TBC1D15

Summary

TBC1D15 (TBC1 domain family member 15, HGNC:25694) is a protein-coding gene on chromosome 12q21.1, encoding TBC1 domain family member 15 (Q8TC07). Acts as a GTPase activating protein for RAB7A.

This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 64786 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 111 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001146213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25694
Approved symbol	TBC1D15
Name	TBC1 domain family member 15
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12085, DKFZp761D0223
Ensembl gene	ENSG00000121749
Ensembl biotype	protein_coding
OMIM	612662
Entrez	64786

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000319106, ENST00000460818, ENST00000462788, ENST00000468049, ENST00000472611, ENST00000474468, ENST00000479971, ENST00000482439, ENST00000483828, ENST00000485960, ENST00000491063, ENST00000498482, ENST00000546450, ENST00000546932, ENST00000548679, ENST00000549402, ENST00000550746, ENST00000867020, ENST00000867021, ENST00000867022, ENST00000867023, ENST00000867025, ENST00000867026, ENST00000867028, ENST00000867029, ENST00000921410, ENST00000921411, ENST00000921412

RefSeq mRNA: 10 — MANE Select: NM_001146213 NM_001146213, NM_001146214, NM_001385848, NM_001385849, NM_001385850, NM_001385851, NM_001385852, NM_001385853, NM_001385854, NM_022771

CCDS: CCDS31858, CCDS53814

Canonical transcript exons

ENST00000485960 — 17 exons

Exon	Start	End
ENSE00001883556	71922983	71924313
ENSE00003460324	71894686	71894883
ENSE00003466375	71920731	71920847
ENSE00003478400	71872929	71873003
ENSE00003504975	71918451	71918548
ENSE00003510277	71880469	71880607
ENSE00003531007	71907022	71907138
ENSE00003546998	71917698	71917797
ENSE00003561062	71839759	71839811
ENSE00003563165	71897847	71897941
ENSE00003567972	71921368	71921454
ENSE00003611872	71913826	71913926
ENSE00003662515	71895947	71896075
ENSE00003665827	71872070	71872168
ENSE00003687023	71896677	71896780
ENSE00003688818	71884811	71885021
ENSE00003791645	71893222	71893324

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5192 / max 889.9241, expressed in 1794 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126834	35.4478	1794
206802	0.0648	21
126838	0.0066	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.55	gold quality
body of pancreas	UBERON:0001150	95.13	gold quality
right lung	UBERON:0002167	94.83	gold quality
omental fat pad	UBERON:0010414	93.73	gold quality
peritoneum	UBERON:0002358	93.71	gold quality
gastrocnemius	UBERON:0001388	93.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.38	gold quality
ventricular zone	UBERON:0003053	93.28	gold quality
pericardium	UBERON:0002407	93.25	gold quality
tibial nerve	UBERON:0001323	93.21	gold quality
monocyte	CL:0000576	93.18	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.17	gold quality
mononuclear cell	CL:0000842	93.10	gold quality
gall bladder	UBERON:0002110	93.01	gold quality
adrenal tissue	UBERON:0018303	92.94	gold quality
stromal cell of endometrium	CL:0002255	92.90	gold quality
corpus callosum	UBERON:0002336	92.89	gold quality
endocervix	UBERON:0000458	92.86	gold quality
leukocyte	CL:0000738	92.85	gold quality
tibial artery	UBERON:0007610	92.83	gold quality
popliteal artery	UBERON:0002250	92.82	gold quality
upper lobe of left lung	UBERON:0008952	92.82	gold quality
colonic epithelium	UBERON:0000397	92.74	gold quality
pancreas	UBERON:0001264	92.71	gold quality
right adrenal gland cortex	UBERON:0035827	92.71	gold quality
left ovary	UBERON:0002119	92.68	gold quality
ectocervix	UBERON:0012249	92.61	gold quality
muscle of leg	UBERON:0001383	92.52	gold quality
left adrenal gland	UBERON:0001234	92.44	gold quality
adrenal gland	UBERON:0002369	92.44	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	346.79
E-MTAB-10283	no	295.07
E-CURD-53	no	238.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting TBC1D15, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 11)

• This paper primarily describes mouse TBC1D15 but also reports the primary structure of human TBC1D15. (PMID:16055087)
• although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence (PMID:20363736)
• Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology. (PMID:23077178)
• TBC1D15 is required for the accumulation of RhoA. (PMID:24337944)
• Demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. (PMID:24569479)
• Report provides evidence for a new function of TBC1D15 in the control of GLUT4 vesicles translocation through regulating Rab7 activity. Glucose uptake was greatly reduced when TBC1D15 was knocked out. (PMID:30316925)
• Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. (PMID:31664461)
• IFNB/interferon-beta regulates autophagy via a MIR1-TBC1D15-RAB7 pathway. (PMID:31958036)
• p53 destabilizing protein skews asymmetric division and enhances NOTCH activation to direct self-renewal of TICs. (PMID:32555153)
• A conserved, noncanonical insert in FIS1 mediates TBC1D15 and DRP1 recruitment for mitochondrial fission. (PMID:37777154)
• NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells. (PMID:38409448)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d15	ENSDARG00000057218
mus_musculus	Tbc1d15	ENSMUSG00000020130
rattus_norvegicus	Tbc1d15	ENSRNOG00000003889

