TBL1Y

Summary

TBL1Y (transducin beta like 1 Y-linked, HGNC:18502) is a protein-coding gene on chromosome Yp11.2, encoding F-box-like/WD repeat-containing protein TBL1Y (Q9BQ87). F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units.

The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene is highly similar to TBL1X gene in nucleotide sequence and protein sequence, but the TBL1X gene is located on chromosome X and this gene is on chromosome Y. This gene has three alternatively spliced transcript variants encoding the same protein.

Source: NCBI Gene 90665 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_033284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18502
Approved symbol	TBL1Y
Name	transducin beta like 1 Y-linked
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Aliases	TBL1
Ensembl gene	ENSG00000092377
Ensembl biotype	protein_coding
OMIM	400033
Entrez	90665

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000346432, ENST00000355162, ENST00000383032, ENST00000651523

RefSeq mRNA: 3 — MANE Select: NM_033284 NM_033284, NM_134258, NM_134259

CCDS: CCDS14779

Canonical transcript exons

ENST00000383032 — 19 exons

Exon	Start	End
ENSE00001213593	7070720	7070861
ENSE00001370395	7091472	7091683
ENSE00001494431	7021449	7021537
ENSE00001494433	6995804	6995898
ENSE00001494434	6978213	6978243
ENSE00001494437	6912088	6912172
ENSE00001593786	7090089	7090190
ENSE00001607530	7071560	7071623
ENSE00001654905	7085898	7085972
ENSE00001716749	7071733	7071830
ENSE00001729171	7086290	7086417
ENSE00001731081	7080732	7080853
ENSE00001744765	7074560	7074620
ENSE00001763966	7087267	7087432
ENSE00001793373	7025035	7025142
ENSE00003379331	7070196	7070328
ENSE00003432678	7042980	7043125
ENSE00003437631	7063897	7064149
ENSE00003895757	6910697	6910982

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 86.05.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6709 / max 36.9758, expressed in 184 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201103	0.3843	166
201102	0.1136	74
201101	0.1016	62
201100	0.0715	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.35	gold quality
adrenal tissue	UBERON:0018303	61.74	gold quality
prostate gland	UBERON:0002367	60.29	gold quality
ventricular zone	UBERON:0003053	60.22	gold quality
right lobe of thyroid gland	UBERON:0001119	57.97	gold quality
thyroid gland	UBERON:0002046	55.09	gold quality
ganglionic eminence	UBERON:0004023	54.91	gold quality
metanephros cortex	UBERON:0010533	54.86	gold quality
left lobe of thyroid gland	UBERON:0001120	54.52	gold quality
cortical plate	UBERON:0005343	54.15	gold quality
renal medulla	UBERON:0000362	52.81	gold quality
islet of Langerhans	UBERON:0000006	52.26	gold quality
right lung	UBERON:0002167	52.11	gold quality
minor salivary gland	UBERON:0001830	51.63	gold quality
mucosa of transverse colon	UBERON:0004991	50.56	gold quality
metanephros	UBERON:0000081	50.52	gold quality
mouth mucosa	UBERON:0003729	50.13	gold quality
pancreas	UBERON:0001264	50.01	gold quality
bronchial epithelial cell	CL:0002328	49.93	gold quality
saliva-secreting gland	UBERON:0001044	49.48	gold quality
bronchus	UBERON:0002185	49.47	gold quality
trachea	UBERON:0003126	49.45	gold quality
body of pancreas	UBERON:0001150	49.16	gold quality
gastrocnemius	UBERON:0001388	48.34	gold quality
muscle of leg	UBERON:0001383	47.50	gold quality
right lobe of liver	UBERON:0001114	46.80	gold quality
cortex of kidney	UBERON:0001225	46.61	gold quality
colonic epithelium	UBERON:0000397	45.95	gold quality
kidney	UBERON:0002113	45.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TBL1Y, 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-627-3P	99.90	71.42	3316
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6874-5P	95.73	64.94	545
HSA-MIR-4633-3P	93.85	63.56	534
HSA-MIR-6500-5P	93.85	63.64	522

Literature-anchored findings (GeneRIF, showing 6)

• investigated 12 single-nucleotide polymorphisms in Y-linked neuroligin 4, transducin b-like 1, and eukaryotic translation initiation factor 1a genes, results suggest a Y chromosome effect in autism (PMID:19605777)
• Taken together,these findings suggest that TBL1 controls NF-kB activation by recruiting NF-kB to its target gene promoter. (PMID:21189284)
• Our findings suggest that TBL1Y is involved in the genesis of non-syndromic coarctation of the aorta. (PMID:22280357)
• TBL1 is required to protect GPS2 from degradation, with methylation of GPS2 by arginine methyltransferase PRMT6 regulating the interaction with TBL1 and inhibiting proteasome-dependent degradation. (PMID:26070566)
• reducing TBL1Y cellular level using siRNA approach influenced cardiac differentiation by reducing its efficacy as well as increasing the probability of impaired contractions; proposed reclassification of TBL1Y as “found missing protein” (PMID:28853286)
• TBL1Y mutation causes syndromic hearing loss. Pathogenic variant affects protein expression and stability. (PMID:30341416)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbl1x	ENSDARG00000060438
mus_musculus	Tbl1x	ENSMUSG00000025246
rattus_norvegicus	Tbl1xr1	ENSRNOG00000003686
drosophila_melanogaster	ebi	FBGN0263933

