TSPO2

Summary

TSPO2 (translocator protein 2, HGNC:21256) is a protein-coding gene on chromosome 6p21.1, encoding Translocator protein 2 (Q5TGU0). Cholesterol-binding protein involved in the redistribution of cholesterol from lipid droplets to the endoplasmic reticulum.

Enables 5-aminolevulinic acid transmembrane transporter activity. Involved in 5-aminolevulinic acid import across plasma membrane. Located in organelle membrane and plasma membrane.

Source: NCBI Gene 222642 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001010873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21256
Approved symbol	TSPO2
Name	translocator protein 2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ34B21.2
Ensembl gene	ENSG00000112212
Ensembl biotype	protein_coding
OMIM	619409
Entrez	222642

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000373158, ENST00000373161, ENST00000470917

RefSeq mRNA: 2 — MANE Select: NM_001010873 NM_001010873, NM_001159726

CCDS: CCDS34444

Canonical transcript exons

ENST00000373161 — 4 exons

Exon	Start	End
ENSE00000750657	41043557	41043698
ENSE00001459681	41042966	41043158
ENSE00001459682	41042467	41042778
ENSE00001820779	41043940	41044337

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 87.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0525 / max 43.5445, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67722	0.0325	4
67723	0.0199	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	87.22	gold quality
bone marrow	UBERON:0002371	85.12	gold quality
bone marrow cell	CL:0002092	73.64	gold quality
blood	UBERON:0000178	69.15	gold quality
Brodmann (1909) area 10	UBERON:0013541	68.66	gold quality
mononuclear cell	CL:0000842	65.48	gold quality
monocyte	CL:0000576	65.46	gold quality
leukocyte	CL:0000738	63.01	gold quality
sural nerve	UBERON:0015488	61.26	gold quality
cerebellar vermis	UBERON:0004720	58.83	gold quality
jejunal mucosa	UBERON:0000399	58.66	silver quality
gall bladder	UBERON:0002110	57.79	gold quality
duodenum	UBERON:0002114	57.71	gold quality
endometrium epithelium	UBERON:0004811	57.39	gold quality
islet of Langerhans	UBERON:0000006	56.23	gold quality
adult mammalian kidney	UBERON:0000082	55.98	gold quality
right lobe of liver	UBERON:0001114	55.66	gold quality
liver	UBERON:0002107	55.52	gold quality
upper leg skin	UBERON:0004262	55.41	silver quality
body of stomach	UBERON:0001161	55.40	gold quality
small intestine	UBERON:0002108	54.83	gold quality
thymus	UBERON:0002370	54.67	silver quality
small intestine Peyer’s patch	UBERON:0003454	54.62	gold quality
stomach	UBERON:0000945	53.63	gold quality
quadriceps femoris	UBERON:0001377	53.47	gold quality
metanephros	UBERON:0000081	52.91	gold quality
paraflocculus	UBERON:0005351	52.73	gold quality
epithelium of esophagus	UBERON:0001976	52.66	gold quality
mucosa of stomach	UBERON:0001199	52.54	gold quality
vastus lateralis	UBERON:0001379	52.42	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	138.78
E-HCAD-9	yes	6.51
E-MTAB-9067	yes	4.66
E-HCAD-10	no	1.96
E-ANND-3	no	1.29
E-MTAB-9467	no	0.62

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• identify the TSPO2 family of proteins as mediators of cholesterol redistribution-dependent erythroblast maturation during mammalian erythropoiesis (PMID:19729679)
• TSPO ligands can induce Plasmodium falciparum death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of reactive oxygen species. (PMID:27641616)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspo	ENSDARG00000026655
mus_musculus	Tspo2	ENSMUSG00000023995
rattus_norvegicus	Tspo2	ENSRNOG00000050521
drosophila_melanogaster	Tspo	FBGN0031263
caenorhabditis_elegans	tspo-1	WBGENE00077771

Paralogs (1): TSPO (ENSG00000100300)

Protein

Protein identifiers

Translocator protein 2 — Q5TGU0 (reviewed: Q5TGU0)

Alternative names: Peripheral-type benzodiazepine receptor-like protein 1

All UniProt accessions (1): Q5TGU0

UniProt curated annotations — full annotation on UniProt →

Function. Cholesterol-binding protein involved in the redistribution of cholesterol from lipid droplets to the endoplasmic reticulum. Required to meet cholesterol demands during erythropoietic differentiation. May play a role in transport processes at the plasma membrane of erythrocytes, including regulating VDAC-mediated ATP export, and import of the heme precursors protoporphyrin IX and 5-aminolevulinic acid.

