TBC1D3K

Summary

TBC1D3K (TBC1 domain family member 3K, HGNC:51245) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3K (A0A087X1G2). Acts as a GTPase activating protein for RAB5.

Predicted to enable GTPase activator activity. Predicted to be located in plasma membrane.

Source: NCBI Gene 101060351 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001291464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:51245
Approved symbol	TBC1D3K
Name	TBC1 domain family member 3K
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000273513
Ensembl biotype	protein_coding
Entrez	101060351

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000620247, ENST00000859823

RefSeq mRNA: 1 — MANE Select: NM_001291464 NM_001291464

CCDS: CCDS74042

Canonical transcript exons

ENST00000620247 — 14 exons

Exon	Start	End
ENSE00003714746	37925999	37926071
ENSE00003718862	37932355	37932420
ENSE00003721162	37933354	37933506
ENSE00003721663	37930450	37930498
ENSE00003725945	37929086	37929195
ENSE00003727598	37928649	37928756
ENSE00003729342	37928125	37928205
ENSE00003732792	37932884	37932983
ENSE00003736059	37924415	37924570
ENSE00003738981	37931042	37931162
ENSE00003739666	37931876	37931970
ENSE00003746506	37927603	37927642
ENSE00003751653	37926234	37926319
ENSE00003978224	37934488	37935371

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 98.02.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.02	gold quality
bone marrow cell	CL:0002092	54.92	silver quality
bone marrow	UBERON:0002371	46.13	gold quality
skeletal muscle tissue	UBERON:0001134	44.16	gold quality
muscle tissue	UBERON:0002385	42.26	gold quality
right uterine tube	UBERON:0001302	42.19	silver quality
duodenum	UBERON:0002114	42.03	gold quality
lymph node	UBERON:0000029	40.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	39.32	gold quality
blood	UBERON:0000178	38.70	gold quality
ganglionic eminence	UBERON:0004023	37.82	gold quality
smooth muscle tissue	UBERON:0001135	37.77	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
fundus of stomach	UBERON:0001160	36.24	gold quality
testis	UBERON:0000473	34.54	gold quality
cortex of kidney	UBERON:0001225	34.52	gold quality
right testis	UBERON:0004534	34.39	gold quality
right coronary artery	UBERON:0001625	34.35	gold quality
left testis	UBERON:0004533	33.43	gold quality
tonsil	UBERON:0002372	33.32	gold quality
metanephros cortex	UBERON:0010533	32.88	gold quality
kidney	UBERON:0002113	32.40	gold quality
liver	UBERON:0002107	32.34	gold quality
adult mammalian kidney	UBERON:0000082	32.05	gold quality
muscle of leg	UBERON:0001383	31.57	gold quality
primary visual cortex	UBERON:0002436	31.16	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
gastrocnemius	UBERON:0001388	30.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TBC1D3K, 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-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-548AD-3P	94.39	66.04	350

Cross-species orthologs

0 orthologs

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), 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), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 3K — A0A087X1G2 (reviewed: A0A087X1G2)

All UniProt accessions (1): A0A087X1G2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11.

Subcellular location. Cell membrane.

Post-translational modifications. Ubiquitinated by a CUL7-based E3 ligase, which leads to proteasomal degradation. Palmitoylation is required for membrane localization and protects TBC1D3 from ubiquitination.

Miscellaneous. TBC1D3 is encoded by a collection of very similar paralogs with multiple copies of each paralog, some human genomes encoding well over 50 copies depending on ethnic origin of the donor.

RefSeq proteins (1): NP_001278393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR050302	Rab_GAP_TBC_domain	Family

Pfam: PF00566

UniProt features (6 total): lipid moiety-binding region 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A087X1G2-F1	60.96	0.25

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 (2): 318, 325

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR335_3P, MIR5585_5P, chr17q12, JINESH_BLEBBISHIELD_VS_LIVE_CONTROL_UP, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME, GOCC_ENDOSOME, GOMF_GTPASE_ACTIVATOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (3): endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3K	KRTAP2-2	Q9BYT5	590
TBC1D3K	ERLN	P0DI80	571
TBC1D3K	C17orf50	Q8WW18	570
TBC1D3K	SCGB1C2	P0DMR2	542
TBC1D3K	KRTAP9-7	A8MTY7	526
TBC1D3K	CDRT15L2	A8MXV6	506
TBC1D3K	MTRNR2L1	P0CJ68	506
TBC1D3K	CFAP97D1	B2RV13	446
TBC1D3K	SPMAP1	A8MV24	434
TBC1D3K	KRTAP9-8	Q9BYQ0	432
TBC1D3K	SPEM2	Q0P670	419
TBC1D3K	OR1E2	P47887	418
TBC1D3K	CCDC144A	A2RUR9	402
TBC1D3K	SLC35G6	P0C7Q6	399
TBC1D3K	SLC35G3	Q8N808	398

