TPRA1

Summary

TPRA1 (transmembrane protein adipocyte associated 1, HGNC:30413) is a protein-coding gene on chromosome 3q21.3, encoding Transmembrane protein adipocyte-associated 1 (Q86W33).

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within embryonic cleavage and negative regulation of mitotic cell cycle phase transition. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 131601 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001136053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30413
Approved symbol	TPRA1
Name	transmembrane protein adipocyte associated 1
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	TPRA40, FLJ32197, TMEM227
Ensembl gene	ENSG00000163870
Ensembl biotype	protein_coding
OMIM	608336
Entrez	131601

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 67 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296210, ENST00000355552, ENST00000393400, ENST00000450633, ENST00000462228, ENST00000465915, ENST00000469111, ENST00000483868, ENST00000489960, ENST00000490290, ENST00000490643, ENST00000648957, ENST00000860376, ENST00000860377, ENST00000860378, ENST00000860379, ENST00000860380, ENST00000860381, ENST00000860382, ENST00000860383, ENST00000860384, ENST00000860385, ENST00000860386, ENST00000860387, ENST00000860388, ENST00000860389, ENST00000860390, ENST00000860391, ENST00000860392, ENST00000860393, ENST00000860394, ENST00000860395, ENST00000860396, ENST00000860397, ENST00000860398, ENST00000860399, ENST00000860400, ENST00000860401, ENST00000860402, ENST00000860403, ENST00000860404, ENST00000924285, ENST00000924286, ENST00000924287, ENST00000924288, ENST00000924289, ENST00000924290, ENST00000924291, ENST00000924292, ENST00000924293, ENST00000924294, ENST00000924295, ENST00000924296, ENST00000965985, ENST00000965986, ENST00000965987, ENST00000965988, ENST00000965989, ENST00000965990, ENST00000965991, ENST00000965992, ENST00000965993, ENST00000965994, ENST00000965995, ENST00000965996, ENST00000965997, ENST00000965998, ENST00000965999, ENST00000966000, ENST00000966001

RefSeq mRNA: 9 — MANE Select: NM_001136053 NM_001136053, NM_001142646, NM_001353001, NM_001353002, NM_001353003, NM_001353004, NM_001353005, NM_001353006, NM_001353007

CCDS: CCDS3042, CCDS46899

Canonical transcript exons

ENST00000355552 — 11 exons

Exon	Start	End
ENSE00001079166	127575749	127575809
ENSE00001412003	127590410	127590733
ENSE00001667859	127576821	127576893
ENSE00001671057	127576617	127576696
ENSE00001693185	127571232	127573788
ENSE00001766788	127579740	127579872
ENSE00001799732	127576990	127577076
ENSE00003518814	127575185	127575265
ENSE00003561778	127575403	127575505
ENSE00003784060	127575940	127576050
ENSE00003791923	127580022	127580163

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 94.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0625 / max 154.0232, expressed in 1807 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44374	11.5036	1788
44371	5.4810	1742
44375	1.6159	926
44378	0.7995	470
44372	0.6060	354
44370	0.0565	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	94.95	gold quality
endocervix	UBERON:0000458	94.22	gold quality
skin of leg	UBERON:0001511	93.87	gold quality
stromal cell of endometrium	CL:0002255	93.81	gold quality
skin of abdomen	UBERON:0001416	93.43	gold quality
body of uterus	UBERON:0009853	93.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.71	gold quality
right ovary	UBERON:0002118	92.67	gold quality
ectocervix	UBERON:0012249	92.62	gold quality
left ovary	UBERON:0002119	92.49	gold quality
apex of heart	UBERON:0002098	92.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.13	gold quality
right lobe of thyroid gland	UBERON:0001119	92.02	gold quality
cerebellar hemisphere	UBERON:0002245	92.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.98	gold quality
lower esophagus	UBERON:0013473	91.97	gold quality
left lobe of thyroid gland	UBERON:0001120	91.90	gold quality
left uterine tube	UBERON:0001303	91.83	gold quality
cerebellar cortex	UBERON:0002129	91.74	gold quality
left adrenal gland	UBERON:0001234	91.73	gold quality
right adrenal gland	UBERON:0001233	91.66	gold quality
metanephros cortex	UBERON:0010533	91.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.65	gold quality
left adrenal gland cortex	UBERON:0035825	91.65	gold quality
nerve	UBERON:0001021	91.59	gold quality
tibial nerve	UBERON:0001323	91.59	gold quality
right lobe of liver	UBERON:0001114	91.58	gold quality
right uterine tube	UBERON:0001302	91.52	gold quality
right adrenal gland cortex	UBERON:0035827	91.42	gold quality
body of stomach	UBERON:0001161	91.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.31

