TBC1D5

Summary

TBC1D5 (TBC1 domain family member 5, HGNC:19166) is a protein-coding gene on chromosome 3p24.3, encoding TBC1 domain family member 5 (Q92609). May act as a GTPase-activating protein (GAP) for Rab family protein(s).

Enables AP-2 adaptor complex binding activity and retromer complex binding activity. Involved in several processes, including macroautophagy; positive regulation of receptor internalization; and retrograde transport, endosome to Golgi. Located in several cellular components, including Atg1/ULK1 kinase complex; autophagosome; and cytoplasmic vesicle membrane. Part of retromer complex.

Source: NCBI Gene 9779 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 131 total
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001349074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19166
Approved symbol	TBC1D5
Name	TBC1 domain family member 5
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0210
Ensembl gene	ENSG00000131374
Ensembl biotype	protein_coding
OMIM	615740
Entrez	9779

Gene structure

Transcript identifiers

Ensembl transcripts: 75 — 59 protein_coding, 13 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000253692, ENST00000412981, ENST00000414318, ENST00000414349, ENST00000415814, ENST00000423331, ENST00000425944, ENST00000428355, ENST00000429383, ENST00000429924, ENST00000430169, ENST00000433533, ENST00000434420, ENST00000443386, ENST00000443499, ENST00000444471, ENST00000444756, ENST00000445294, ENST00000446818, ENST00000446863, ENST00000452492, ENST00000465884, ENST00000471679, ENST00000473612, ENST00000480435, ENST00000481396, ENST00000485432, ENST00000486224, ENST00000497531, ENST00000507877, ENST00000696125, ENST00000907029, ENST00000907030, ENST00000907031, ENST00000907032, ENST00000907033, ENST00000907034, ENST00000907035, ENST00000907036, ENST00000907037, ENST00000907038, ENST00000907039, ENST00000907040, ENST00000907041, ENST00000907042, ENST00000907043, ENST00000907044, ENST00000907045, ENST00000907046, ENST00000907047, ENST00000907048, ENST00000907049, ENST00000907050, ENST00000907051, ENST00000907052, ENST00000907053, ENST00000965796, ENST00000965797, ENST00000965798, ENST00000965799, ENST00000965800, ENST00000965801, ENST00000965802, ENST00000965803, ENST00000965804, ENST00000965805, ENST00000965806, ENST00000965807, ENST00000965808, ENST00000965809, ENST00000965810, ENST00000965811, ENST00000965812, ENST00000965813, ENST00000965814

RefSeq mRNA: 21 — MANE Select: NM_001349074 NM_001134381, NM_001349073, NM_001349074, NM_001349075, NM_001349076, NM_001349077, NM_001349078, NM_001349079, NM_001349080, NM_001349081, NM_001349082, NM_001349083, NM_001349084, NM_001349085, NM_001349086, NM_001349087, NM_001349088, NM_001349089, NM_001349090, NM_001349091, NM_014744

CCDS: CCDS33714, CCDS46770

Canonical transcript exons

ENST00000696125 — 23 exons

Exon	Start	End
ENSE00000901404	17291895	17292001
ENSE00000901406	17372075	17372247
ENSE00000901407	17374471	17374540
ENSE00000901410	17383913	17384015
ENSE00000901411	17403181	17403248
ENSE00001426889	17623849	17623913
ENSE00001505881	17374629	17374679
ENSE00001505882	17376525	17376613
ENSE00003469545	17167749	17167828
ENSE00003489275	17307992	17308134
ENSE00003552263	17166767	17166928
ENSE00003559735	17428450	17428519
ENSE00003600604	17258506	17258591
ENSE00003603487	17238163	17238419
ENSE00003610187	17214207	17214370
ENSE00003623157	17406418	17406526
ENSE00003633277	17404694	17404768
ENSE00003675605	17404872	17404961
ENSE00003682375	17185109	17185208
ENSE00003799360	17508474	17508605
ENSE00003966080	17157168	17161256
ENSE00003966081	17742481	17742631
ENSE00003966082	17233685	17233750

