TBC1D9B

Summary

TBC1D9B (TBC1 domain family member 9B, HGNC:29097) is a protein-coding gene on chromosome 5q35.3, encoding TBC1 domain family member 9B (Q66K14). May act as a GTPase-activating protein for Rab family protein(s).

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

Source: NCBI Gene 23061 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_015043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29097
Approved symbol	TBC1D9B
Name	TBC1 domain family member 9B
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0676, GRAMD9B
Ensembl gene	ENSG00000197226
Ensembl biotype	protein_coding
OMIM	618039
Entrez	23061

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 13 protein_coding, 8 retained_intron, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355235, ENST00000356834, ENST00000517782, ENST00000518085, ENST00000518115, ENST00000518120, ENST00000518459, ENST00000519746, ENST00000519757, ENST00000520794, ENST00000520912, ENST00000521469, ENST00000521669, ENST00000522029, ENST00000522180, ENST00000522224, ENST00000522472, ENST00000522921, ENST00000524222, ENST00000630103, ENST00000897025, ENST00000897026, ENST00000897027, ENST00000897028, ENST00000897029, ENST00000918454, ENST00000918455

RefSeq mRNA: 2 — MANE Select: NM_015043 NM_015043, NM_198868

CCDS: CCDS43408, CCDS4450

Canonical transcript exons

ENST00000355235 — 21 exons

Exon	Start	End
ENSE00001945720	179907704	179907897
ENSE00002254409	179893209	179893467
ENSE00002263331	179872892	179872990
ENSE00002265379	179899189	179899307
ENSE00002304829	179879628	179879789
ENSE00002310525	179874902	179875187
ENSE00002315304	179879047	179879197
ENSE00002315778	179873119	179873248
ENSE00002454896	179904702	179904812
ENSE00003458385	179894386	179894614
ENSE00003460894	179867778	179867849
ENSE00003478150	179875920	179876037
ENSE00003508076	179891379	179891586
ENSE00003527302	179869769	179869834
ENSE00003538412	179865838	179865888
ENSE00003553325	179878309	179878523
ENSE00003619982	179871462	179871530
ENSE00003638709	179888103	179888312
ENSE00003652380	179870255	179870495
ENSE00003689515	179865254	179865360
ENSE00003907510	179862071	179864128

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7853 / max 254.5026, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65266	29.7853	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.08	gold quality
cerebellar hemisphere	UBERON:0002245	97.76	gold quality
cerebellar cortex	UBERON:0002129	97.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.36	gold quality
right adrenal gland cortex	UBERON:0035827	97.15	gold quality
tibial nerve	UBERON:0001323	97.14	gold quality
right frontal lobe	UBERON:0002810	97.12	gold quality
right adrenal gland	UBERON:0001233	97.10	gold quality
sural nerve	UBERON:0015488	97.03	gold quality
left adrenal gland cortex	UBERON:0035825	96.88	gold quality
stromal cell of endometrium	CL:0002255	96.83	gold quality
left adrenal gland	UBERON:0001234	96.76	gold quality
body of uterus	UBERON:0009853	96.66	gold quality
right ovary	UBERON:0002118	96.61	gold quality
lower esophagus mucosa	UBERON:0035834	96.60	gold quality
skin of leg	UBERON:0001511	96.58	gold quality
skin of abdomen	UBERON:0001416	96.53	gold quality
endocervix	UBERON:0000458	96.51	gold quality
right uterine tube	UBERON:0001302	96.50	gold quality
metanephros cortex	UBERON:0010533	96.50	gold quality
right lobe of thyroid gland	UBERON:0001119	96.43	gold quality
ectocervix	UBERON:0012249	96.35	gold quality
anterior cingulate cortex	UBERON:0009835	96.23	gold quality
left ovary	UBERON:0002119	96.10	gold quality
mucosa of stomach	UBERON:0001199	96.06	gold quality
left uterine tube	UBERON:0001303	96.03	gold quality
minor salivary gland	UBERON:0001830	96.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.00	gold quality
body of pancreas	UBERON:0001150	95.98	gold quality
granulocyte	CL:0000094	95.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting TBC1D9B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119

Literature-anchored findings (GeneRIF, showing 1)

• Study found that TBC1D9B, a GTPase activating protein for RAB11A, interacted with LC3B. TBC1D9B could also interact with other mammalian ATG8 homologues and revealed that TBC1D9B can positively regulate autophagic flux, possibly through its GTPase activity to inactivate RAB11A, facilitating the proper destination of the autophagosomes to the degradation. (PMID:30202024)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d9b	ENSDARG00000043627
mus_musculus	Tbc1d9b	ENSMUSG00000036644
rattus_norvegicus	Tbc1d9b	ENSRNOG00000003050

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), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 9B — Q66K14 (reviewed: Q66K14)

All UniProt accessions (6): A1L3A9, E5RIN2, Q66K14, G3V133, H0YB08, H0YB58

UniProt curated annotations — full annotation on UniProt →

Function. May act as a GTPase-activating protein for Rab family protein(s).

