A0A494C1L2, A0A494C1S4, A0A494C1S6, P29144, Q5VZU9

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. It plays an important role in intracellular amino acid homeostasis. Stimulates adipogenesis.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Immunodeficiency 78 with autoimmunity and developmental delay (IMD78) [MIM:619220] An autosomal recessive disorder characterized by immune dysregulation, increased susceptibility to bacterial, viral and fungal infections, recurrent sinopulmonary or skin infections, and autoimmune abnormalities including hemolytic anemia and autoimmune cytopenias. Patients also have global developmental delay with speech delay and variable intellectual disability. Disease onset is in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The limitation of proteolytic products to tripeptides is achieved by tailoring the size of the substrate-binding cleft: the two negatively charged residues Glu-305 and Glu-331 that are blocking position P4 limit the number of residues that can be accommodated in the binding cleft and thus create a molecular ruler. At the same time, they orient substrates so that the tripeptides are removed exclusively from the N-terminus.

Similarity. Belongs to the peptidase S8 family.

RefSeq proteins (3): NP_001317517, NP_001354876, NP_003282 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000209	Peptidase_S8/S53_dom	Domain
IPR015500	Peptidase_S8_subtilisin-rel	Family
IPR022229	TPPII_Ig-like-2	Domain
IPR022232	TPPII_C_art	Domain
IPR022398	Peptidase_S8_His-AS	Active_site
IPR023828	Peptidase_S8_Ser-AS	Active_site
IPR034051	TPP_II_domain	Domain
IPR036852	Peptidase_S8/S53_dom_sf	Homologous_superfamily
IPR046939	TPPII_C_sf	Homologous_superfamily
IPR046940	TPPII_Ig-like_sf	Homologous_superfamily
IPR048383	TPPII_Ig-like-1	Domain
IPR048384	TPPII_GBD	Domain
IPR050131	Peptidase_S8_subtilisin-like	Family

Pfam: PF00082, PF12580, PF12583, PF21223, PF21316

Enzyme classification (BRENDA)

• EC 3.4.14.10 — tripeptidyl-peptidase II (BRENDA: 16 organisms, 80 substrates, 143 inhibitors, 120 Km, 111 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ALA-L-ALA-L-ALA 4-NITROANILIDE	0.008–20	30
L-ALA-L-ALA-L-PHE 4-NITROANILIDE	0.017–30	30
ALA-ALA-PHE-4-NITROANILIDE	0.012–0.88	25
ALA-ALA-ALA-4-NITROANILIDE	0.0036–0.13	24
ALA-ALA-PHE-7-AMIDO-4-METHYLCOUMARIN	0.11–0.47	3
ARG-ARG-ALA-(PHOSPHO)SER-VAL-ALA	0.008–0.015	3
L-ALA-L-ALA-L-PHE-P-NITROANILIDE	0.013–1	3
ALA-ALA-PHE 4-METHYLCOUMARIN 7-AMIDE	0.016	1
ALA-ALA-PHE-P-NITROANILIDE	0.02	1

UniProt features (16 total): sequence variant 4, modified residue 3, active site 3, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29144-F1	91.98	0.80

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nuclear bodies

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3)

Position	Role
44	charge relay system
264	charge relay system
449	charge relay system

Post-translational modifications (3)

Type	Positions
Phosphoserine	915
N-acetylalanine	2
N6-acetyllysine	401

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-983169	Class I MHC mediated antigen processing & presentation	—
R-HSA-168256	Immune System	—

MSigDB gene sets: 249 (showing top): FREAC2_01, HNF3ALPHA_Q6, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MORF_BRCA1, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, ONKEN_UVEAL_MELANOMA_UP, KONDO_COLON_CANCER_HCP_WITH_H3K27ME1, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (3): protein polyubiquitination (GO:0000209), proteolysis (GO:0006508), intracellular amino acid homeostasis (GO:0080144)

GO Molecular Function (10): endopeptidase activity (GO:0004175), aminopeptidase activity (GO:0004177), serine-type endopeptidase activity (GO:0004252), tripeptidyl-peptidase activity (GO:0008240), identical protein binding (GO:0042802), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), exopeptidase activity (GO:0008238), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), nucleus (GO:0005634)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

