TPD52L2

Summary

TPD52L2 (TPD52 like 2, HGNC:12007) is a protein-coding gene on chromosome 20q13.33, encoding Tumor protein D54 (O43399).

This gene encodes a member of the tumor protein D52-like family. These proteins are characterized by an N-terminal coiled-coil motif that is used to form homo- and heteromeric complexes with other tumor protein D52-like proteins. Expression of this gene may be a marker for breast cancer and acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 12.

Source: NCBI Gene 7165 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_003288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12007
Approved symbol	TPD52L2
Name	TPD52 like 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	D54, hD54, TPD54
Ensembl gene	ENSG00000101150
Ensembl biotype	protein_coding
OMIM	603747
Entrez	7165

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 24 protein_coding, 1 retained_intron

ENST00000217121, ENST00000346249, ENST00000348257, ENST00000351424, ENST00000352482, ENST00000358548, ENST00000369927, ENST00000474176, ENST00000611972, ENST00000615907, ENST00000879320, ENST00000879321, ENST00000879322, ENST00000879323, ENST00000879324, ENST00000938339, ENST00000938340, ENST00000938341, ENST00000938342, ENST00000938343, ENST00000938344, ENST00000938345, ENST00000941623, ENST00000941624, ENST00000941625

RefSeq mRNA: 10 — MANE Select: NM_003288 NM_001243891, NM_001243892, NM_001243894, NM_001243895, NM_003288, NM_199359, NM_199360, NM_199361, NM_199362, NM_199363

CCDS: CCDS13540, CCDS13541, CCDS13542, CCDS13543, CCDS13544, CCDS13545, CCDS58785, CCDS74752, CCDS74753

Canonical transcript exons

ENST00000346249 — 7 exons

Exon	Start	End
ENSE00000663595	63875816	63875875
ENSE00000856651	63869296	63869441
ENSE00003696222	63889190	63889238
ENSE00003696831	63882719	63882820
ENSE00003702059	63873668	63873816
ENSE00003901516	63865270	63865384
ENSE00003902253	63889850	63891538

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.4134 / max 839.9839, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185884	73.0299	1825
185885	23.3835	1814

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.89	gold quality
right coronary artery	UBERON:0001625	97.54	gold quality
lower esophagus	UBERON:0013473	97.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.45	gold quality
ascending aorta	UBERON:0001496	97.37	gold quality
thoracic aorta	UBERON:0001515	97.37	gold quality
popliteal artery	UBERON:0002250	97.36	gold quality
tibial artery	UBERON:0007610	97.36	gold quality
aorta	UBERON:0000947	97.33	gold quality
stromal cell of endometrium	CL:0002255	97.26	gold quality
descending thoracic aorta	UBERON:0002345	97.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.19	gold quality
mucosa of stomach	UBERON:0001199	97.09	gold quality
esophagus	UBERON:0001043	97.07	gold quality
left coronary artery	UBERON:0001626	97.02	gold quality
esophagus mucosa	UBERON:0002469	96.91	gold quality
coronary artery	UBERON:0001621	96.80	gold quality
smooth muscle tissue	UBERON:0001135	96.59	gold quality
ectocervix	UBERON:0012249	96.55	gold quality
left uterine tube	UBERON:0001303	96.53	gold quality
monocyte	CL:0000576	96.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.51	gold quality
endocervix	UBERON:0000458	96.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.44	gold quality
cerebellar hemisphere	UBERON:0002245	96.35	gold quality
right adrenal gland	UBERON:0001233	96.30	gold quality
left adrenal gland	UBERON:0001234	96.30	gold quality
cerebellar cortex	UBERON:0002129	96.27	gold quality
right adrenal gland cortex	UBERON:0035827	96.22	gold quality
left adrenal gland cortex	UBERON:0035825	96.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting TPD52L2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538

Literature-anchored findings (GeneRIF, showing 9)

• The results indicate that tumor protein D52-like 2 genes are not ubiquitously expressed in leukemic bone marrow in children, and that RNA sample parameters may influence measures of gene expression more than commonly appreciated. (PMID:16620967)
• TPD54 may serve as a novel biomarker for oral squamous cell carcinoma. (PMID:23529586)
• hABCF3 positively regulates cell proliferation, at least partially through the interaction with a tumor protein D52 protein family member: TPD52L2. (PMID:24052230)
• tpd54 overexpression in SAS cells significantly decreased colony formation in an anchorage-independent manner. Additionally, knock-down of tpd54 enhanced the number of colonies formed and overexpression of tpd52 in tpd54 knock-down cells increased the size of the colonies formed. The chemotaxis assay showed that tpd54 overexpression decreased cell migration (PMID:28339026)
• the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification. (PMID:28798933)
• these results suggest a critical role of miR-217 in suppressing proliferation, migration and invasion of pancreatic adenocarcinoma (HPAC)cell by targeting Tpd52l2. Targeting the miR-217/Tpd52l2 axis may be a new therapeutic application with which to treat patients with HPAC in the future. (PMID:29039566)
• TPD52L2 is an important biomarker influencing glioblastoma prognosis (PMID:29106517)
• Intracellular wetting mediates contacts between liquid compartments and membrane-bound organelles. (PMID:34427635)
• Investigation of Transcript Variant 6 of TPD52L2 as a Prognostic and Predictive Biomarker in Basal-Like MDA-MB-231 and MDA-MB-453 Cell Lines for Breast Cancer. (PMID:36071863)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpd52l2b	ENSDARG00000013655
danio_rerio	tpd52l2a	ENSDARG00000027154
mus_musculus	Tpd52l2	ENSMUSG00000000827
rattus_norvegicus	Tpd52l2	ENSRNOG00000080504
drosophila_melanogaster	CG5174	FBGN0034345
caenorhabditis_elegans		WBGENE00008745