Subunit / interactions. Homotetramer. May also form homodimer.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Tissue specificity. Expressed in erythrocytes (at protein level).

Domain organisation. The C-terminal region mediates cholesterol-binding.

Similarity. Belongs to the TspO/BZRP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TGU0-1	1	yes
Q5TGU0-2	2

RefSeq proteins (2): NP_001010873, NP_001153198 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004307	TspO_MBR	Family
IPR038330	TspO/MBR-related_sf	Homologous_superfamily

Pfam: PF03073

UniProt features (8 total): transmembrane region 5, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TGU0-F1	68.09	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MORF_RAGE, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GNF2_ANK1, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GNF2_SPTA1, GNF2_PCAF, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT

GO Biological Process (5): intracellular cholesterol transport (GO:0032367), lipid droplet organization (GO:0034389), enucleate erythrocyte differentiation (GO:0043353), import across plasma membrane (GO:0098739), 5-aminolevulinic acid import across plasma membrane (GO:0140484)

GO Molecular Function (3): cholesterol binding (GO:0015485), 5-aminolevulinic acid transmembrane transporter activity (GO:0140485), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), organelle membrane (GO:0031090), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	2
intracellular anatomical structure	1
cholesterol transport	1
intracellular sterol transport	1
organelle organization	1
erythrocyte differentiation	1
transmembrane transport	1
import into cell	1
monocarboxylic acid transport	1
nitrogen compound transport	1
amino acid import across plasma membrane	1
carboxylic acid transmembrane transport	1
sterol binding	1
alcohol binding	1
monocarboxylic acid transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
binding	1
mitochondrial membrane	1
organelle outer membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell periphery	1
membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPO2	VDAC1	P21796	652
TSPO2	EPS8L1	Q8TE68	516
TSPO2	STAR	P49675	462
TSPO2	FAM174B	Q3ZCQ3	421
TSPO2	TMCC2	O75069	407
TSPO2	PRKACA	P17612	385
TSPO2	KLF1	Q13351	382
TSPO2	GYPB	P06028	377
TSPO2	GYPA	P02724	376
TSPO2	GYPE	P15421	375
TSPO2	PRKACG	P22612	365
TSPO2	PRKACB	P22694	363
TSPO2	UNC5A	Q6ZN44	355
TSPO2	NBR1	Q14596	353
TSPO2	CRYGN	Q8WXF5	344

IntAct

179 interactions, top by confidence:

A	B	Type	Score
TSPO2	CERS4	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	EMP1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	FXYD3	psi-mi:“MI:0915”(physical association)	0.560
TSPO2		psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	MFF	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	GGT7	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SPAG4	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	AHNAK2	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	ASZ1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	LRRC59	psi-mi:“MI:0915”(physical association)	0.560
ASGR2	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	RETREG3	psi-mi:“MI:0915”(physical association)	0.560
CD69	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
SLC34A2	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
BIK	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
KLRC1	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
ERP29	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	TSPO2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (62): TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), TSPO2 (Two-hybrid), SLC41A3 (Two-hybrid)

ESM2 similar proteins: A0A067DFU5, A0A0E3D8L0, A0A0E3D8M3, A0A0U5GIU9, A0A140JWS9, A0A194XJW1, A0A1V6NYL5, E2RDM9, E3UBL5, F5HGH8, F5HHT6, O82245, O94327, O94440, P09723, P0CU77, P0DXH1, P0DXW0, P0DXW1, P16257, P30535, P50637, P58872, P58873, P97689, P9WEQ3, Q07764, Q0C8A7, Q0C9L5, Q0D2G3, Q10255, Q13336, Q2KIB3, Q5AR23, Q5R9A6, Q5RFN8, Q5TGU0, Q5U4Q2, Q6GNM0, Q6TEK3

Diamond homologs: E2RDM9, P16257, P30535, P30536, P50637, Q5TGU0, Q6UN27, Q9CRZ8, Q9GMC9, O28797, O82245, O94327, P17057, Q81BL7, Q8KBX2, Q9RFC8, O34694

