PTAR1

Summary

PTAR1 (protein prenyltransferase alpha subunit repeat containing 1, HGNC:30449) is a protein-coding gene on chromosome 9q21.12, encoding Protein prenyltransferase alpha subunit repeat-containing protein 1 (Q7Z6K3). Substrate-recognition subunit of the geranylgeranyl transferase type 3 (GGTase-3) complex. It is a selective cancer dependency (DepMap: 24.3% of cell lines).

Predicted to enable protein prenyltransferase activity. Predicted to contribute to Rab geranylgeranyltransferase activity. Located in mitochondrion.

Source: NCBI Gene 375743 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 24.3% of screened cell lines
• MANE Select transcript: NM_001099666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30449
Approved symbol	PTAR1
Name	protein prenyltransferase alpha subunit repeat containing 1
Location	9q21.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188647
Ensembl biotype	protein_coding
OMIM	621024
Entrez	375743

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000340434, ENST00000377200, ENST00000415701, ENST00000467511, ENST00000472967, ENST00000474925, ENST00000912951

RefSeq mRNA: 7 — MANE Select: NM_001099666 NM_001099666, NM_001366935, NM_001366936, NM_001366937, NM_001366938, NM_001366939, NM_001366940

CCDS: CCDS47978, CCDS94417

Canonical transcript exons

ENST00000340434 — 8 exons

Exon	Start	End
ENSE00001365246	69734150	69734254
ENSE00001365441	69718650	69718684
ENSE00001370415	69741792	69741858
ENSE00001372424	69732139	69732352
ENSE00001606053	69723326	69723630
ENSE00001752399	69759853	69760011
ENSE00002211660	69709525	69718568
ENSE00003515113	69750781	69750950

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5084 / max 201.2631, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100823	19.2998	1789
100824	6.1893	1701
100825	1.2458	845
100822	0.5037	178
100826	0.2697	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.34	gold quality
epithelial cell of pancreas	CL:0000083	97.04	gold quality
endothelial cell	CL:0000115	96.55	gold quality
oviduct epithelium	UBERON:0004804	95.31	gold quality
kidney epithelium	UBERON:0004819	95.04	gold quality
ileal mucosa	UBERON:0000331	94.00	gold quality
tibialis anterior	UBERON:0001385	93.64	gold quality
cartilage tissue	UBERON:0002418	93.50	gold quality
upper arm skin	UBERON:0004263	93.38	gold quality
pancreatic ductal cell	CL:0002079	93.18	gold quality
visceral pleura	UBERON:0002401	93.09	gold quality
deltoid	UBERON:0001476	92.57	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.51	gold quality
corpus callosum	UBERON:0002336	92.40	gold quality
trabecular bone tissue	UBERON:0002483	92.40	gold quality
caput epididymis	UBERON:0004358	92.17	gold quality
calcaneal tendon	UBERON:0003701	92.11	gold quality
tibia	UBERON:0000979	91.89	gold quality
parietal pleura	UBERON:0002400	91.55	gold quality
bone marrow cell	CL:0002092	91.06	gold quality
renal medulla	UBERON:0000362	91.02	gold quality
bone marrow	UBERON:0002371	90.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.48	gold quality
adrenal tissue	UBERON:0018303	90.43	gold quality
cauda epididymis	UBERON:0004360	90.38	gold quality
seminal vesicle	UBERON:0000998	90.36	gold quality
trigeminal ganglion	UBERON:0001675	90.24	gold quality
dorsal root ganglion	UBERON:0000044	89.99	gold quality
pigmented layer of retina	UBERON:0001782	89.84	gold quality
corpus epididymis	UBERON:0004359	89.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

