TBC1D3L

Summary

TBC1D3L (TBC1 domain family member 3L, HGNC:51246) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3L (B9A6J9). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 101060376 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001369500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:51246
Approved symbol	TBC1D3L
Name	TBC1 domain family member 3L
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274512
Ensembl biotype	protein_coding
Entrez	101060376

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000612727, ENST00000617678, ENST00000851784, ENST00000851785, ENST00000851786

RefSeq mRNA: 4 — MANE Select: NM_001369500 NM_001291459, NM_001369499, NM_001369500, NM_001369501

CCDS: CCDS74043

Canonical transcript exons

ENST00000612727 — 13 exons

Exon	Start	End
ENSE00003713837	37982364	37982484
ENSE00003721686	37983028	37983076
ENSE00003722018	37980543	37980642
ENSE00003723948	37985878	37985917
ENSE00003731646	37980020	37980172
ENSE00003734891	37987201	37987286
ENSE00003735741	37984325	37984434
ENSE00003742820	37985315	37985395
ENSE00003743047	37978155	37979038
ENSE00003746419	37984764	37984871
ENSE00003751397	37981106	37981171
ENSE00003751567	37981556	37981650
ENSE00003919637	37987449	37989060

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.63.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.63	gold quality
right uterine tube	UBERON:0001302	94.42	gold quality
mucosa of transverse colon	UBERON:0004991	90.11	gold quality
metanephros cortex	UBERON:0010533	90.10	gold quality
cerebellar hemisphere	UBERON:0002245	88.99	gold quality
cerebellar cortex	UBERON:0002129	88.87	gold quality
cerebellum	UBERON:0002037	88.79	gold quality
primary visual cortex	UBERON:0002436	88.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.67	gold quality
right lung	UBERON:0002167	87.22	gold quality
pituitary gland	UBERON:0000007	86.99	gold quality
granulocyte	CL:0000094	86.89	gold quality
right testis	UBERON:0004534	86.48	gold quality
left adrenal gland cortex	UBERON:0035825	86.03	gold quality
endocervix	UBERON:0000458	85.97	gold quality
blood	UBERON:0000178	85.40	gold quality
esophagus mucosa	UBERON:0002469	85.40	gold quality
ectocervix	UBERON:0012249	85.33	gold quality
right lobe of liver	UBERON:0001114	85.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.09	gold quality
anterior cingulate cortex	UBERON:0009835	84.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.71	gold quality
vagina	UBERON:0000996	84.69	gold quality
skin of leg	UBERON:0001511	84.55	gold quality
zone of skin	UBERON:0000014	84.04	gold quality
left adrenal gland	UBERON:0001234	83.71	gold quality
skin of abdomen	UBERON:0001416	83.61	gold quality
right frontal lobe	UBERON:0002810	83.61	gold quality
spleen	UBERON:0002106	83.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TBC1D3L, 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), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 3L — B9A6J9 (reviewed: B9A6J9)

All UniProt accessions (2): B9A6J9, B3KTC5

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 (4): NP_001278388, NP_001356428, NP_001356429, NP_001356430 (=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-B9A6J9-F1	60.31	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: 12 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR335_3P, MIR5585_5P, chr17q12, MANNE_COVID19_NONICU_VS_HEALTHY_DONOR_PLATELETS_UP, MANNE_COVID19_COMBINED_COHORT_VS_HEALTHY_DONOR_PLATELETS_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

6 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3L	GPR32	O75388	0
TBC1D3L	ERVFRD-1	P60508	0
TBC1D3L	CCDC7	Q96M83	0

IntAct

0 interactions, top by confidence:

BioGRID (1): TBC1D3L (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

0 predictions. Top by Δscore:

AlphaMissense

3577 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:37982410:G:C	F207L	0.974
17:37982410:G:T	F207L	0.974
17:37982412:A:G	F207L	0.974
17:37980615:A:G	W286R	0.917
17:37980615:A:T	W286R	0.917
17:37984820:A:G	W111R	0.899
17:37984820:A:T	W111R	0.899
17:37984345:G:C	F159L	0.895
17:37984345:G:T	F159L	0.895
17:37984347:A:G	F159L	0.895
17:37985362:A:G	W78R	0.886
17:37985362:A:T	W78R	0.886
17:37984818:C:A	W111C	0.862
17:37984818:C:G	W111C	0.862
17:37985360:C:A	W78C	0.859
17:37985360:C:G	W78C	0.859
17:37982411:A:G	F207S	0.858
17:37984426:C:A	K132N	0.841
17:37984426:C:G	K132N	0.841
17:37982407:C:A	W208C	0.838
17:37982407:C:G	W208C	0.838
17:37982409:A:G	W208R	0.836
17:37982409:A:T	W208R	0.836
17:37980613:C:A	W286C	0.824
17:37980613:C:G	W286C	0.824
17:37981646:A:C	F224L	0.823
17:37981646:A:T	F224L	0.823
17:37981648:A:G	F224L	0.823
17:37983073:C:A	Q167H	0.822
17:37983073:C:G	Q167H	0.822

dbSNP variants (sampled 300 via entrez): RS1156546577 (17:37978639 T>C), RS1158490393 (17:37982096 A>G), RS1160230203 (17:37980165 GA>G), RS1160236788 (17:37978557 A>G), RS1162108701 (17:37980387 G>A), RS1164507860 (17:37980211 G>T), RS1165589690 (17:37978651 G>A,T), RS1166725670 (17:37979917 T>G), RS1169708392 (17:37981910 C>T), RS1172051406 (17:37982007 C>A,G,T), RS1172843043 (17:37978999 G>A), RS1173425303 (17:37980038 C>T), RS1176648629 (17:37982008 G>A), RS1176787405 (17:37978433 G>A), RS1177467289 (17:37980052 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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
abrine	increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Smoke	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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