TBC1D26

Summary

TBC1D26 (TBC1 domain family member 26, HGNC:28745) is a protein-coding gene on chromosome 17p12, encoding TBC1 domain family member 26 (Q86UD7). May act as a GTPase-activating protein for Rab family protein(s).

Predicted to enable GTPase activator activity.

Source: NCBI Gene 353149 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total — 1 pathogenic
• MANE Select transcript: NM_001388465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28745
Approved symbol	TBC1D26
Name	TBC1 domain family member 26
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	MGC51025
Ensembl gene	ENSG00000214946
Ensembl biotype	protein_coding
Entrez	353149

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000437605, ENST00000464963, ENST00000469477, ENST00000491819, ENST00000578506, ENST00000579428, ENST00000580596, ENST00000580970, ENST00000582140, ENST00000582534, ENST00000583620, ENST00000584301

RefSeq mRNA: 2 — MANE Select: NM_001388465 NM_001388465, NM_178571

CCDS: CCDS42265, CCDS92260

Canonical transcript exons

ENST00000437605 — 15 exons

Exon	Start	End
ENSE00001668197	15732283	15732384
ENSE00002818621	15744243	15744782
ENSE00003478308	15735348	15735423
ENSE00003645880	15734930	15735070
ENSE00003802175	15738280	15738387
ENSE00003802746	15738721	15738830
ENSE00003803919	15735597	15735679
ENSE00003807163	15740100	15740148
ENSE00003809379	15737997	15738077
ENSE00003810038	15737484	15737523
ENSE00003923451	15741942	15742036
ENSE00003925305	15742414	15742479
ENSE00003929125	15743367	15743516
ENSE00003932626	15741122	15741221
ENSE00003934722	15742909	15743008

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 87.21.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	87.21	gold quality
left testis	UBERON:0004533	86.55	gold quality
testis	UBERON:0000473	85.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.48	gold quality
nucleus accumbens	UBERON:0001882	75.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.38	silver quality
putamen	UBERON:0001874	73.91	gold quality
caudate nucleus	UBERON:0001873	72.26	gold quality
Ammon’s horn	UBERON:0001954	69.16	gold quality
right frontal lobe	UBERON:0002810	67.30	gold quality
superior frontal gyrus	UBERON:0002661	67.20	gold quality
temporal lobe	UBERON:0001871	65.27	gold quality
amygdala	UBERON:0001876	65.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.91	gold quality
anterior cingulate cortex	UBERON:0009835	63.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	63.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.95	gold quality
primary visual cortex	UBERON:0002436	62.82	gold quality
cerebral cortex	UBERON:0000956	62.50	gold quality
mucosa of stomach	UBERON:0001199	61.32	gold quality
brain	UBERON:0000955	61.06	gold quality
right uterine tube	UBERON:0001302	60.20	gold quality
cortical plate	UBERON:0005343	59.73	gold quality
frontal cortex	UBERON:0001870	59.29	gold quality
spleen	UBERON:0002106	59.24	gold quality
ventricular zone	UBERON:0003053	57.49	gold quality
granulocyte	CL:0000094	55.24	gold quality
body of uterus	UBERON:0009853	54.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	54.84	gold quality
lower esophagus mucosa	UBERON:0035834	54.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting TBC1D26, 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-5193	100.00	67.26	1744
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888

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), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 26 — Q86UD7 (reviewed: Q86UD7)

All UniProt accessions (6): A0A8J8ZQP4, Q86UD7, J3QLL4, J3QQK9, J3QR66, J3QRI5

UniProt curated annotations — full annotation on UniProt →

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q86UD7-1	1	yes
Q86UD7-2	2
Q86UD7-3	3

RefSeq proteins (2): NP_001375394, NP_848666 (=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 (9 total): splice variant 4, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UD7-F1	76.42	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): chr17p12, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR205_5P, MIR3124_3P, MIR202_5P, MIR3194_5P, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, ZNF320_TARGET_GENES, GOMF_GTPASE_ACTIVATOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (0):

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 interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D26	CDRT15L2	A8MXV6	582
TBC1D26	OR2T29	Q8NH02	480
TBC1D26	SLC35G3	Q8N808	479
TBC1D26	CCDC144A	A2RUR9	479
TBC1D26	SLC35G6	P0C7Q6	479
TBC1D26	SPDYE4	A6NLX3	472
TBC1D26	OR3A2	P47893	472
TBC1D26	CHCT1	Q86WR6	447
TBC1D26	LRRC3C	A6NJW4	433
TBC1D26	POTEC	B2RU33	432
TBC1D26	FBXW10B	O95170	432
TBC1D26	TMEM95	Q3KNT9	420
TBC1D26	TBC1D22B	Q9NU19	418
TBC1D26	MFSD6L	Q8IWD5	414
TBC1D26	TBC1D19	Q8N5T2	411

IntAct

0 interactions, top by confidence:

BioGRID (12): TBC1D26 (Reconstituted Complex), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid), TBC1D26 (Two-hybrid)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A0JN92, A4D126, A6NDS4, A6NER0, A7VL23, B9A6J9, C3VPR6, D4A693, E0CYC6, E0CYR6, P0C7X1, P0C7X4, P85118, Q01534, Q3UX83, Q4AC99, Q4KM84, Q52LC2, Q5NCI0, Q5RFJ8, Q61085, Q63764, Q6DHY5, Q6IPX1, Q6PRD1, Q7Z443, Q86UD7, Q8BVM4, Q8C262, Q8CHQ9, Q8IWD5, Q8IZP1, Q8N8A8, Q8R3N2, Q8TCY9, Q96A70

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703602	Single allele	Pathogenic

SpliceAI

2540 predictions. Top by Δscore:

Variant	Effect	Δscore
17:15737482:A:AG	acceptor_gain	1.0000
17:15737483:G:GG	acceptor_gain	1.0000
17:15738826:GTCAA:G	donor_gain	1.0000
17:15738827:TC:T	donor_gain	1.0000
17:15738831:G:GG	donor_gain	1.0000
17:15743006:GGA:G	donor_gain	1.0000
17:15743007:GAG:G	donor_gain	1.0000
17:15743009:G:GG	donor_gain	1.0000
17:15735410:C:CG	donor_gain	0.9900
17:15735414:G:GG	donor_gain	0.9900
17:15735680:G:GG	donor_gain	0.9900
17:15737481:CAGTG:C	acceptor_gain	0.9900
17:15737482:AGTGA:A	acceptor_gain	0.9900
17:15737483:GT:G	acceptor_gain	0.9900
17:15737483:GTGA:G	acceptor_gain	0.9900
17:15737483:GTGAG:G	acceptor_gain	0.9900
17:15738279:GCT:G	acceptor_gain	0.9900
17:15738715:CTACA:C	acceptor_loss	0.9900
17:15738718:CAGG:C	acceptor_loss	0.9900
17:15738720:G:A	acceptor_loss	0.9900
17:15738827:TCAAG:T	donor_loss	0.9900
17:15738829:AAG:A	donor_loss	0.9900
17:15738830:AG:A	donor_loss	0.9900
17:15738831:G:GC	donor_loss	0.9900
17:15738832:TAAG:T	donor_loss	0.9900
17:15740145:CCCT:C	donor_gain	0.9900
17:15740149:G:GG	donor_gain	0.9900
17:15743004:CAGGA:C	donor_gain	0.9900
17:15743005:AGGA:A	donor_gain	0.9900
17:15743006:GGAG:G	donor_gain	0.9900

AlphaMissense

3191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:15741194:T:C	F207L	0.933
17:15741196:C:A	F207L	0.933
17:15741196:C:G	F207L	0.933
17:15738808:T:C	F159L	0.930
17:15738810:C:A	F159L	0.930
17:15738810:C:G	F159L	0.930
17:15738820:T:C	F163L	0.885
17:15738822:C:A	F163L	0.885
17:15738822:C:G	F163L	0.885
17:15738729:G:C	K132N	0.823
17:15738729:G:T	K132N	0.823
17:15738030:T:A	W78R	0.811
17:15738030:T:C	W78R	0.811
17:15738363:G:C	K121N	0.776
17:15738363:G:T	K121N	0.776
17:15738032:G:C	W78C	0.774
17:15738032:G:T	W78C	0.774
17:15738726:G:A	M131I	0.739
17:15738726:G:C	M131I	0.739
17:15738726:G:T	M131I	0.739
17:15740111:T:C	L170S	0.731
17:15741199:G:C	W208C	0.713
17:15741199:G:T	W208C	0.713
17:15738331:T:A	W111R	0.707
17:15738331:T:C	W111R	0.707
17:15740103:G:C	Q167H	0.707
17:15740103:G:T	Q167H	0.707
17:15741197:T:A	W208R	0.706
17:15741197:T:C	W208R	0.706
17:15738809:T:C	F159S	0.683

dbSNP variants (sampled 300 via entrez): RS1000015741 (17:15734789 A>G), RS1000067971 (17:15735035 C>G), RS1000084231 (17:15741731 G>T), RS1001190518 (17:15734587 G>A,T), RS1002136316 (17:15730480 C>T), RS1003591080 (17:15740279 G>C,T), RS1003642150 (17:15733362 G>A), RS1003937732 (17:15733537 G>T), RS1004141325 (17:15732929 G>A), RS1004435635 (17:15733232 G>A,T), RS1004828173 (17:15739531 A>G), RS1004944004 (17:15739066 GAAAA>G,GAA,GAAA,GAAAAA), RS1005136228 (17:15745128 T>C), RS1005431491 (17:15744724 A>G), RS1005494100 (17:15736214 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616652

GenCC curated gene-disease

Mondo (1): PMP22-RAI1 contiguous gene duplication syndrome (MONDO:0014723)

Orphanet (1): PMP22-RAI1 contiguous gene duplication syndrome (Orphanet:477817)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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