TBC1D3F

Summary

TBC1D3F (TBC1 domain family member 3F, HGNC:18257) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3F (A6NER0). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 84218 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 7 total — 1 likely-pathogenic

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18257
Approved symbol	TBC1D3F
Name	TBC1 domain family member 3F
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000275954
Ensembl biotype	protein_coding
OMIM	610809
Entrez	84218

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding_LoF

ENST00000620210

RefSeq mRNA: 1 — MANE Select: None NM_032258

Canonical transcript exons

ENST00000620210 — 15 exons

Exon	Start	End
ENSE00003717086	36437910	36437982
ENSE00003719361	36434786	36434895
ENSE00003722854	36431564	36431629
ENSE00003723262	36428612	36429092
ENSE00003726618	36433486	36433534
ENSE00003728633	36431001	36431100
ENSE00003733793	36432822	36432942
ENSE00003734621	36430478	36430630
ENSE00003738498	36439411	36439566
ENSE00003743204	36435776	36435856
ENSE00003747436	36435225	36435332
ENSE00003750273	36437662	36437747
ENSE00003750615	36432014	36432108
ENSE00003754120	36436339	36436378
ENSE00004282935	36429094	36429496

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 80.60.

Top tissues by expression

131 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	80.60	silver quality
right testis	UBERON:0004534	68.78	gold quality
testis	UBERON:0000473	63.89	gold quality
left testis	UBERON:0004533	63.78	gold quality
right uterine tube	UBERON:0001302	54.16	gold quality
left uterine tube	UBERON:0001303	43.77	gold quality
bone marrow	UBERON:0002371	43.63	gold quality
granulocyte	CL:0000094	42.35	silver quality
duodenum	UBERON:0002114	40.64	gold quality
lower esophagus mucosa	UBERON:0035834	40.36	silver quality
skeletal muscle tissue	UBERON:0001134	39.76	gold quality
gall bladder	UBERON:0002110	39.15	gold quality
muscle tissue	UBERON:0002385	39.05	gold quality
blood	UBERON:0000178	38.99	gold quality
right coronary artery	UBERON:0001625	38.13	gold quality
smooth muscle tissue	UBERON:0001135	37.87	gold quality
fallopian tube	UBERON:0003889	37.77	gold quality
fundus of stomach	UBERON:0001160	37.50	gold quality
cerebellum	UBERON:0002037	37.38	gold quality
cerebellar hemisphere	UBERON:0002245	37.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cerebellar cortex	UBERON:0002129	37.05	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	36.18	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
mucosa of transverse colon	UBERON:0004991	35.29	gold quality
uterine cervix	UBERON:0000002	34.39	gold quality
muscle of leg	UBERON:0001383	34.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• PRC17 is amplified in 15% of prostate cancers, it is highly overexpressed in approximately one-half of metastatic prostate tumors. (PMID:12359748)
• We describe eight highly related TBC1D3 paralogues located on Chromosome 17q12 that display specific transcription patterns in human tissues, and that pattern is altered in several primary prostate tumors in comparison to healthy prostate tissues. (PMID:16863688)

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), TBC1D3L (ENSG00000274512)

Protein

Protein identifiers

TBC1 domain family member 3F — A6NER0 (reviewed: A6NER0)

All UniProt accessions (2): A6NER0, A0A087WT91

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.

Tissue specificity. Expressed in most tissues including pancreas, thymus and testis.

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_115634 (*=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-A6NER0-F1	60.58	0.24

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: 18 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, JOHNSTONE_PARVB_TARGETS_3_UP, MIR335_3P, MIR5585_5P, chr17q12, NIKOLSKY_BREAST_CANCER_17Q11_Q21_AMPLICON, NAKAYA_B_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_UP, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, GOCC_ENDOSOME, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_UP, GOMF_GTPASE_ACTIVATOR_ACTIVITY, ELVIDGE_HYPOXIA_UP

GO Biological Process (0):

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

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
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TBC1D3F	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
TBC1D3F	CLIC3	psi-mi:“MI:0915”(physical association)	0.560
TBC1D3F	WDR83	psi-mi:“MI:0915”(physical association)	0.400
	TBC1D3F	psi-mi:“MI:0914”(association)	0.350
TBC1D3F	ZRANB1	psi-mi:“MI:0915”(physical association)	0.000
CLIC3	TBC1D3F	psi-mi:“MI:0915”(physical association)	0.000

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	2
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815932	GRCh37/hg19 17q12(chr17:36067413-36410559)x3	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3224 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001261758 (17:36439580 C>A,G,T), RS1010418967 (17:36434799 G>A,T), RS1034056076 (17:36439596 C>T), RS1041575419 (17:36433989 G>A,C), RS112039081 (17:36440467 C>T), RS1156239210 (17:36437980 A>G), RS1156509607 (17:36436471 C>T), RS1156638529 (17:36439772 G>T), RS1156674530 (17:36429282 A>G), RS1156782536 (17:36439038 C>T), RS1156826582 (17:36439854 C>A,T), RS1157071143 (17:36441153 G>A,C), RS1157277335 (17:36430220 G>C), RS1157460318 (17:36439928 A>G), RS1157859650 (17:36433406 A>G)

Disease associations

OMIM: gene MIM:610809 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001941_16	Ovarian cancer	8.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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