20 GO namespaces:

Category	Terms
peptidase activity	3
cellular anatomical structure	2
protein ubiquitination	1
protein metabolic process	1
intracellular chemical homeostasis	1
exopeptidase activity	1
endopeptidase activity	1
serine-type peptidase activity	1
serine-type exopeptidase activity	1
protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular amino acid homeostasis	BP	mutant phenotype
cytosol	CC	direct assay
nuclear body	CC	direct assay
aminopeptidase activity	MF	mutant phenotype
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,036 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPP2	ERAP2	Q6P179	879
TPP2	ERAP1	Q9NZ08	852
TPP2	THOP1	P52888	624
TPP2	BLMH	Q13867	558
TPP2	NRDC	O43847	554
TPP2	LNPEP	Q9UIQ6	552
TPP2	COL3A1	P02461	550
TPP2	NPEPPS	P55786	508
TPP2	TAPBP	O15533	468
TPP2	CAST	P20810	427
TPP2	LRBA	P50851	420
TPP2	DPP3	Q9NY33	417
TPP2	TPP1	O14773	416
TPP2	CCK	P06307	416
TPP2	IDE	P14735	407

IntAct

Human interaction partners of TPP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
POLB	physical association	0.780	8
EHHADH	physical association	0.670	5
PPP1R16A	physical association	0.670	4
NCALD	association	0.530	2
DOK3	association	0.530	1
CHIA	association	0.350	2
PTPRD	association	0.350	1
SNX2	association	0.350	1
TAS2R31	association	0.350	1
VDR	association	0.350	1
ZNF75A	association	0.350	1
HLA-B	physical association	0.000	1
MCC	physical association	0.000	1
MTNR1A	physical association	0.000	1

BioGRID (156 interactions; top human partners by supporting records): C9orf41 (Affinity Capture-MS; 3 records), CHIA (Affinity Capture-MS; 3 records), CYP1A1 (Affinity Capture-MS; 3 records), DENND2D (Affinity Capture-MS; 3 records), DOK3 (Affinity Capture-MS; 3 records), ALOX5 (Affinity Capture-MS; 2 records), CDH19 (Affinity Capture-MS; 2 records), CSE1L (Co-fractionation; 2 records), GTF2E2 (Affinity Capture-MS; 2 records), KBTBD7 (Affinity Capture-MS; 2 records), KLHL36 (Affinity Capture-MS; 2 records), NAA40 (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PCDHGB4 (Affinity Capture-MS; 2 records), POLB (Two-hybrid; 2 records)

Disease & clinical

Genetic variants

Variant evidence for TPP2: 860 ClinVar records (21 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

860 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	4
Uncertain significance	350
Likely benign	407
Benign	35

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 21 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
650988	NM_001330588.2(TPP2):c.2433_2434insA (p.Val812fs)	Pathogenic	criteria provided, single submitter	1
663284	NM_001330588.2(TPP2):c.2843del (p.Pro948fs)	Pathogenic	criteria provided, single submitter	1
1076853	NM_001330588.2(TPP2):c.2420T>G (p.Leu807Ter)	Pathogenic	criteria provided, single submitter	1
2100401	NM_001330588.2(TPP2):c.2619T>G (p.Tyr873Ter)	Pathogenic	criteria provided, single submitter	1
2413358	NM_001330588.2(TPP2):c.3466_3467del (p.Gly1156fs)	Pathogenic	criteria provided, single submitter	1
2817462	NM_001330588.2(TPP2):c.1844dup (p.Tyr616fs)	Pathogenic	criteria provided, single submitter	1
2856662	NM_001330588.2(TPP2):c.3071C>G (p.Ser1024Ter)	Pathogenic	criteria provided, single submitter	1
2878736	NM_001330588.2(TPP2):c.1320_1321del (p.Gly441fs)	Pathogenic	criteria provided, single submitter	1
2880480	NM_001330588.2(TPP2):c.3244C>T (p.Arg1082Ter)	Pathogenic	criteria provided, single submitter	1
3726063	NM_001330588.2(TPP2):c.2563C>T (p.Gln855Ter)	Pathogenic	criteria provided, single submitter	1
4736460	NM_001330588.2(TPP2):c.1066del (p.Tyr356fs)	Pathogenic	criteria provided, single submitter	1
583012	NM_001330588.2(TPP2):c.2952+1G>C	Likely pathogenic	criteria provided, single submitter	1
1476641	NM_001330588.2(TPP2):c.2873+1G>A	Likely pathogenic	criteria provided, single submitter	1
1804520	NM_001330588.2(TPP2):c.2665C>T (p.Arg889Ter)	Likely pathogenic	criteria provided, single submitter	1
4292206	NM_001330588.2(TPP2):c.3012del (p.Tyr1005fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TPP2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 3,729):

