TBC1D12

Summary

TBC1D12 (TBC1 domain family member 12, HGNC:29082) is a protein-coding gene on chromosome 10q23.33, encoding TBC1 domain family member 12 (O60347). RAB11A-binding protein that plays a role in neurite outgrowth.

Predicted to enable GTPase activator activity. Predicted to be involved in regulation of autophagosome assembly. Predicted to be located in endosome. Predicted to be active in autophagosome and recycling endosome.

Source: NCBI Gene 23232 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_015188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29082
Approved symbol	TBC1D12
Name	TBC1 domain family member 12
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0608
Ensembl gene	ENSG00000108239
Ensembl biotype	protein_coding
OMIM	620003
Entrez	23232

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000225235, ENST00000457045, ENST00000485048, ENST00000904398, ENST00000904399, ENST00000904400, ENST00000904401, ENST00000904402, ENST00000904403, ENST00000971287, ENST00000971288, ENST00000971289

RefSeq mRNA: 1 — MANE Select: NM_015188 NM_015188

CCDS: CCDS41553

Canonical transcript exons

ENST00000225235 — 13 exons

Exon	Start	End
ENSE00000715888	94441896	94442019
ENSE00000810844	94493365	94493447
ENSE00000810845	94497055	94497172
ENSE00000810846	94500221	94500327
ENSE00000810847	94507267	94507347
ENSE00000810850	94521955	94522083
ENSE00000810851	94522344	94522453
ENSE00000933023	94474668	94474783
ENSE00001021609	94402541	94403584
ENSE00001162241	94533028	94536332
ENSE00001272582	94510091	94510179
ENSE00003550909	94531202	94531460
ENSE00003598898	94511583	94511654

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5766 / max 162.8225, expressed in 1596 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106318	1.7939	857
106317	1.6512	933
106316	1.5441	916
106319	0.5874	292

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	95.12	gold quality
spinal cord	UBERON:0002240	94.22	gold quality
corpus callosum	UBERON:0002336	92.75	gold quality
inferior olivary complex	UBERON:0002127	91.24	gold quality
inferior vagus X ganglion	UBERON:0005363	90.46	gold quality
medial globus pallidus	UBERON:0002477	88.41	gold quality
subthalamic nucleus	UBERON:0001906	88.12	gold quality
substantia nigra	UBERON:0002038	88.04	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	87.76	gold quality
midbrain	UBERON:0001891	87.33	gold quality
tibia	UBERON:0000979	87.31	gold quality
globus pallidus	UBERON:0001875	87.27	gold quality
medulla oblongata	UBERON:0001896	86.28	gold quality
jejunal mucosa	UBERON:0000399	85.06	gold quality
mucosa of transverse colon	UBERON:0004991	84.97	gold quality
calcaneal tendon	UBERON:0003701	84.62	gold quality
Ammon’s horn	UBERON:0001954	84.24	gold quality
cortical plate	UBERON:0005343	83.88	gold quality
visceral pleura	UBERON:0002401	83.42	gold quality
pons	UBERON:0000988	83.06	gold quality
parietal pleura	UBERON:0002400	83.05	gold quality
pleura	UBERON:0000977	82.89	gold quality
hypothalamus	UBERON:0001898	82.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.87	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.49	gold quality
superior vestibular nucleus	UBERON:0007227	82.34	gold quality
putamen	UBERON:0001874	82.26	gold quality
primary visual cortex	UBERON:0002436	81.80	gold quality
ventricular zone	UBERON:0003053	81.80	gold quality
amygdala	UBERON:0001876	81.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting TBC1D12, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
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-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d12b	ENSDARG00000073771
danio_rerio		ENSDARG00000112088
mus_musculus	Tbc1d12	ENSMUSG00000048720
rattus_norvegicus	Tbc1d12	ENSRNOG00000036598

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), 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), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 12 — O60347 (reviewed: O60347)

All UniProt accessions (1): O60347

UniProt curated annotations — full annotation on UniProt →

Function. RAB11A-binding protein that plays a role in neurite outgrowth.

Subunit / interactions. Interacts with RAB11A; this interaction recruits TBC1D12 to RAB11A-positive recycling endosomes.

Subcellular location. Endosome.