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.16.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0968 / max 102.0991, expressed in 206 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41364	21.6980	1816
41397	1.0968	206
41398	0.7912	194
41365	0.0888	46
41363	0.0693	31
41362	0.0343	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.16	gold quality
corpus callosum	UBERON:0002336	94.36	gold quality
colonic epithelium	UBERON:0000397	93.94	gold quality
adrenal tissue	UBERON:0018303	93.92	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.90	gold quality
inferior olivary complex	UBERON:0002127	93.55	gold quality
trabecular bone tissue	UBERON:0002483	92.97	gold quality
adult organism	UBERON:0007023	92.97	gold quality
inferior vagus X ganglion	UBERON:0005363	92.77	gold quality
substantia nigra pars compacta	UBERON:0001965	92.67	gold quality
lateral globus pallidus	UBERON:0002476	92.62	gold quality
bone marrow cell	CL:0002092	92.43	gold quality
tendon	UBERON:0000043	92.36	gold quality
CA1 field of hippocampus	UBERON:0003881	92.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.13	gold quality
cranial nerve II	UBERON:0000941	92.09	gold quality
sural nerve	UBERON:0015488	92.03	gold quality
monocyte	CL:0000576	91.75	gold quality
mononuclear cell	CL:0000842	91.68	gold quality
cervix squamous epithelium	UBERON:0006922	91.67	silver quality
entorhinal cortex	UBERON:0002728	91.55	gold quality
islet of Langerhans	UBERON:0000006	91.46	gold quality
hair follicle	UBERON:0002073	91.39	silver quality
leukocyte	CL:0000738	91.38	gold quality
globus pallidus	UBERON:0001875	91.28	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.15	gold quality
parotid gland	UBERON:0001831	91.13	gold quality
medial globus pallidus	UBERON:0002477	91.12	gold quality
ventricular zone	UBERON:0003053	91.12	gold quality
corpus epididymis	UBERON:0004359	90.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	318.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

149 targeting TBC1D5, 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-3120-5P	100.00	65.56	965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6756-5P	99.82	67.97	2466

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• Membrane recruitment of the cargo-selective retromer subcomplex VPS35/29/26 is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. (PMID:19531583)
• TBC1D5 and the AP2 complex are important novel regulators of the rerouting of ATG9-containing vesicular carriers toward sites of autophagosome formation. (PMID:24603492)
• Data indicate that TBC1 domain family, member 5 protein (TBC1d5) interacts with retromer and the interaction is important for retromer-mediated receptor trafficking. (PMID:27827364)
• Single nucleotide polymorphisms in TBC1D5 show associations in Schizophrenia and general cognitive function. (PMID:28746715)
• RidL is critical for binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the regulator TBC1D5. (PMID:29146912)
• Control of RAB7 activity and localization through the retromer-TBC1D5 complex enables RAB7-dependent mitophagy. (PMID:29158324)
• TBC1D5 is a GAP for Rab7b in the control of endosomal transport to the trans-Golgi. (PMID:30111580)
• The secreted protein kinase CstK from Coxiella burnetii influences vacuole development and interacts with the GTPase-activating host protein TBC1D5. (PMID:32303638)
• TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry. (PMID:32521275)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d5	ENSDARG00000036212
mus_musculus	Tbc1d5	ENSMUSG00000023923
rattus_norvegicus	Tbc1d5	ENSRNOG00000010637

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), TBC1D15 (ENSG00000121749), 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 5 — Q92609 (reviewed: Q92609)

All UniProt accessions (14): B9A6K1, C9J397, C9J3F6, C9JDR8, C9JED7, C9JIU4, C9JMP7, C9JNM0, C9JW04, C9JWX0, C9K0P2, Q92609, F2Z3C3, F2Z3I5

UniProt curated annotations — full annotation on UniProt →

Function. May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity. Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy. May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes.

Subunit / interactions. Interacts with MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1, GABARAPL2. Interacts with VPS29 and VPS35; indicative for an association with retromer CSC subcomplex. MAP1LC3A and VPS29 compete for binding to TBC1D5. Interacts with AP2M1; indicative for an association with the AP2 complex. Interacts with ULK1 and ATG13 (phosphorylated); indicative for an association with the activated ULK1-ATG13-FIP200 complex. Interacts with ATG9A; the interactions seems to be restricted to the AP2-clathrin-associated fraction of ATG9A.

