TBC1D22B

Summary

TBC1D22B (TBC1 domain family member 22B, HGNC:21602) is a protein-coding gene on chromosome 6p21.2, encoding TBC1 domain family member 22B (Q9NU19). May act as a GTPase-activating protein for Rab family protein(s).

Enables 14-3-3 protein binding activity. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 55633 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_017772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21602
Approved symbol	TBC1D22B
Name	TBC1 domain family member 22B
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20337, dJ744I24.2
Ensembl gene	ENSG00000065491
Ensembl biotype	protein_coding
OMIM	616880
Entrez	55633

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000373491, ENST00000869078, ENST00000869079, ENST00000942344

RefSeq mRNA: 1 — MANE Select: NM_017772 NM_017772

CCDS: CCDS4832

Canonical transcript exons

ENST00000373491 — 13 exons

Exon	Start	End
ENSE00000750052	37284336	37284464
ENSE00000750053	37287007	37287072
ENSE00000750054	37291243	37291357
ENSE00000750072	37316703	37316830
ENSE00000849780	37317111	37317206
ENSE00001171658	37312918	37313024
ENSE00001370113	37282185	37282364
ENSE00001374511	37279304	37279611
ENSE00001381460	37282882	37282952
ENSE00001386702	37269594	37269650
ENSE00001460685	37331044	37332970
ENSE00001460698	37257772	37257973
ENSE00002453110	37313816	37313891

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 87.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5587 / max 217.3009, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67625	19.3300	1811
67626	0.2287	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	87.14	gold quality
esophagus squamous epithelium	UBERON:0006920	85.81	gold quality
secondary oocyte	CL:0000655	85.56	gold quality
oocyte	CL:0000023	85.10	gold quality
islet of Langerhans	UBERON:0000006	83.53	gold quality
gastrocnemius	UBERON:0001388	83.44	gold quality
ventricular zone	UBERON:0003053	83.34	gold quality
skin of abdomen	UBERON:0001416	83.17	gold quality
skin of leg	UBERON:0001511	83.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.96	gold quality
right adrenal gland cortex	UBERON:0035827	82.79	gold quality
esophagus mucosa	UBERON:0002469	82.35	gold quality
left adrenal gland	UBERON:0001234	82.32	gold quality
left adrenal gland cortex	UBERON:0035825	82.19	gold quality
adrenal cortex	UBERON:0001235	82.15	gold quality
right adrenal gland	UBERON:0001233	82.11	gold quality
muscle of leg	UBERON:0001383	81.93	gold quality
tibia	UBERON:0000979	81.19	gold quality
zone of skin	UBERON:0000014	81.17	gold quality
minor salivary gland	UBERON:0001830	81.12	gold quality
adrenal gland	UBERON:0002369	81.10	gold quality
saliva-secreting gland	UBERON:0001044	80.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.77	gold quality
ganglionic eminence	UBERON:0004023	80.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.60	gold quality
tendon of biceps brachii	UBERON:0008188	80.52	silver quality
mucosa of transverse colon	UBERON:0004991	80.35	gold quality
esophagus	UBERON:0001043	80.33	gold quality
mouth mucosa	UBERON:0003729	80.28	gold quality
oral cavity	UBERON:0000167	80.09	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting TBC1D22B, 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-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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 1)

• Using affinity purification-mass spectrometry, we identified the putative Rab33 GTPase-activating proteins TBC1D22A and TBC1D22B as ACBD3-interacting factors. (PMID:23572552)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d22b	ENSDARG00000026988
mus_musculus	Tbc1d22b	ENSMUSG00000042203
rattus_norvegicus	Tbc1d22b	ENSRNOG00000059458

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), 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), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 22B — Q9NU19 (reviewed: Q9NU19)

All UniProt accessions (1): Q9NU19

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Interacts with ACBD3 and ARFGEF1. Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ.