RefSeq proteins (1): NP_056003* (*=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 (18 total): modified residue 5, compositionally biased region 5, sequence conflict 3, region of interest 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60347-F1	64.59	0.39

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 (5): 1, 284, 315, 747, 748

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): GOBP_VACUOLE_ORGANIZATION, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MACROAUTOPHAGY, MORF_ZNF10, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_ORGANELLE_ASSEMBLY, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CUI_TCF21_TARGETS_2_DN, GOBP_REGULATION_OF_ORGANELLE_ASSEMBLY

GO Biological Process (2): vesicle-mediated transport (GO:0016192), regulation of autophagosome assembly (GO:2000785)

GO Molecular Function (2): GTPase activator activity (GO:0005096), enzyme binding (GO:0019899)

GO Cellular Component (5): autophagosome (GO:0005776), recycling endosome (GO:0055037), endosome (GO:0005768), vacuole (GO:0005773), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
transport	1
cellular process	1
autophagosome assembly	1
regulation of vacuole organization	1
regulation of organelle assembly	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein binding	1
vacuole	1
endosome	1
endomembrane system	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D12	PLEKHS1	Q5SXH7	671
TBC1D12	LEPROTL1	O95214	615
TBC1D12	WDR74	Q6RFH5	584
TBC1D12	TBC1D19	Q8N5T2	546
TBC1D12	TBC1D21	Q8IYX1	526
TBC1D12	SGSM2	O43147	519
TBC1D12	CCDC107	Q8WV48	513
TBC1D12	TBC1D23	Q9NUY8	509
TBC1D12	TBC1D13	Q9NVG8	458
TBC1D12	PLCE1	Q9P212	453
TBC1D12	C3orf70	A6NLC5	447
TBC1D12	MB21D2	Q8IYB1	444
TBC1D12	TBC1D7	Q9P0N9	441
TBC1D12	FBXO8	Q9NRD0	418
TBC1D12	CCDC158	Q5M9N0	416

IntAct

3 interactions, top by confidence:

A	B	Type	Score
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): TBC1D12 (Affinity Capture-MS), TBC1D12 (Synthetic Lethality), TBC1D12 (Proximity Label-MS), TBC1D12 (Affinity Capture-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Affinity Capture-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS), TBC1D12 (Proximity Label-MS)

ESM2 similar proteins: A1A5B6, A6H7I8, A7E300, B9VTT2, F1LXF1, M0R7T9, O08873, O14795, O60347, O60447, P0C6S7, P11274, P22681, P22682, P49797, Q0IHY4, Q0VGY8, Q14432, Q3MII6, Q4KUS2, Q5CD77, Q62769, Q69ZT9, Q6A039, Q6F6B3, Q6P9S0, Q6PAJ1, Q6PCS4, Q6ZM89, Q765P7, Q80U28, Q80YA9, Q8BIZ1, Q8CGA2, Q8K214, Q8R1S4, Q8WXG6, Q8WXI2, Q923Q2, Q92625

Diamond homologs: A6H7I8, M0R7T9, O60347, O96904, Q0IHY4, Q10496, Q5CD77, Q6A039, Q86UD7, Q8CGA2, Q96CN4, Q9P2M4, A2AWA9, Q5RAN1, Q755I4, Q9Y3P9, Q9Y7J5, Q5R372, Q5RCW6, A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A3KGB4, A6H6A9, A6NDS4, A6NER0, A6QP29, B9A6J9, D2H0G5, H2KZZ6, O60343, O95759, O97790, P0C7X1, P35125, P53258, P58802, Q0IIM8, Q28CB1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2876 predictions. Top by Δscore:

Variant	Effect	Δscore
10:94429374:GCC:G	donor_gain	1.0000
10:94441891:TTCA:T	acceptor_loss	1.0000
10:94441892:TCAG:T	acceptor_loss	1.0000
10:94441893:CA:C	acceptor_loss	1.0000
10:94441894:A:AG	acceptor_gain	1.0000
10:94441894:AG:A	acceptor_loss	1.0000
10:94441895:G:GT	acceptor_gain	1.0000
10:94441895:GA:G	acceptor_gain	1.0000
10:94441895:GAA:G	acceptor_gain	1.0000
10:94441895:GAAA:G	acceptor_gain	1.0000
10:94441895:GAAAC:G	acceptor_gain	1.0000
10:94442015:AGCAG:A	donor_gain	1.0000
10:94442016:GCAGG:G	donor_gain	1.0000
10:94442017:CAGG:C	donor_loss	1.0000
10:94442018:AGG:A	donor_loss	1.0000
10:94442020:G:GA	donor_loss	1.0000
10:94442020:G:GG	donor_gain	1.0000
10:94442021:T:A	donor_loss	1.0000
10:94443326:A:G	acceptor_gain	1.0000
10:94444438:T:TA	acceptor_gain	1.0000
10:94474664:CTAG:C	acceptor_loss	1.0000
10:94474666:A:AC	acceptor_loss	1.0000
10:94474667:G:GC	acceptor_loss	1.0000
10:94474779:CCATC:C	donor_gain	1.0000
10:94474780:CATC:C	donor_gain	1.0000
10:94474781:ATC:A	donor_gain	1.0000
10:94474782:TC:T	donor_gain	1.0000
10:94474782:TCGTA:T	donor_loss	1.0000
10:94474784:G:GG	donor_gain	1.0000
10:94474785:TA:T	donor_loss	1.0000

AlphaMissense

5057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:94474765:T:C	I398T	1.000
10:94497138:T:A	W460R	1.000
10:94497138:T:C	W460R	1.000
10:94500249:T:A	W481R	1.000
10:94500249:T:C	W481R	1.000
10:94500258:G:A	G484R	1.000
10:94500258:G:C	G484R	1.000
10:94500259:G:A	G484E	1.000
10:94500274:T:A	V489D	1.000
10:94500276:C:A	R490S	1.000
10:94500277:G:C	R490P	1.000
10:94500286:T:A	V493D	1.000
10:94500288:T:A	W494R	1.000
10:94500288:T:C	W494R	1.000
10:94500289:G:C	W494S	1.000
10:94500290:G:C	W494C	1.000
10:94500290:G:T	W494C	1.000
10:94500313:T:C	L502P	1.000
10:94507270:T:C	L508P	1.000
10:94510130:T:A	I547N	1.000
10:94510138:G:C	D550H	1.000
10:94510138:G:T	D550Y	1.000
10:94510139:A:C	D550A	1.000
10:94510139:A:G	D550G	1.000
10:94510139:A:T	D550V	1.000
10:94510140:C:A	D550E	1.000
10:94510140:C:G	D550E	1.000
10:94510142:T:A	I551K	1.000
10:94510148:G:C	R553P	1.000
10:94510151:C:A	T554K	1.000

dbSNP variants (sampled 300 via entrez): RS1000013155 (10:94529459 A>C), RS1000023686 (10:94469196 A>G), RS1000036331 (10:94514906 T>C), RS1000044128 (10:94426734 A>G), RS1000045445 (10:94440487 T>C), RS1000076260 (10:94486674 T>C,G), RS1000149877 (10:94401638 C>G), RS1000154262 (10:94445110 C>T), RS1000155208 (10:94498751 C>A), RS1000165897 (10:94536128 G>A,T), RS1000173999 (10:94407399 C>A), RS1000174860 (10:94410751 G>C), RS1000184841 (10:94444752 G>A,T), RS1000220420 (10:94402745 C>T), RS1000230853 (10:94445234 C>G)

Disease associations

OMIM: gene MIM:620003 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004621_16	Red cell distribution width	2.000000e-13
GCST006206_3	Thiopurine-induced alopecia in inflammatory bowel disease	1.000000e-06
GCST006804_54	Red cell distribution width	6.000000e-13
GCST007684_2	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	5.000000e-14
GCST009174_2	Response to (pegylated) interferon in chronic hepatitis B	1.000000e-06
GCST010397_80	Gut microbiota (bacterial taxa, rank normal transformation method)	7.000000e-06
GCST90002396_490	Mean reticulocyte volume	1.000000e-33
GCST90002398_181	Neutrophil count	3.000000e-18
GCST90002403_223	Red blood cell count	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0007859	response to interferon
EFO:0007874	gut microbiome measurement
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Folic Acid	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Melphalan	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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