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), EVI5L (ENSG00000142459), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), SGSM1 (ENSG00000167037), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 15 — Q8TC07 (reviewed: Q8TC07)

Alternative names: GTPase-activating protein RAB7

All UniProt accessions (7): C9JA93, Q8TC07, F8VV61, F8WAX5, F8WCB5, F8WDJ1, F8WF35

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6.

Subunit / interactions. Interacts with non-phosphorylated form of RAB8A; phosphorylation of RAB8A at ‘Thr-72’ disrupts this interaction. Interacts with ARMC12.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TC07-1	1	yes
Q8TC07-2	2
Q8TC07-3	3

RefSeq proteins (10): NP_001139685, NP_001139686, NP_001372777, NP_001372778, NP_001372779, NP_001372780, NP_001372781, NP_001372782, NP_001372783, NP_073608 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR021935	SGSM1/2_RBD	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily

Pfam: PF00566, PF12068

UniProt features (20 total): modified residue 10, sequence conflict 5, splice variant 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC07-F1	71.87	0.46

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 (10): 689, 205, 213, 2, 23, 70, 205, 274, 640, 675

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 181 (showing top): TAATAAT_MIR126, TTTGTAG_MIR520D, GOBP_REGULATION_OF_GTPASE_ACTIVITY, TGACCTY_ERR1_Q2, ATGCAGT_MIR217, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, chr12q21, GOBP_CILIUM_ORGANIZATION, ACATTCC_MIR1_MIR206, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5

GO Biological Process (1): regulation of GTPase activity (GO:0043087)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
cellular anatomical structure	2
regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D15	FIS1	Q9Y3D6	994
TBC1D15	TBC1D17	Q9HA65	804
TBC1D15	TBC1D5	Q92609	789
TBC1D15	GABARAPL2	P60520	788
TBC1D15	F5GZY7	F5GZY7	788
TBC1D15	RAB6A	P20340	756
TBC1D15	RAB4A	P20338	754
TBC1D15	RAB11A	P24410	742
TBC1D15	RAB7A	P51149	742
TBC1D15	TBC1D2	Q9BYX2	696
TBC1D15	CDC16	Q13042	679
TBC1D15	VAMP2	P19065	636
TBC1D15	RAB5A	P20339	623
TBC1D15	UBXN8	O00124	603
TBC1D15	RAB9A	P51151	598

IntAct

174 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
CAMLG	GET3	psi-mi:“MI:0914”(association)	0.820
OPTN	TBC1D15	psi-mi:“MI:0915”(physical association)	0.810
TBC1D15	OPTN	psi-mi:“MI:0915”(physical association)	0.810
CCNH	ERCC2	psi-mi:“MI:0914”(association)	0.750
CEP63	TBC1D15	psi-mi:“MI:0915”(physical association)	0.740
TBC1D15	CEP63	psi-mi:“MI:0915”(physical association)	0.740
KIF22	KPNA3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
GABARAP	TBC1D15	psi-mi:“MI:0407”(direct interaction)	0.590
TBC1D15	GABARAP	psi-mi:“MI:0915”(physical association)	0.590
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
CALCOCO1	TBC1D15	psi-mi:“MI:0915”(physical association)	0.560
TBC1D15	CEP63	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP1	TBC1D15	psi-mi:“MI:0915”(physical association)	0.560
GABARAPL1	TBC1D15	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (248): TBC1D15 (Two-hybrid), TBC1D15 (Two-hybrid), CEP63 (Two-hybrid), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: A1A5B6, O43147, P09379, P48365, Q2NKQ1, Q3MII6, Q6FWI1, Q80U12, Q8BPQ7, Q8BYH7, Q8TBP0, Q8TC07, Q94BY9, Q9CXF4, Q9HA65, Q9UUH7, I2HAA0, Q09830, Q6BU76, Q6GLZ0, Q28CB1, Q8R3D1, Q9NVG8, P48566, Q12344, O95759, O97790, Q5ZJ17, Q60949, Q86TI0, Q8BYJ6, Q9D9D3, Q9Z1A9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Lysosphingolipid and LPA receptors	5	30.7×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	6	12.8×	2e-03
mitophagy	6	11.6×	3e-03
macroautophagy	7	10.2×	2e-03
autophagosome assembly	7	9.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	71
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340527	GRCh37/hg19 12q15-21.2(chr12:70084476-77065764)x1	Pathogenic