IntAct

0 interactions, top by confidence:

BioGRID (5): TBC1D3K (Two-hybrid), TBC1D3K (Two-hybrid), TBC1D3K (Negative Genetic), TBC1D3K (Negative Genetic), TBC1D3K (Negative Genetic)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A6H6A9, A6NDS4, A6NER0, B9A6J9, H2KZZ6, P0C7X1, P35125, Q2M2D7, Q5RAN1, Q5SVR0, Q66K14, Q6DHY5, Q6IPX1, Q80XC3, Q86UD7, Q8IZP1, Q92738, Q9UFV1, Q9Y3P9, A3KGB4, A6QP29, B0R0W9, B7ZAP0, O60343, O60447, O95759, O97790, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2467 predictions. Top by Δscore:

Variant	Effect	Δscore
17:37928647:A:AG	acceptor_gain	1.0000
17:37928648:G:GA	acceptor_gain	1.0000
17:37929196:G:GG	donor_gain	1.0000
17:37932979:GCAGA:G	donor_gain	1.0000
17:37932982:GA:G	donor_gain	1.0000
17:37932982:GAGT:G	donor_loss	1.0000
17:37932983:AGTA:A	donor_loss	1.0000
17:37932984:G:GG	donor_gain	1.0000
17:37932984:GTAA:G	donor_loss	1.0000
17:37934487:GCC:G	acceptor_gain	1.0000
17:37924570:GGTG:G	donor_loss	0.9900
17:37924571:G:C	donor_loss	0.9900
17:37926315:GTACA:G	donor_gain	0.9900
17:37926320:G:GG	donor_gain	0.9900
17:37927601:A:AG	acceptor_gain	0.9900
17:37927602:G:GG	acceptor_gain	0.9900
17:37928644:CACA:C	acceptor_loss	0.9900
17:37928645:ACAGC:A	acceptor_loss	0.9900
17:37928646:CAGCT:C	acceptor_loss	0.9900
17:37928647:A:AT	acceptor_loss	0.9900
17:37928648:GCT:G	acceptor_gain	0.9900
17:37928648:GCTC:G	acceptor_gain	0.9900
17:37928752:ACCAG:A	donor_loss	0.9900
17:37928753:CCAG:C	donor_loss	0.9900
17:37928754:CAG:C	donor_loss	0.9900
17:37928755:AGGT:A	donor_loss	0.9900
17:37928756:GGTA:G	donor_loss	0.9900
17:37928757:GT:G	donor_loss	0.9900
17:37928758:T:A	donor_loss	0.9900
17:37929070:T:TA	acceptor_gain	0.9900

AlphaMissense

3579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:37931114:T:C	F207L	0.981
17:37931116:C:A	F207L	0.981
17:37931116:C:G	F207L	0.981
17:37932911:T:A	W286R	0.932
17:37932911:T:C	W286R	0.932
17:37928700:T:A	W111R	0.929
17:37928700:T:C	W111R	0.929
17:37931117:T:A	W208R	0.901
17:37931117:T:C	W208R	0.901
17:37929094:G:C	K132N	0.899
17:37929094:G:T	K132N	0.899
17:37931115:T:C	F207S	0.895
17:37928158:T:A	W78R	0.894
17:37928158:T:C	W78R	0.894
17:37928702:G:C	W111C	0.889
17:37928702:G:T	W111C	0.889
17:37931119:G:C	W208C	0.888
17:37931119:G:T	W208C	0.888
17:37931111:G:C	A206P	0.879
17:37929173:T:C	F159L	0.877
17:37929175:C:A	F159L	0.877
17:37929175:C:G	F159L	0.877
17:37928160:G:C	W78C	0.869
17:37928160:G:T	W78C	0.869
17:37928752:A:C	Y128S	0.862
17:37928157:G:C	K77N	0.860
17:37928157:G:T	K77N	0.860
17:37928181:G:C	W85C	0.854
17:37928181:G:T	W85C	0.854
17:37928751:T:G	Y128D	0.854

dbSNP variants (sampled 300 via entrez): RS1157054647 (17:37930915 C>T), RS1157917450 (17:37932837 C>A,T), RS1158264303 (17:37921811 C>A), RS1158392012 (17:37930240 G>T), RS1158401122 (17:37924612 G>A), RS1158497970 (17:37923616 C>G,T), RS1159100165 (17:37930891 T>A,C), RS1159153691 (17:37923200 G>C), RS1159198773 (17:37929448 A>G), RS1159379071 (17:37922397 T>C), RS1160546016 (17:37933463 T>C), RS1161108855 (17:37921640 T>A), RS1161436582 (17:37923291 G>C), RS1162485563 (17:37924358 GA>G), RS1162903966 (17:37929646 A>G)

Disease associations

OMIM: gene `` | 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: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
tri-o-cresyl phosphate	increases expression	1
2-palmitoylglycerol	increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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