432 targeting PTAR1, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• This study reports the identification of a previously unknown human prenyltransferase complex consisting of an orphan prenyltransferase alpha subunit, PTAR1, and the catalytic beta-subunit of GGTase2, RabGGTB. (PMID:31209342)
• A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. (PMID:32128853)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptar1	ENSDARG00000102338
mus_musculus	Ptar1	ENSMUSG00000074925
rattus_norvegicus	Ptar1	ENSRNOG00000014891
drosophila_melanogaster	temp	FBGN0027296

Paralogs (2): RABGGTA (ENSG00000100949), FNTA (ENSG00000168522)

Protein

Protein identifiers

Protein prenyltransferase alpha subunit repeat-containing protein 1 — Q7Z6K3 (reviewed: Q7Z6K3)

All UniProt accessions (4): F5GXY1, J3KQP8, Q7Z6K3, X6R9N0

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition subunit of the geranylgeranyl transferase type 3 (GGTase-3) complex. The GGTase-3 complex geranylgeranylates and targets FBXL2 to the cellular membranes, where FBXL2 forms part of the E3 ubiquitin-protein ligase complex SCF(FBXL2) that mediates the degradation of membrane-anchored proteins. The GGTase-3 complex geranylgeranylates Golgi v-SNARE protein YKT6 at ‘Cys-194’ and this prenylation is required for Golgi SNARE complex assembly.

Subunit / interactions. Part of the GGTase-3 complex, composed of PTAR1 and RABGGTB; this complex geranylgeranylates FBXL2 and YKT6.

Similarity. Belongs to the protein prenyltransferase subunit alpha family.

RefSeq proteins (7): NP_001093136, NP_001353864, NP_001353865, NP_001353866, NP_001353867, NP_001353868, NP_001353869 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002088	Prenyl_trans_a	Repeat

Pfam: PF01239

Enzyme classification (BRENDA):

• EC 2.5.1.60 — protein geranylgeranyltransferase type II (BRENDA: 9 organisms, 44 substrates, 88 inhibitors, 7 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GERANYLGERANYL DIPHOSPHATE	—	2
RAB3A	—	1
YPT1P	0.0011	1
RAB PROTEIN	—	0

UniProt features (39 total): helix 15, mutagenesis site 6, repeat 6, strand 5, turn 3, initiator methionine 1, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6O60	X-RAY DIFFRACTION	2.5
6J7X	X-RAY DIFFRACTION	2.75
6J7F	X-RAY DIFFRACTION	2.88
6J6X	X-RAY DIFFRACTION	2.96
6J74	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6K3-F1	84.64	0.70

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 (1): 2

Mutagenesis-validated functional residues (6):

Position	Phenotype
31	impairs geranylgeranylation of ykt6.
35	impairs geranylgeranylation of ykt6. abolishes geranylgeranylation of ykt6; when associated with a-306.
48	impairs geranylgeranylation of ykt6. abolishes geranylgeranylation of ykt6; when associated with a-50 and a-306.
50	impairs geranylgeranylation of ykt6. abolishes geranylgeranylation of ykt6; when associated with a-48 and a-306.
232	impairs geranylgeranylation of ykt6.
306	impairs geranylgeranylation of ykt6. abolishes geranylgeranylation of ykt6; when associated with a-35. abolishes geranyl

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CUI_TCF21_TARGETS_2_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, chr9q21, GOMF_PRENYLTRANSFERASE_ACTIVITY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, WHITFIELD_CELL_CYCLE_S, GABRIELY_MIR21_TARGETS, PILON_KLF1_TARGETS_UP, JOHNSTONE_PARVB_TARGETS_2_DN, GOMF_PROTEIN_PRENYLTRANSFERASE_ACTIVITY, GCM_RAB10, CHAF1B_TARGET_GENES, CIITA_TARGET_GENES, E2F5_TARGET_GENES

GO Biological Process (1): protein prenylation (GO:0018342)