Subcellular location. Endosome membrane. Cytoplasmic vesicle. Autophagosome.

Domain organisation. The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab’s ‘switch 2’ glutamine and insert in Rab’s active site. The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. LIR 1 is also implicated in interaction with retromer; LIR 2 is only implicated in interaction with ATG8 family proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92609-1	1	yes
Q92609-2	2

RefSeq proteins (21): NP_001127853, NP_001336002, NP_001336003, NP_001336004, NP_001336005, NP_001336006, NP_001336007, NP_001336008, NP_001336009, NP_001336010, NP_001336011, NP_001336012, NP_001336013, NP_001336014, NP_001336015, NP_001336016, NP_001336017, NP_001336018, NP_001336019, NP_001336020, NP_055559 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily

Pfam: PF00566

UniProt features (38 total): modified residue 13, compositionally biased region 7, region of interest 5, mutagenesis site 3, site 2, short sequence motif 2, chain 1, domain 1, splice variant 1, sequence variant 1, turn 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5GTU	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92609-F1	66.31	0.36

Functional residue map

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

Catalytic / active sites (2): 169 (arginine finger); 204 (glutamine finger)

Post-translational modifications (13): 42, 43, 44, 460, 522, 539, 541, 544, 554, 570, 584, 730, 791

Mutagenesis-validated functional residues (3):

Position	Phenotype
59	disrupts interaction with vps29.
169	abolishes retromer displacement from endosome membrane; no effect on interaction with vps29; when associated with a-204.
204	abolishes retromer displacement from endosome membrane; no effect on interaction with vps29; when associated with a-169.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 236 (showing top): GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, AREB6_01, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, PATIL_LIVER_CANCER, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION, GOBP_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CILIUM_ORGANIZATION

GO Biological Process (6): positive regulation of receptor internalization (GO:0002092), autophagy (GO:0006914), protein transport (GO:0015031), macroautophagy (GO:0016236), retrograde transport, endosome to Golgi (GO:0042147), response to starvation (GO:0042594)

GO Molecular Function (5): GTPase activator activity (GO:0005096), AP-2 adaptor complex binding (GO:0035612), protein-containing complex binding (GO:0044877), retromer complex binding (GO:1905394), protein binding (GO:0005515)

GO Cellular Component (11): autophagosome (GO:0005776), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endosome membrane (GO:0010008), retromer complex (GO:0030904), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), AP-2 adaptor complex (GO:0030122), cytoplasmic vesicle (GO:0031410), Atg1/ULK1 kinase complex (GO:1990316)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
endomembrane system	3
cellular anatomical structure	3
protein-containing complex binding	2
binding	2
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
response to stress	1
response to nutrient levels	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
vacuole	1
intracellular membrane-bounded organelle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
membrane protein complex	1
intracellular anatomical structure	1
cytoplasmic vesicle	1
clathrin coat of endocytic vesicle	1
clathrin adaptor complex	1
clathrin coat of coated pit	1
plasma membrane protein complex	1
intracellular vesicle	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D5	VPS29	Q9UBQ0	985
TBC1D5	VPS26A	O75436	910
TBC1D5	GABARAPL2	P60520	880
TBC1D5	F5GZY7	F5GZY7	880
TBC1D5	VPS35	Q96QK1	874
TBC1D5	TBC1D15	Q8TC07	789
TBC1D5	SNX3	O60493	765
TBC1D5	SNX27	Q96L92	716
TBC1D5	FKBP15	Q5T1M5	709
TBC1D5	VPS26B	Q4G0F5	702
TBC1D5	RAB7A	P51149	695
TBC1D5	SNX5	Q9Y5X3	689
TBC1D5	SNX1	Q13596	651
TBC1D5	TBC1D25	Q3MII6	650
TBC1D5	TBC1D2	Q9BYX2	642

IntAct

152 interactions, top by confidence:

A	B	Type	Score
VPS35	VPS26A	psi-mi:“MI:0914”(association)	0.980
VPS29	TBC1D5	psi-mi:“MI:0915”(physical association)	0.860
VPS29	TBC1D5	psi-mi:“MI:0914”(association)	0.860
TBC1D5	VPS35	psi-mi:“MI:0915”(physical association)	0.860
VPS26A	TBC1D5	psi-mi:“MI:0914”(association)	0.810
TBC1D5	VPS26A	psi-mi:“MI:0914”(association)	0.810
TBC1D5	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.800
GABARAPL2	TBC1D5	psi-mi:“MI:0915”(physical association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
VPS29	CCDC22	psi-mi:“MI:0914”(association)	0.790
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
AP2M1	TBC1D5	psi-mi:“MI:0915”(physical association)	0.740
TBC1D5	AP2M1	psi-mi:“MI:0407”(direct interaction)	0.740
VPS29	VPS26B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TBC1D5	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
MAP1LC3B	TBC1D5	psi-mi:“MI:0407”(direct interaction)	0.570
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570

BioGRID (157): GABARAPL2 (Two-hybrid), GABARAPL1 (Two-hybrid), VPS29 (Two-hybrid), EIF1AD (Two-hybrid), TBC1D5 (Affinity Capture-MS), TBC1D5 (Affinity Capture-MS), GABARAPL2 (Two-hybrid), TBC1D5 (Two-hybrid), TBC1D5 (Affinity Capture-MS), TBC1D5 (Proximity Label-MS), TBC1D5 (Affinity Capture-MS), TBC1D5 (Affinity Capture-MS), TBC1D5 (Affinity Capture-MS), TBC1D5 (Proximity Label-MS), TBC1D5 (Affinity Capture-MS)

ESM2 similar proteins: A1CFB3, A2QNQ5, A6H8I2, A7ERM5, A7KAK6, A7KAN4, C8VDQ4, O43048, O43052, O59737, P09379, P17121, P20485, P35845, P48365, P48566, P53258, P87234, Q08484, Q09830, Q09844, Q12317, Q1DN93, Q1E145, Q2U0C3, Q3ZDQ4, Q4WHB7, Q4WID6, Q4WQJ1, Q5AW75, Q5B4C9, Q5BCU8, Q5BGR2, Q6BU76, Q6C7W0, Q6FWI1, Q755I4, Q7RX99, Q80XQ2, Q8R5A6

Diamond homologs: Q80XQ2, Q92609, A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A6H6A9, A6H8I2, A6NDS4, A6NER0, A6QP29, B0R0W9, B1AVH7, B5DFA1, B9A6J9, C8VDQ4, D2H0G5, H2KZZ6, O60343, O60447, O95759, O97790, P0C7X1, P35125, P58802, Q09830, Q0IIM8, Q2KI13, Q2M2D7, Q3UYK3, Q4KMP7, Q4QQU7, Q55EP9, Q5R372, Q5RAN1, Q5RCW6, Q5SVR0, Q5TC63, Q5ZJ17

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Activation of BAD and translocation to mitochondria	6	59.3×	5e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	52.4×	7e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	52.4×	7e-08
Activation of BH3-only proteins	6	38.7×	5e-07
RHO GTPases activate PKNs	6	24.7×	5e-06
Intrinsic Pathway for Apoptosis	6	22.8×	8e-06
Macroautophagy	12	18.0×	8e-10
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	16.0×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to phagophore assembly site	5	50.6×	6e-06
mitophagy	12	38.9×	1e-13
autophagosome assembly	11	25.2×	2e-10
autophagosome maturation	6	21.5×	4e-05
protein targeting	5	18.7×	4e-04
endocytic recycling	6	16.4×	2e-04
macroautophagy	6	14.7×	2e-04
retrograde transport, endosome to Golgi	7	14.7×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

8848 predictions. Top by Δscore:

Variant	Effect	Δscore
3:17166926:GATC:G	acceptor_loss	1.0000
3:17166927:ATCTA:A	acceptor_loss	1.0000
3:17166928:TC:T	acceptor_loss	1.0000
3:17166929:C:CA	acceptor_loss	1.0000
3:17166930:T:C	acceptor_loss	1.0000
3:17167744:CATA:C	donor_loss	1.0000
3:17167745:ATAC:A	donor_loss	1.0000
3:17167746:TACC:T	donor_loss	1.0000
3:17167747:A:AC	donor_gain	1.0000
3:17167747:ACCTG:A	donor_loss	1.0000
3:17167748:C:CA	donor_loss	1.0000
3:17167748:C:CC	donor_gain	1.0000
3:17167824:ATTTA:A	acceptor_gain	1.0000
3:17167825:TTTA:T	acceptor_gain	1.0000
3:17167826:TTA:T	acceptor_gain	1.0000
3:17167827:TA:T	acceptor_gain	1.0000
3:17167827:TACTG:T	acceptor_loss	1.0000
3:17167828:AC:A	acceptor_loss	1.0000
3:17167829:C:CA	acceptor_loss	1.0000
3:17167829:C:CC	acceptor_gain	1.0000
3:17167830:T:A	acceptor_loss	1.0000
3:17185103:ACTT:A	donor_loss	1.0000
3:17185104:CTTA:C	donor_loss	1.0000
3:17185105:TTAC:T	donor_loss	1.0000
3:17185106:TACC:T	donor_loss	1.0000
3:17185107:A:AC	donor_gain	1.0000
3:17185107:A:AG	donor_loss	1.0000
3:17185108:C:CC	donor_gain	1.0000
3:17185108:C:CG	donor_loss	1.0000
3:17185108:CCAAG:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000661 (3:17342619 C>T), RS1000011848 (3:17409394 C>T), RS1000012684 (3:17554099 TAAGA>T), RS1000015854 (3:17402561 T>C), RS1000017827 (3:17534269 T>C), RS1000020691 (3:17250521 A>C), RS1000021166 (3:17616151 T>C), RS1000024281 (3:17473447 C>T), RS1000030228 (3:17620020 G>A), RS1000031240 (3:17299584 T>C), RS1000060600 (3:17533857 C>A,G), RS1000066758 (3:17686807 A>C), RS1000077308 (3:17623328 CAA>C), RS1000077824 (3:17619717 A>G), RS1000079630 (3:17250600 C>A)

Disease associations

OMIM: gene MIM:615740 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST002539_46	Schizophrenia	5.000000e-09
GCST004286_2	Midgestational circulating levels of PBDEs (fetal genetic effect)	8.000000e-08
GCST004599_291	Mean platelet volume	4.000000e-18
GCST004603_221	Platelet count	2.000000e-25
GCST004607_255	Plateletcrit	5.000000e-13
GCST004616_140	Platelet distribution width	5.000000e-10
GCST004946_109	Schizophrenia	3.000000e-08
GCST006803_72	Schizophrenia	2.000000e-09
GCST006810_12	Self-reported risk-taking behaviour	5.000000e-09
GCST007325_43	General risk tolerance (MTAG)	5.000000e-08
GCST008163_400	Height	2.000000e-06
GCST010698_53	Subcortical volume (min-P)	2.000000e-10
GCST010699_99	Brain morphology (min-P)	7.000000e-12
GCST010701_127	Cortical surface area (MOSTest)	1.000000e-10
GCST010702_39	Subcortical volume (MOSTest)	2.000000e-10
GCST010703_225	Brain morphology (MOSTest)	8.000000e-13
GCST010991_7	Parkinson’s disease	9.000000e-09
GCST90000047_85	Age at first sexual intercourse	4.000000e-11
GCST90002381_139	Eosinophil count	3.000000e-12
GCST90002382_555	Eosinophil percentage of white cells	3.000000e-16
GCST90002395_367	Mean platelet volume	1.000000e-30
GCST90002400_353	Plateletcrit	2.000000e-31
GCST90002402_300	Platelet count	7.000000e-55
GCST90011899_57	Aspartate aminotransferase levels	1.000000e-08
GCST90093325_4	Language functional connectivity	7.000000e-16

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement
EFO:0007797	language measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067197 (SINGLE PROTEIN)

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

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
7.58	Kd	26.48	nM	CHEMBL5653589
7.58	ED50	26.48	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149551: Binding affinity to human TBC1D5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0265	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	5
sodium arsenite	increases reaction, decreases expression, increases abundance, affects binding	4
bisphenol A	decreases methylation, increases expression, increases methylation, affects cotreatment	3
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
tamibarotene	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Resveratrol	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Ethanol	increases expression	1
Arsenic	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	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
CHEMBL5652593	Binding	Binding affinity to human TBC1D5 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.