SpliceAI

3285 predictions. Top by Δscore:

Variant	Effect	Δscore
12:71872062:T:TA	acceptor_gain	1.0000
12:71872065:TTTAG:T	acceptor_loss	1.0000
12:71872067:TAG:T	acceptor_loss	1.0000
12:71872068:A:AG	acceptor_gain	1.0000
12:71872068:AGA:A	acceptor_loss	1.0000
12:71872069:G:GT	acceptor_gain	1.0000
12:71872069:GA:G	acceptor_gain	1.0000
12:71872069:GAT:G	acceptor_gain	1.0000
12:71872069:GATT:G	acceptor_gain	1.0000
12:71872069:GATTA:G	acceptor_gain	1.0000
12:71872164:AAAAG:A	donor_gain	1.0000
12:71872165:AAAG:A	donor_gain	1.0000
12:71872166:AAG:A	donor_gain	1.0000
12:71872166:AAGGT:A	donor_loss	1.0000
12:71872167:AG:A	donor_gain	1.0000
12:71872167:AGGT:A	donor_loss	1.0000
12:71872168:GG:G	donor_gain	1.0000
12:71872169:G:GG	donor_gain	1.0000
12:71893220:A:AG	acceptor_gain	1.0000
12:71893221:G:GG	acceptor_gain	1.0000
12:71893325:G:GG	donor_gain	1.0000
12:71894677:A:AG	acceptor_gain	1.0000
12:71894679:T:A	acceptor_gain	1.0000
12:71894682:A:AG	acceptor_gain	1.0000
12:71894682:ATAGA:A	acceptor_loss	1.0000
12:71894683:T:G	acceptor_gain	1.0000
12:71894683:TA:T	acceptor_loss	1.0000
12:71894684:A:AG	acceptor_gain	1.0000
12:71894685:G:GG	acceptor_gain	1.0000
12:71894685:GA:G	acceptor_gain	1.0000

AlphaMissense

4491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:71896707:T:A	W356R	1.000
12:71896707:T:C	W356R	1.000
12:71897875:T:A	W390R	1.000
12:71897875:T:C	W390R	1.000
12:71907106:T:G	L440W	1.000
12:71913843:A:C	S457R	1.000
12:71913845:T:A	S457R	1.000
12:71913845:T:G	S457R	1.000
12:71918483:T:C	F529L	1.000
12:71918485:C:A	F529L	1.000
12:71918485:C:G	F529L	1.000
12:71918487:G:T	R530M	1.000
12:71918489:T:A	W531R	1.000
12:71918489:T:C	W531R	1.000
12:71918508:A:T	K537I	1.000
12:71918509:A:C	K537N	1.000
12:71918509:A:T	K537N	1.000
12:71918543:T:A	W549R	1.000
12:71918543:T:C	W549R	1.000
12:71894866:T:C	F297L	0.999
12:71894868:T:A	F297L	0.999
12:71894868:T:G	F297L	0.999
12:71896696:G:C	R352T	0.999
12:71896697:A:C	R352S	0.999
12:71896697:A:T	R352S	0.999
12:71897854:T:C	Y383H	0.999
12:71897854:T:G	Y383D	0.999
12:71897855:A:C	Y383S	0.999
12:71897866:A:G	K387E	0.999
12:71897868:A:C	K387N	0.999

dbSNP variants (sampled 300 via entrez): RS1000005445 (12:71860157 G>T), RS1000018954 (12:71845450 A>G), RS1000025877 (12:71890709 A>C), RS1000091078 (12:71923282 T>A), RS1000106065 (12:71855346 G>A,T), RS1000120861 (12:71904366 G>A), RS1000210557 (12:71866113 G>A,C), RS1000224590 (12:71859914 C>T), RS1000260830 (12:71909858 A>G), RS1000301072 (12:71845157 T>C), RS1000323720 (12:71854413 T>C), RS1000325751 (12:71856744 C>T), RS1000356396 (12:71886340 T>G), RS1000362037 (12:71871990 A>C), RS1000478204 (12:71872314 A>G)

Disease associations

OMIM: gene MIM:612662 | 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
GCST009184_10	Inferior parietal cortex volume	5.000000e-06
GCST009391_468	Metabolite levels	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295905 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — RAS subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NVP-BHG712	Binding	6.2	pKd

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.21	Kd	624	nM	CHEMBL3752910
6.08	ED50	828.6	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 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	2149550: Binding affinity to human TBC1D15 incubated for 45 mins by Kinobead based pull down assay	kd	0.6240	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, decreases methylation	5
sodium arsenite	increases reaction, increases abundance, increases expression, affects binding	3
Tobacco Smoke Pollution	increases expression	3
Cyclosporine	increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases 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
dorsomorphin	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118707	Binding	Binding affinity to TBC1D15 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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