GO Molecular Function (4): protein prenyltransferase activity (GO:0008318), prenyltransferase activity (GO:0004659), Rab geranylgeranyltransferase activity (GO:0004663), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification process	1
prenylation	1
prenyltransferase activity	1
catalytic activity, acting on a protein	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein geranylgeranyltransferase activity	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTAR1	RABGGTB	P53611	820
PTAR1	ZKSCAN8	Q15776	506
PTAR1	FNTA	P49354	480
PTAR1	ZBTB41	Q5SVQ8	440
PTAR1	UNC50	Q53HI1	428
PTAR1	FBXL17	Q9UF56	420
PTAR1	GOLGA8J	A6NMD2	399
PTAR1	FBXL15	Q9H469	390
PTAR1	SACS	Q9NZJ4	382
PTAR1	FBXL2	Q9UKC9	372
PTAR1	C7orf25	Q9BPX7	369
PTAR1	PIP5K1B	P78518	367
PTAR1	GPBP1L1	Q9HC44	353
PTAR1	VARS1	P26640	351
PTAR1	METTL26	Q96S19	348

IntAct

56 interactions, top by confidence:

A	B	Type	Score
PTAR1	RABGGTB	psi-mi:“MI:0914”(association)	0.920
PTAR1	RABGGTB	psi-mi:“MI:0915”(physical association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0914”(association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0915”(physical association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0407”(direct interaction)	0.920
FBXL2	SKP1	psi-mi:“MI:0915”(physical association)	0.900
FBXL2	SKP1	psi-mi:“MI:0914”(association)	0.900
EXOSC1	EXOSC10	psi-mi:“MI:0914”(association)	0.810
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
RABGGTB	YKT6	psi-mi:“MI:0915”(physical association)	0.740
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
YKT6	C1QL1	psi-mi:“MI:0914”(association)	0.530
YKT6	NAPA	psi-mi:“MI:0914”(association)	0.530
SKP1	RABGGTB	psi-mi:“MI:0915”(physical association)	0.520
FBXL2	RABGGTB	psi-mi:“MI:0914”(association)	0.500
PTAR1	FBXL2	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (98): PTAR1 (Affinity Capture-MS), PTAR1 (Proximity Label-MS), PTAR1 (Affinity Capture-MS), PTAR1 (Affinity Capture-MS), PTAR1 (Affinity Capture-MS), CNIH1 (Synthetic Lethality), COL4A3BP (Synthetic Lethality), EXOC2 (Synthetic Lethality), EXOC4 (Synthetic Lethality), FBXO8 (Synthetic Lethality), IST1 (Synthetic Lethality), MARCH6 (Synthetic Lethality), NAA30 (Synthetic Lethality), PI4KB (Synthetic Lethality), PIKFYVE (Synthetic Lethality)

ESM2 similar proteins: O60939, P01134, P08887, P23510, P25291, P26012, P48030, P51641, P54900, P55259, P78380, Q07212, Q08E08, Q1A730, Q29108, Q2KHT6, Q3SXP7, Q56A07, Q58DF9, Q5H8A4, Q5M7U7, Q5SQ64, Q5ZMH6, Q62522, Q6MG56, Q7M729, Q7M730, Q7YR73, Q7Z6K3, Q864L3, Q86WI3, Q8BHK2, Q8C525, Q8IWT1, Q8R092, Q8TBF5, Q8VE33, Q95K48, Q969P5, Q96IK5

Diamond homologs: A1L3L1, A3KPW7, Q0IHB3, Q7Z6K3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1462 predictions. Top by Δscore:

Variant	Effect	Δscore
9:69732362:CAGCA:C	acceptor_gain	1.0000
9:69732366:A:C	acceptor_gain	1.0000
9:69732368:G:C	acceptor_gain	1.0000
9:69734144:CCACA:C	donor_loss	1.0000
9:69734145:CACAC:C	donor_loss	1.0000
9:69734146:ACACC:A	donor_loss	1.0000
9:69734147:CACC:C	donor_loss	1.0000
9:69734148:ACC:A	donor_loss	1.0000
9:69734149:C:A	donor_loss	1.0000
9:69734250:CTTTC:C	acceptor_gain	1.0000
9:69741859:C:CC	acceptor_gain	1.0000
9:69750957:A:AC	acceptor_gain	1.0000
9:69750966:A:C	acceptor_gain	1.0000
9:69759848:CTCA:C	donor_loss	1.0000
9:69759849:TCACA:T	donor_loss	1.0000
9:69759850:CA:C	donor_loss	1.0000
9:69759851:A:AC	donor_gain	1.0000
9:69759852:C:CT	donor_gain	1.0000
9:69759852:CA:C	donor_gain	1.0000
9:69759852:CAT:C	donor_gain	1.0000
9:69759852:CATG:C	donor_gain	1.0000
9:69759852:CATGT:C	donor_gain	1.0000
9:69759866:T:TA	donor_gain	1.0000
9:69718685:C:CC	acceptor_gain	0.9900
9:69732365:CA:C	acceptor_gain	0.9900
9:69732366:A:AC	acceptor_gain	0.9900
9:69732368:G:GC	acceptor_gain	0.9900
9:69734251:TTTC:T	acceptor_gain	0.9900
9:69734252:TTC:T	acceptor_gain	0.9900
9:69734253:TC:T	acceptor_gain	0.9900

AlphaMissense

2643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:69723336:A:G	W313R	1.000
9:69723336:A:T	W313R	1.000
9:69723581:A:T	V231D	1.000
9:69732179:C:G	R201P	1.000
9:69732189:A:G	W198R	1.000
9:69732189:A:T	W198R	1.000
9:69732191:G:T	A197D	1.000
9:69732198:A:G	Y195H	1.000
9:69732199:G:C	N194K	1.000
9:69732199:G:T	N194K	1.000
9:69732350:C:G	R144P	1.000
9:69732352:C:A	R143S	1.000
9:69732352:C:G	R143S	1.000
9:69734150:C:A	R143M	1.000
9:69734150:C:G	R143T	1.000
9:69734158:C:A	W140C	1.000
9:69734158:C:G	W140C	1.000
9:69734160:A:G	W140R	1.000
9:69734160:A:T	W140R	1.000
9:69734170:A:C	S136R	1.000
9:69734170:A:T	S136R	1.000
9:69734172:T:G	S136R	1.000
9:69734173:C:A	K135N	1.000
9:69734173:C:G	K135N	1.000
9:69734175:T:C	K135E	1.000
9:69734246:A:G	L111P	1.000
9:69734251:T:A	K109N	1.000
9:69734251:T:G	K109N	1.000
9:69734252:T:A	K109I	1.000
9:69734254:C:A	R108S	1.000

dbSNP variants (sampled 300 via entrez): RS1000158507 (9:69744486 A>C), RS1000269438 (9:69736529 C>T), RS1000346861 (9:69740430 G>A), RS1000399498 (9:69730871 G>A), RS1000454395 (9:69749383 T>C), RS1000504442 (9:69744794 T>C), RS1000545825 (9:69739633 C>G), RS1000659430 (9:69737626 T>G), RS1000725671 (9:69736378 G>A), RS1000736795 (9:69732197 T>C), RS1000763684 (9:69746229 A>G), RS1000915149 (9:69752313 T>C,G), RS1000991051 (9:69710704 T>C), RS1001001799 (9:69717317 A>G), RS1001010479 (9:69737865 G>A)

Disease associations

OMIM: gene MIM:621024 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066326 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.81	Kd	15.48	nM	CHEMBL3752910
7.81	ED50	15.52	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149140: Binding affinity to human PTAR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0155	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Camptothecin	decreases response to substance	1
Doxorubicin	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Vanadates	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
CHEMBL5652182	Binding	Binding affinity to human PTAR1 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TH39	HAP1 PTAR1 (-) 1	Cancer cell line	Male
CVCL_TH40	HAP1 PTAR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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