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TSPO2	“up-regulates activity”	SLC25A4	binding
TSPO2	“up-regulates activity”	VDAC1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

495 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41042672:G:GT	donor_gain	0.9900
6:41042749:G:GT	donor_gain	0.9900
6:41042759:G:GT	donor_gain	0.9900
6:41042767:G:GT	donor_gain	0.9900
6:41042775:C:T	donor_gain	0.9800
6:41043934:GCCCA:G	acceptor_loss	0.9700
6:41043935:CCCA:C	acceptor_loss	0.9700
6:41043936:CCAGG:C	acceptor_loss	0.9700
6:41043937:CAGG:C	acceptor_loss	0.9700
6:41043938:A:G	acceptor_loss	0.9700
6:41043939:G:GC	acceptor_loss	0.9700
6:41042840:G:GT	donor_gain	0.9600
6:41042673:A:T	donor_gain	0.9500
6:41042851:G:GG	donor_gain	0.9500
6:41043154:GTGGG:G	donor_gain	0.9500
6:41043156:GGG:G	donor_gain	0.9500
6:41043157:GG:G	donor_gain	0.9500
6:41043157:GGG:G	donor_gain	0.9500
6:41043157:GGGTG:G	donor_loss	0.9500
6:41043158:GG:G	donor_gain	0.9500
6:41043159:GTGA:G	donor_loss	0.9500
6:41043160:TGAG:T	donor_loss	0.9500
6:41043161:GAGTA:G	donor_loss	0.9500
6:41043162:AGT:A	donor_loss	0.9500
6:41042759:G:T	donor_gain	0.9400
6:41042768:A:T	donor_gain	0.9400
6:41043163:G:C	donor_loss	0.9300
6:41042770:A:G	donor_gain	0.9200
6:41043938:A:AG	acceptor_gain	0.9200
6:41043939:G:GG	acceptor_gain	0.9200

AlphaMissense

1064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41043651:A:C	S90R	0.921
6:41043653:C:A	S90R	0.921
6:41043653:C:G	S90R	0.921
6:41043157:G:C	G58R	0.897
6:41044045:T:A	W141R	0.891
6:41044045:T:C	W141R	0.891
6:41043994:T:A	W124R	0.890
6:41043994:T:C	W124R	0.890
6:41043979:A:C	S119R	0.886
6:41043981:C:A	S119R	0.886
6:41043981:C:G	S119R	0.886
6:41043158:G:A	G58D	0.880
6:41043654:T:A	W91R	0.859
6:41043654:T:C	W91R	0.859
6:41043028:G:A	G15R	0.844
6:41043028:G:C	G15R	0.844
6:41044034:C:G	P137R	0.836
6:41044034:C:A	P137H	0.817
6:41044016:C:A	A131D	0.811
6:41043562:C:A	A60D	0.805
6:41043007:T:C	F8L	0.799
6:41043009:T:A	F8L	0.799
6:41043009:T:G	F8L	0.799
6:41043574:T:A	V64E	0.788
6:41043967:G:A	G115R	0.777
6:41043967:G:C	G115R	0.777
6:41043571:T:C	L63P	0.770
6:41043643:T:C	L87P	0.769
6:41043565:C:A	S61Y	0.739
6:41043158:G:T	G58V	0.738

dbSNP variants (sampled 300 via entrez): RS1000039207 (6:41039841 C>T), RS1000324590 (6:41043577 G>A), RS1000412179 (6:41039586 A>G), RS1001019051 (6:41041005 C>G), RS1001840857 (6:41042851 G>A), RS1003107755 (6:41044305 C>T), RS1003283233 (6:41039724 T>C), RS1003486167 (6:41044493 C>T), RS1004295642 (6:41044820 G>A), RS1004599419 (6:41039898 C>T), RS1004757984 (6:41040301 A>G), RS1005194373 (6:41040040 A>G,T), RS1005536260 (6:41041718 G>C), RS1006458113 (6:41041555 A>G), RS1006638464 (6:41042134 T>C,G)

Disease associations

OMIM: gene MIM:619409 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003007_1	Non-cardia gastric cancer	3.000000e-08
GCST003010_4	Gastric cancer	7.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	increases activity, affects binding, decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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