Position(s)	Effect	Δscore	Sites
13:102604785–102604786	acceptor_gain	1.0000	2
13:102604792	acceptor_loss	1.0000
13:102604922–102604923	donor_loss	1.0000	5
13:102614099–102614100	acceptor_loss	1.0000	4
13:102614186	donor_gain	1.0000
13:102614197–102614198	donor_loss	1.0000	4
13:102616394–102616395	acceptor_loss	1.0000	3
13:102622875–102622876	acceptor_loss	1.0000	6
13:102622972	donor_gain	1.0000
13:102627148	donor_gain	1.0000

AlphaMissense

3,636 missense substitutions predicted likely pathogenic (of 8,283 scored), across 933 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M450	9	0.997	1.000
M391	9	0.984	0.999
M392	9	0.976	0.997
M445	9	0.970	1.000
M304	9	0.953	0.996
M589	9	0.873	0.994
D44	8	0.999	1.000
H264	8	0.999	1.000
H267	8	0.999	1.000
N362	8	0.999	1.000
D48	8	0.996	0.999
S328	8	0.996	1.000
N446	8	0.995	1.000
D69	8	0.994	0.999
D298	8	0.994	0.999
D871	8	0.992	0.998
H691	8	0.988	0.999
S359	8	0.984	1.000
D75	8	0.973	0.993
D811	8	0.971	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	8.24e-07
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000129
Glioblastoma Multiforme (validation)	favorable	0.000398

Disease associations

OMIM: gene MIM:190470 | disease phenotypes: MIM:619220

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 78 with autoimmunity and developmental delay	Definitive	Autosomal recessive	4
autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
immunodeficiency 78 with autoimmunity and developmental delay	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
COVID-19 research	green
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Leukodystrophy, adult onset	amber

Mondo (3): immunodeficiency 78 with autoimmunity and developmental delay (MONDO:0030971), thrombocytopenia (MONDO:0002049), autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome (MONDO:0018636)

HPO phenotypes

30 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000265	Mastoiditis
HP:0000403	Recurrent otitis media
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001297	Stroke
HP:0001744	Splenomegaly
HP:0001878	Hemolytic anemia
HP:0001888	Decreased total lymphocyte count
HP:0001890	Autoimmune hemolytic anemia
HP:0001904	Autoimmune neutropenia
HP:0001973	Autoimmune thrombocytopenia
HP:0002110	Bronchiectasis
HP:0002716	Lymphadenopathy
HP:0002725	Systemic lupus erythematosus
HP:0002783	Recurrent lower respiratory tract infections
HP:0002960	Autoimmunity
HP:0003237	Increased circulating IgG concentration
HP:0003496	Increased circulating IgM concentration
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0006268	Fluctuating splenomegaly
HP:0011342	Mild global developmental delay
HP:0011343	Moderate global developmental delay
HP:0011463	Childhood onset
HP:0011947	Respiratory tract infection
HP:0012115	Hepatitis
HP:0032247	Persistent CMV viremia
HP:0040167	Facial papilloma
HP:0410028	Recurrent oral herpes

GWAS associations

1 associations:

Study	Trait	p-value
GCST90002404_128	Red cell distribution width	3e-11

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6156 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S8: Subtilisin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
example 8 [WO1999033801A1]	Inhibition	9.44	pKi
peptide 4 [PMID: 18294843]	Inhibition	7.7	pKi

Binding affinities (BindingDB)

2 measured of 2 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL263633	KI	20 nM
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 6 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Ki	20	nM	CHEMBL263633
6.31	Kd	486.9	nM	CHEMBL5653589
6.31	ED50	486.9	nM	CHEMBL5653589
5.52	IC50	2990	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 12 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-2-[2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]prop-2-enoylamino]-3-methylbutanoyl]amino]propanoic acid	329747: Inhibition of human tripeptidyl peptidase2 from erythrocytes	ki	0.0200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149646: Binding affinity to human TPP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.4869	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178788: Inhibition of TPP2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	2.9900	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
arsenite	affects binding, decreases reaction	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
vanadyl sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	affects localization, decreases reaction	1
SB 203580	affects localization, decreases reaction	1
U 0126	affects localization, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Dinitrochlorobenzene	affects binding	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652688	Binding	Binding affinity to human TPP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1R3	Abcam K-562 TPP2 KO	Cancer cell line	Female
CVCL_D2MQ	Abcam Raji TPP2 KO	Cancer cell line	Male
CVCL_WQ73	Abcam Jurkat TPP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TPP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.