RefSeq proteins (1): NP_060242* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00566

UniProt features (47 total): helix 21, mutagenesis site 12, modified residue 4, strand 2, turn 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6D0S	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NU19-F1	76.87	0.61

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 (4): 2, 58, 116, 154

Mutagenesis-validated functional residues (12):

Position	Phenotype
88–90	no effect on acbd3-binding.
91–92	no effect on acbd3-binding.
94–96	no effect on acbd3-binding.
99	no effect on acbd3-binding.
100–101	almost complete loss of acbd3-binding.
102–104	no effect on acbd3-binding.
114	no effect on acbd3-binding.
116–119	no effect on acbd3-binding.
140–141	no effect on acbd3-binding.
143	no effect on acbd3-binding.
168	no effect on acbd3-binding.
58	no effect on acbd3-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_CILIUM_ASSEMBLY, GCM_NF2, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ASSEMBLY, GOBP_REGULATION_OF_ORGANELLE_ASSEMBLY, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, BENPORATH_OCT4_TARGETS, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_14_3_3_PROTEIN_BINDING, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (3): GTPase activator activity (GO:0005096), 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515)

GO Cellular Component (1): Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1593 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D22B	PROCA1	Q8NCQ7	708
TBC1D22B	PPP2R2D	Q66LE6	651
TBC1D22B	TBC1D21	Q8IYX1	646
TBC1D22B	TBC1D10A	Q9BXI6	624
TBC1D22B	TBC1D10B	Q4KMP7	607
TBC1D22B	TBC1D10C	Q8IV04	593
TBC1D22B	TBC1D19	Q8N5T2	573
TBC1D22B	TBC1D20	Q96BZ9	564
TBC1D22B	TBC1D3B	A6NDS4	530
TBC1D22B	TBC1D8	O95759	516
TBC1D22B	TBC1D30	Q9Y2I9	515
TBC1D22B	GJD4	Q96KN9	512
TBC1D22B	TBC1D9B	Q66K14	502
TBC1D22B	BKGD	Q9H0W9	490
TBC1D22B	SGSM2	O43147	482

IntAct

246 interactions, top by confidence:

A	B	Type	Score
TBC1D22B	TRIM23	psi-mi:“MI:0915”(physical association)	0.830
IKZF3	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.830
TRIM23	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.830
TBC1D22B	IKZF3	psi-mi:“MI:0915”(physical association)	0.830
VPS52	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.780
TBC1D22B	HSD17B14	psi-mi:“MI:0915”(physical association)	0.780
TBC1D22B	TACC3	psi-mi:“MI:0915”(physical association)	0.780
TBC1D22B	VPS52	psi-mi:“MI:0915”(physical association)	0.780
HSD17B14	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.780
TACC3	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.780
FXR2	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.740
TRIM54	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.740
TBC1D22B	FXR2	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (298): TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TBC1D22B (Two-hybrid), TEX11 (Two-hybrid), TRIM54 (Two-hybrid)

ESM2 similar proteins: A1A5K6, A6H8I2, F1M386, F1PBJ0, F1QRX7, F1QWA8, F6UMY3, O02697, O14830, O97790, P26675, P48736, Q08CX5, Q21029, Q29RJ2, Q2KI13, Q3UUG6, Q3UYK3, Q3V3E1, Q5E9C4, Q5R8B7, Q5SVR0, Q5ZJX5, Q66K14, Q6DDI6, Q6DDZ9, Q6DEY8, Q6P6R7, Q6ZT07, Q7T2D0, Q8BGG7, Q8CHG7, Q8R5A6, Q8TC07, Q8TEU7, Q8TF42, Q8VCZ6, Q8WZA2, Q91WS7, Q95LL3

Diamond homologs: O59737, Q08484, Q8R5A6, Q8WUA7, Q95KI1, Q95LL3, Q9NU19, Q54VM3, Q54TA5, Q6FWI1, Q8R3D1, Q9NVG8, Q9URY3, P48365

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2384 predictions. Top by Δscore:

Variant	Effect	Δscore
6:37257947:G:GT	donor_gain	1.0000
6:37257971:G:T	donor_gain	1.0000
6:37257971:GAGGT:G	donor_loss	1.0000
6:37257972:AGG:A	donor_loss	1.0000
6:37257973:GGTG:G	donor_loss	1.0000
6:37257974:G:C	donor_loss	1.0000
6:37257975:T:G	donor_loss	1.0000
6:37269579:T:TA	acceptor_gain	1.0000
6:37269585:T:A	acceptor_gain	1.0000
6:37269591:TA:T	acceptor_loss	1.0000
6:37269592:A:AG	acceptor_gain	1.0000
6:37269593:G:GA	acceptor_gain	1.0000
6:37269593:GC:G	acceptor_gain	1.0000
6:37269593:GCA:G	acceptor_gain	1.0000
6:37269593:GCAT:G	acceptor_gain	1.0000
6:37269593:GCATT:G	acceptor_gain	1.0000
6:37269647:AAAA:A	donor_gain	1.0000
6:37269648:AAA:A	donor_gain	1.0000
6:37269649:AA:A	donor_gain	1.0000
6:37269650:AG:A	donor_loss	1.0000
6:37269651:G:GG	donor_gain	1.0000
6:37279302:A:AG	acceptor_gain	1.0000
6:37279303:G:GG	acceptor_gain	1.0000
6:37279303:GT:G	acceptor_gain	1.0000
6:37279303:GTTTC:G	acceptor_gain	1.0000
6:37279607:CTCTA:C	donor_gain	1.0000
6:37279609:CTAGT:C	donor_loss	1.0000
6:37279610:TA:T	donor_gain	1.0000
6:37279610:TAG:T	donor_loss	1.0000
6:37279612:G:GG	donor_gain	1.0000

AlphaMissense

3344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:37279398:T:A	W70R	1.000
6:37279398:T:C	W70R	1.000
6:37282888:T:C	L203P	1.000
6:37282902:T:A	W208R	1.000
6:37282902:T:C	W208R	1.000
6:37282904:G:C	W208C	1.000
6:37282904:G:T	W208C	1.000
6:37282938:T:A	W220R	1.000
6:37282938:T:C	W220R	1.000
6:37282940:G:C	W220C	1.000
6:37282940:G:T	W220C	1.000
6:37282945:T:C	L222P	1.000
6:37282948:T:C	L223P	1.000
6:37284343:T:C	L227P	1.000
6:37284382:G:C	R240P	1.000
6:37284386:G:C	K241N	1.000
6:37284386:G:T	K241N	1.000
6:37284396:T:C	Y245H	1.000
6:37284396:T:G	Y245D	1.000
6:37284463:A:C	Q267P	1.000
6:37284464:G:C	Q267H	1.000
6:37284464:G:T	Q267H	1.000
6:37287008:T:A	I268N	1.000
6:37287008:T:C	I268T	1.000
6:37287008:T:G	I268S	1.000
6:37287016:G:A	D271N	1.000
6:37287016:G:C	D271H	1.000
6:37287016:G:T	D271Y	1.000
6:37287017:A:C	D271A	1.000
6:37287017:A:G	D271G	1.000

dbSNP variants (sampled 300 via entrez): RS1000035975 (6:37304969 C>G,T), RS1000066826 (6:37270941 G>A), RS1000100958 (6:37303653 T>C), RS1000305965 (6:37298667 T>C), RS1000358432 (6:37284959 T>C), RS1000365455 (6:37326120 G>A), RS1000379688 (6:37289015 A>G), RS1000410923 (6:37288624 C>T), RS1000442748 (6:37331291 C>A,G), RS1000605643 (6:37294343 A>C), RS1000678505 (6:37296048 A>G), RS1000699166 (6:37324879 C>T), RS1000701885 (6:37280882 T>C), RS1000712179 (6:37287532 T>G), RS1000748534 (6:37287216 C>T)

Disease associations

OMIM: gene MIM:616880 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002481_11	Acne (severe)	2.000000e-06
GCST004603_24	Platelet count	5.000000e-12
GCST010660_19	Triglyceride levels	4.000000e-11
GCST010661_6	Blood glucose levels	5.000000e-06
GCST010662_5	Systolic blood pressure	1.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004530	triglyceride measurement
EFO:0004468	glucose measurement
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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