Paralogs (3): TPD52 (ENSG00000076554), TPD52L1 (ENSG00000111907), TPD52L3 (ENSG00000170777)

Protein

Protein identifiers

Tumor protein D54 — O43399 (reviewed: O43399)

Alternative names: Tumor protein D52-like 2

All UniProt accessions (5): O43399, A0A087WYR3, A0A087WZ51, Q68E05, Q6FGS1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Forms a homodimer or heterodimer with other members of the family. Interacts with MAL2.

Similarity. Belongs to the TPD52 family.

Isoforms (7)

UniProt ID	Names	Canonical?
O43399-1	1, HD54+ins2	yes
O43399-2	2, HD54-ins2
O43399-3	3
O43399-4	4
O43399-5	5
O43399-6	6
O43399-7	7

RefSeq proteins (10): NP_001230820, NP_001230821, NP_001230823, NP_001230824, NP_003279, NP_955391, NP_955392, NP_955393, NP_955394, NP_955395 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007327	TPD52	Family
IPR012341	6hp_glycosidase-like_sf	Homologous_superfamily

Pfam: PF04201

UniProt features (25 total): modified residue 13, splice variant 5, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43399-F1	70.10	0.15

Functional residue map

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

Post-translational modifications (13): 21, 96, 149, 161, 163, 166, 173, 192, 195, 1, 3, 12, 19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, MODULE_151, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GTGCCTT_MIR506, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, LIAO_METASTASIS, PEART_HDAC_PROLIFERATION_CLUSTER_UP, TGCCTTA_MIR124A, IIZUKA_LIVER_CANCER_PROGRESSION_G1_G2_DN, MODULE_114, WANG_BARRETTS_ESOPHAGUS_AND_ESOPHAGUS_CANCER_DN, YAGI_AML_WITH_11Q23_REARRANGED, JAIN_NFKB_SIGNALING, CAGCTTT_MIR320

GO Biological Process (2): carbohydrate metabolic process (GO:0005975), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (3): RNA binding (GO:0003723), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
primary metabolic process	1
cell population proliferation	1
regulation of cellular process	1
nucleic acid binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPD52L2	MAL2	Q969L2	923
TPD52L2	MALL	Q13021	810
TPD52L2	TPD52L1	Q16890	498
TPD52L2	YIF1A	O95070	473
TPD52L2	PYROXD2	Q8N2H3	435
TPD52L2	PIGR	P01833	413
TPD52L2	NUB1	Q9Y5A7	408
TPD52L2	KLK10	O43240	404
TPD52L2	EP400	Q96L91	396
TPD52L2	LRCH3	Q96II8	383
TPD52L2	ABHD16B	Q9H3Z7	380
TPD52L2	WDR83OS	Q9Y284	367
TPD52L2	CD59	P13987	357
TPD52L2	PPP5C	P53041	354
TPD52L2	RAB11A	P24410	351

IntAct

76 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TPD52L2	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
TPD52L2	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
TPD52L2	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
TPD52L3	TPD52L2	psi-mi:“MI:0914”(association)	0.530
TPD52L1	TPD52L2	psi-mi:“MI:0914”(association)	0.530
TPD52	TPD52L2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
MAP1LC3A	TPD52L2	psi-mi:“MI:0915”(physical association)	0.400
MAP1LC3B	TPD52L2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ADORA2B	TPD52L2	psi-mi:“MI:0915”(physical association)	0.370
APP	TPD52L2	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
FXR1	TPD52L2	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350

BioGRID (224): SH3GLB1 (Two-hybrid), TPD52L2 (Affinity Capture-RNA), TPD52L2 (Affinity Capture-RNA), TPD52L2 (Affinity Capture-MS), TPD52L2 (Affinity Capture-MS), TPD52L2 (Affinity Capture-MS), CTH (Co-fractionation), ECHS1 (Co-fractionation), HSD17B10 (Co-fractionation), OGT (Co-fractionation), PAFAH1B2 (Co-fractionation), PPM1G (Co-fractionation), PTGES3 (Co-fractionation), SEC31A (Co-fractionation), TARS (Co-fractionation)