Subcellular location. Membrane.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q66K14-1	1	yes
Q66K14-2	2

RefSeq proteins (2): NP_055858, NP_942568 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR004182	GRAM	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR036014	TCB1D9/TCB1D9B_PH-GRAM1	Domain
IPR036017	TCB1D9/TCB1D9B_PH-GRAM2	Domain

Pfam: PF00566, PF02893

UniProt features (27 total): modified residue 6, domain 4, sequence variant 4, region of interest 4, compositionally biased region 2, site 2, sequence conflict 2, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q66K14-F1	75.41	0.41

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): 555 (arginine finger); 594 (glutamine finger)

Post-translational modifications (6): 397, 411, 432, 435, 463, 1241

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CAGGTCC_MIR492, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CHANDRAN_METASTASIS_DN, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ASSEMBLY, GOBP_REGULATION_OF_ORGANELLE_ASSEMBLY, TGCCTTA_MIR124A, PARENT_MTOR_SIGNALING_UP, LIU_SOX4_TARGETS_DN

GO Biological Process (1): system process (GO:0003008)

GO Molecular Function (3): GTPase activator activity (GO:0005096), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
metal ion binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D9B	RAB11A	P24410	660
TBC1D9B	TBC1D20	Q96BZ9	594
TBC1D9B	TBC1D5	Q92609	543
TBC1D9B	TBC1D21	Q8IYX1	519
TBC1D9B	TBC1D15	Q8TC07	517
TBC1D9B	TBC1D25	Q3MII6	508
TBC1D9B	TBC1D22B	Q9NU19	502
TBC1D9B	SUSD1	Q6UWL2	460
TBC1D9B	TBC1D22A	Q8WUA7	457
TBC1D9B	TBC1D13	Q9NVG8	453
TBC1D9B	TBC1D19	Q8N5T2	447
TBC1D9B	RNF130	Q86XS8	440
TBC1D9B	ATP6V1G2	O95670	439
TBC1D9B	AATK	Q6ZMQ8	432
TBC1D9B	CDC16	Q13042	432

IntAct

87 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TBC1D9	ABHD16A	psi-mi:“MI:0914”(association)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
MYO1D	UBB	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TBC1D9B	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.370
TBC1D9B	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
Batf3	SF3B2	psi-mi:“MI:0914”(association)	0.350
TBC1D9B	CLK2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ATXN1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
TBC1D9B	Smyd1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): TBC1D9B (Two-hybrid), L3MBTL2 (Two-hybrid), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Co-fractionation), CLK2 (Affinity Capture-MS), SEC62 (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS), TBC1D9B (Affinity Capture-MS)

ESM2 similar proteins: A0A0B7P9G0, A0A0R4IMY7, A0JPA0, D3ZAA9, O35454, P0C1Q3, P0C588, P16067, P20594, P32232, P33402, P35525, P46197, P47823, P51432, P51788, Q01970, Q13144, Q14168, Q1LWG4, Q32PX9, Q3TWN3, Q3USB7, Q3V384, Q4U2V3, Q502J0, Q5EBA1, Q5U2P1, Q62688, Q66K14, Q69ZF7, Q6P4Q7, Q7L5N7, Q80YD1, Q8BYI6, Q8CIR4, Q8IYB8, Q8K394, Q8WV93, Q91WT9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

8133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:179893450:A:G	W199R	1.000
5:179893450:A:T	W199R	1.000
5:179894446:C:G	G173R	1.000
5:179899268:A:G	L90P	1.000
5:179904746:A:G	L62P	1.000
5:179904752:C:G	R60P	1.000
5:179907779:A:G	W15R	1.000
5:179907779:A:T	W15R	1.000
5:179907818:A:G	W2R	1.000
5:179907818:A:T	W2R	1.000
5:179876029:G:C	N597K	0.999
5:179876029:G:T	N597K	0.999
5:179878424:T:A	D556V	0.999
5:179878424:T:G	D556A	0.999
5:179878427:C:G	R555P	0.999
5:179879062:A:G	W518R	0.999
5:179879062:A:T	W518R	0.999
5:179879170:A:G	W482R	0.999
5:179879170:A:T	W482R	0.999
5:179894411:G:C	F184L	0.999
5:179894411:G:T	F184L	0.999
5:179894413:A:G	F184L	0.999
5:179894418:A:G	L182P	0.999
5:179894433:A:G	L177P	0.999
5:179894437:A:C	Y176D	0.999
5:179894445:C:T	G173D	0.999
5:179894454:G:T	P170H	0.999
5:179894474:G:C	S163R	0.999
5:179894474:G:T	S163R	0.999
5:179894476:T:G	S163R	0.999

dbSNP variants (sampled 300 via entrez): RS1000046447 (5:179867662 G>A,T), RS1000091683 (5:179867940 T>C), RS1000278172 (5:179874722 C>G), RS1000309278 (5:179874433 G>A), RS1000313955 (5:179862309 G>C), RS1000338094 (5:179884361 C>G,T), RS1000440728 (5:179878854 C>T), RS1000478604 (5:179879916 G>A), RS1000540150 (5:179881281 C>T), RS1000638971 (5:179887250 C>A), RS1000667613 (5:179909263 G>C), RS1000668341 (5:179887011 G>A,C), RS1000775790 (5:179877589 G>C), RS1000912069 (5:179865077 G>A,T), RS1000965160 (5:179901958 C>T)

Disease associations

OMIM: gene MIM:618039 | 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
GCST90011899_165	Aspartate aminotransferase levels	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	2
Acrolein	increases abundance, affects cotreatment, increases oxidation	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
tetrabromobisphenol A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
cupric oxide	decreases expression	1
deguelin	decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	decreases expression, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	increases expression	1
Caffeine	increases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Potassium Dichromate	increases expression	1

Clinical trials (associated diseases)

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