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Gpr175 is a novel positive regulator of the Hh signaling pathway (PMID:26451044)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpra1	ENSDARG00000054930
mus_musculus	Tpra1	ENSMUSG00000002871
rattus_norvegicus	Tpra1	ENSRNOG00000016665
caenorhabditis_elegans		WBGENE00008366

Protein

Protein identifiers

Transmembrane protein adipocyte-associated 1 — Q86W33 (reviewed: Q86W33)

Alternative names: Integral membrane protein GPR175, Transmembrane protein 227

All UniProt accessions (5): Q86W33, C9JU06, C9JVW5, C9JZ00, F8WC44

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Ubiquitous, with higher levels in heart, placenta and kidney.

Similarity. Belongs to the UPF0359 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86W33-1	1	yes
Q86W33-2	2
Q86W33-3	3

RefSeq proteins (9): NP_001129525, NP_001136118, NP_001339930, NP_001339931, NP_001339932, NP_001339933, NP_001339934, NP_001339935, NP_001339936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018781	TPRA1/CAND2/CAND8	Family

Pfam: PF10160

UniProt features (16 total): transmembrane region 7, splice variant 4, glycosylation site 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W33-F1	74.08	0.41

Functional residue map

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

Glycosylation sites (3): 361, 11, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MITOTIC_CELL_CYCLE, GOBP_LIPID_METABOLIC_PROCESS, chr3q21, GOBP_EMBRYO_DEVELOPMENT, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_DIVISION

GO Biological Process (4): lipid metabolic process (GO:0006629), G protein-coupled receptor signaling pathway (GO:0007186), embryonic cleavage (GO:0040016), negative regulation of mitotic cell cycle phase transition (GO:1901991)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
G protein-coupled receptor activity	1
signal transduction	1
embryo development	1
cell division	1
mitotic cell cycle phase transition	1
negative regulation of mitotic cell cycle	1
negative regulation of cell cycle phase transition	1
regulation of mitotic cell cycle phase transition	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPRA1	TRPA1	O75762	722
TPRA1	RSPRY1	Q96DX4	528
TPRA1	WDR25	Q64LD2	510
TPRA1	GPR107	Q5VW38	499
TPRA1	GPR108	Q9NPR9	476
TPRA1	CCDC106	Q9BWC9	475
TPRA1	FAM8A1	Q9UBU6	474
TPRA1	GPR161	Q8N6U8	467
TPRA1	NUDT13	Q86X67	464
TPRA1	ANKRD50	Q9ULJ7	462
TPRA1	ZC3H15	Q8WU90	458
TPRA1	TRPV1	Q8NER1	452
TPRA1	PDHA2	P29803	449
TPRA1	GPR157	Q5UAW9	449
TPRA1	RCBTB1	Q8NDN9	449

IntAct

6 interactions, top by confidence:

A	B	Type	Score
NLGN3	TPRA1	psi-mi:“MI:0915”(physical association)	0.460
TPRA1	NLGN3	psi-mi:“MI:0915”(physical association)	0.460
NLGN3	TPRA1	psi-mi:“MI:0403”(colocalization)	0.460
TPRA1	BMPR1B	psi-mi:“MI:0914”(association)	0.350
SLC9A6	GOLIM4	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): TPRA1 (Affinity Capture-Western), SLC6A8 (Affinity Capture-MS), MFSD8 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), BMPR1B (Affinity Capture-MS), TMEM143 (Affinity Capture-MS), SLC30A6 (Affinity Capture-MS), SNX13 (Affinity Capture-MS), TMEM63B (Affinity Capture-MS), DOLK (Affinity Capture-MS), SC5D (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), GHITM (Affinity Capture-MS), TMEM63A (Affinity Capture-MS)