ESM2 similar proteins: A0A1B0GVV1, A0M8U1, A6H6W9, A6QPI6, B1AZA5, D3ZXD8, D4ABL6, E1BWM5, E9PV86, F1QH17, G3MWR8, O43399, P01134, P01135, Q0X0A5, Q1RLU8, Q29S14, Q2PG42, Q3KNM2, Q3SZB3, Q3ZC24, Q3ZCQ8, Q4R3C7, Q5RAJ8, Q5RBB8, Q5RCT1, Q5SQY2, Q5ZJ41, Q5ZJB7, Q6AYJ2, Q6DN14, Q6GM44, Q6ZVM7, Q75Q41, Q7RTP6, Q8BR65, Q8CJ19, Q8IVP5, Q8K1Z0, Q8TF64

Diamond homologs: O43399, O54818, P55326, P55327, Q16890, Q5RCT1, Q62393, Q6PCT3, Q95212, Q96J77, Q9CYZ2, Q9I8F4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Infectious disease	9	4.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1897 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63869426:GGC:G	donor_gain	1.0000
20:63873813:GCGC:G	donor_gain	1.0000
20:63875871:GACCT:G	donor_gain	1.0000
20:63887546:T:TA	acceptor_gain	1.0000
20:63865380:CCAAG:C	donor_loss	0.9900
20:63865381:CAAG:C	donor_loss	0.9900
20:63865382:AAG:A	donor_loss	0.9900
20:63865383:AGG:A	donor_loss	0.9900
20:63865384:GGTAC:G	donor_loss	0.9900
20:63865385:G:GC	donor_loss	0.9900
20:63865386:T:A	donor_loss	0.9900
20:63873662:TTGCA:T	acceptor_loss	0.9900
20:63873663:TGCA:T	acceptor_loss	0.9900
20:63873664:GCA:G	acceptor_loss	0.9900
20:63873665:CA:C	acceptor_loss	0.9900
20:63873666:AGG:A	acceptor_loss	0.9900
20:63873815:GC:G	donor_gain	0.9900
20:63873817:G:GG	donor_gain	0.9900
20:63875876:G:GG	donor_gain	0.9900
20:63887540:T:A	acceptor_gain	0.9900
20:63887550:A:AG	acceptor_gain	0.9900
20:63887550:AT:A	acceptor_gain	0.9900
20:63887551:T:G	acceptor_gain	0.9900
20:63887551:T:TA	acceptor_gain	0.9900
20:63889186:A:AG	acceptor_gain	0.9900
20:63889186:AAAG:A	acceptor_gain	0.9900
20:63889188:A:AG	acceptor_gain	0.9900
20:63889188:A:C	acceptor_loss	0.9900
20:63889189:G:GG	acceptor_gain	0.9900
20:63889189:G:GT	acceptor_loss	0.9900

AlphaMissense

1326 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63873712:G:C	K70N	0.998
20:63873712:G:T	K70N	0.998
20:63882772:C:A	A143D	0.998
20:63882796:T:A	I151N	0.997
20:63873690:T:C	L63P	0.996
20:63882750:G:C	A136P	0.996
20:63873707:G:C	A69P	0.994
20:63873702:T:C	L67P	0.993
20:63869434:T:C	L53P	0.992
20:63882771:G:C	A143P	0.992
20:63873690:T:A	L63Q	0.990
20:63873693:G:C	R64P	0.990
20:63882720:T:G	Y126D	0.990
20:63889203:T:C	F164L	0.989
20:63889205:C:A	F164L	0.989
20:63889205:C:G	F164L	0.989
20:63882796:T:G	I151S	0.988
20:63889225:T:A	V171D	0.988
20:63873732:T:C	L77P	0.987
20:63875847:T:A	W116R	0.987
20:63875847:T:C	W116R	0.987
20:63882742:T:A	L133H	0.987
20:63889204:T:C	F164S	0.987
20:63873711:A:T	K70M	0.986
20:63875817:T:G	Y106D	0.986
20:63882751:C:A	A136E	0.986
20:63875829:T:C	S110P	0.985
20:63882784:T:A	V147E	0.985
20:63882787:G:A	G148D	0.985
20:63882796:T:C	I151T	0.985

dbSNP variants (sampled 300 via entrez): RS1000030152 (20:63870337 C>T), RS1000065092 (20:63887418 G>A,T), RS1000315122 (20:63867030 C>G,T), RS1000332900 (20:63886386 AG>A), RS1000514892 (20:63886801 C>T), RS1000540233 (20:63871403 G>T), RS1000615355 (20:63866102 T>C), RS1000686825 (20:63867278 C>G,T), RS1000773765 (20:63879050 C>T), RS1000809166 (20:63867367 A>C), RS1000926319 (20:63870778 T>C,G), RS1000976324 (20:63885256 A>G), RS1001013734 (20:63874331 C>T), RS1001027307 (20:63876575 A>G), RS1001054404 (20:63865838 T>G)

Disease associations

OMIM: gene MIM:603747 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066421 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
isobutyl alcohol	affects cotreatment, affects expression, increases abundance	1
M-VAC protocol	decreases response to substance	1
beta-methylcholine	affects expression	1
phenethyl isothiocyanate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
pyrachlostrobin	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases methylation	1
Aspirin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652683	Binding	Binding affinity to human TPD52L2 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

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.