ESM2 similar proteins: A2AF53, A4FV75, A4K2N5, A4K2W1, A5A6S6, A6QL84, A6ZIQ8, A9JRA0, B1AZA5, D3ZEH5, D3ZXD8, E1BD52, O60337, P58749, Q08DE2, Q108U3, Q2TBU2, Q3SYY9, Q3TMP8, Q4R5E3, Q58DA4, Q5BJW3, Q5JZQ8, Q5R8H8, Q5R9W1, Q5RBJ7, Q5RFE0, Q5ZII3, Q62302, Q6UWH6, Q6ZQ89, Q78S06, Q7SYC7, Q7ZUA6, Q86W33, Q8CIF6, Q8K0B2, Q8N2H4, Q8NBJ9, Q8NFB2

Diamond homologs: Q18936, Q4V8X0, Q5ZII3, Q60QP4, Q791F6, Q86W33, Q99MU1

SIGNOR signaling

0 interactions.

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	0
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1490 predictions. Top by Δscore:

Variant	Effect	Δscore
3:127573784:CCGAG:C	acceptor_gain	1.0000
3:127573785:CGAG:C	acceptor_gain	1.0000
3:127573785:CGAGC:C	acceptor_gain	1.0000
3:127573788:GCTGA:G	acceptor_loss	1.0000
3:127573789:C:CC	acceptor_gain	1.0000
3:127575180:CTCA:C	donor_loss	1.0000
3:127575181:TCACC:T	donor_loss	1.0000
3:127575182:CACC:C	donor_loss	1.0000
3:127575183:AC:A	donor_gain	1.0000
3:127575184:C:CG	donor_loss	1.0000
3:127575184:CC:C	donor_gain	1.0000
3:127575261:CACAG:C	acceptor_gain	1.0000
3:127575263:CAG:C	acceptor_gain	1.0000
3:127575264:AG:A	acceptor_gain	1.0000
3:127575266:C:CC	acceptor_gain	1.0000
3:127575399:GCACC:G	donor_loss	1.0000
3:127575400:CACCA:C	donor_loss	1.0000
3:127575401:A:AC	donor_gain	1.0000
3:127575401:A:AG	donor_loss	1.0000
3:127575402:C:CC	donor_gain	1.0000
3:127575502:CGAG:C	acceptor_gain	1.0000
3:127575503:GAGC:G	acceptor_loss	1.0000
3:127575504:AGC:A	acceptor_loss	1.0000
3:127575506:C:CC	acceptor_gain	1.0000
3:127575704:C:CA	donor_gain	1.0000
3:127575747:A:AC	donor_gain	1.0000
3:127575748:C:CC	donor_gain	1.0000
3:127575748:CAAGG:C	donor_gain	1.0000
3:127575935:CTCA:C	donor_loss	1.0000
3:127575936:TCACC:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019089 (3:127573484 T>A), RS1000198840 (3:127579055 G>A), RS1000239595 (3:127585869 G>A), RS1000345902 (3:127586192 T>C), RS1000436129 (3:127591644 G>C), RS1000487660 (3:127579622 T>C,G), RS1000492836 (3:127598352 A>C,G), RS1000562732 (3:127591554 G>A), RS1000609215 (3:127598172 G>T), RS1000710714 (3:127598816 A>C,G), RS1000728425 (3:127575703 T>C), RS1000760089 (3:127581757 C>A), RS1000933442 (3:127591809 C>T), RS1001022797 (3:127574655 G>A), RS1001082453 (3:127580898 G>A)

Disease associations

OMIM: gene MIM:608336 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST006190_62	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-08
GCST007323_21	Risk-taking tendency (4-domain principal component model)	1.000000e-08
GCST007325_141	General risk tolerance (MTAG)	2.000000e-12
GCST007325_87	General risk tolerance (MTAG)	1.000000e-09
GCST007326_107	Number of sexual partners	3.000000e-11
GCST009391_349	Metabolite levels	4.000000e-06
GCST010002_438	Refractive error	9.000000e-21
GCST010242_173	HDL cholesterol levels	2.000000e-11
GCST010244_422	Triglyceride levels	9.000000e-10
GCST012191_5	Body mass index and systolic blood pressure (bivariate analysis)	8.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008579	risk-taking behaviour
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Other non-GPCR 7TM proteins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	4
Benzo(a)pyrene	increases expression	3
Valproic Acid	affects cotreatment, decreases expression	2
Particulate Matter	increases expression	2
aristolochic acid I	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
gardiquimod	decreases expression, decreases reaction	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Smoke	increases expression	1
Sulindac	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0RX	Ubigene HeLa TPRA1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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