Paralogs (2): TBL1X (ENSG00000101849), TBL1XR1 (ENSG00000177565)

Protein

Protein identifiers

F-box-like/WD repeat-containing protein TBL1Y — Q9BQ87 (reviewed: Q9BQ87)

Alternative names: Transducin beta-like protein 1Y, Transducin-beta-like protein 1, Y-linked

All UniProt accessions (2): Q9BQ87, A0A494C153

UniProt curated annotations — full annotation on UniProt →

Function. F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange.

Subunit / interactions. Probable component of the N-Cor repressor complex and some E3 ubiquitin ligase complex. Interacts with NCOR2.

Subcellular location. Nucleus.

Tissue specificity. Fetal brain and prostate. Expressed in the cochlear spiral ganglion neurons, and in outer and inner hair cells.

Disease relevance. Deafness, Y-linked 2 (DFNY2) [MIM:400047] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNY2 patients show bilateral symmetric hearing loss ranging from mild to severe, with onset in the third to fifth decades of life. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.

Similarity. Belongs to the WD repeat EBI family.

RefSeq proteins (3): NP_150600, NP_599020, NP_599021 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR006594	LisH	Conserved_site
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045183	Ebi-like	Family

Pfam: PF00400, PF08513

UniProt features (17 total): repeat 8, modified residue 3, domain 2, initiator methionine 1, chain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ87-F1	87.15	0.72

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, 102, 130, 287

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 49 (showing top): WHITEHURST_PACLITAXEL_SENSITIVITY, NKX25_02, GCANCTGNY_MYOD_Q6, CEBPB_01, YGACNNYACAR_UNKNOWN, TGCTGAY_UNKNOWN, TGANTCA_AP1_C, NRF2_Q4, PTF1BETA_Q6, NFE2_01, TGGAAA_NFAT_Q4_01, NUYTTEN_EZH2_TARGETS_DN, GOCC_HISTONE_DEACETYLASE_COMPLEX, NUYTTEN_NIPP1_TARGETS_DN, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (2): transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (3): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1923 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBL1Y	NCOR1	O75376	997
TBL1Y	GPS2	Q13227	997
TBL1Y	HDAC3	O15379	994
TBL1Y	TBL1XR1	Q9BZK7	987
TBL1Y	NCOR2	Q9Y618	977
TBL1Y	AMELY	Q99218	931
TBL1Y	PRKY	O43930	926
TBL1Y	CTNNB1	P35222	924
TBL1Y	A0A087WUC5	A0A087WUC5	907
TBL1Y	TSPY1	P09002	897
TBL1Y	AMELX	Q99217	896
TBL1Y	PCDH11X	Q9BZA7	789
TBL1Y	TBL2	Q9Y4P3	661
TBL1Y	USP9Y	O00507	644
TBL1Y	HDAC1	Q13547	625

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NUDC	TBL1Y	psi-mi:“MI:0915”(physical association)	0.400
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TBL1Y	HDAC3	psi-mi:“MI:0914”(association)	0.350
ELF5	ARID1A	psi-mi:“MI:2364”(proximity)	0.270
ETV6	ARHGAP32	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): TBL1Y (Affinity Capture-MS), TBL1Y (Affinity Capture-MS), TBL1X (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), GPS2 (Affinity Capture-MS), NCOR1 (Affinity Capture-MS), HDAC3 (Affinity Capture-MS), CAPN15 (Affinity Capture-MS), INTS6 (Affinity Capture-MS), MAP3K7 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), TAB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: A2QHM1, A2QPW4, A3LNW3, A3LVM1, A5E2R6, A7EZJ5, A7RWD2, A7TLU2, A7YY75, A8IZG4, A8PWQ8, A9VDW7, B0XAF3, B3MC74, B3NQR5, B3RNR8, B4GDM7, B4GMG4, B4HRQ6, B4JW81, B4KTK4, B4LJT7, B4MY77, B4P7Q3, B4QFZ8, B5X212, B5X9P2, B7QKS1, B9WHJ2, G0SA60, O13923, O14186, O22607, O60907, O76071, O80990, O94319, P0CS50, P0CS51, P53011

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TBL1Y	“down-regulates quantity by destabilization”	CTBP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

3793 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:6936843:G:GT	donor_gain	1.0000
Y:6980454:G:GT	donor_gain	1.0000
Y:7021445:CTAGG:C	acceptor_gain	1.0000
Y:7021446:TA:T	acceptor_loss	1.0000
Y:7021446:TAGGC:T	acceptor_gain	1.0000
Y:7021447:A:AG	acceptor_gain	1.0000
Y:7021447:A:C	acceptor_loss	1.0000
Y:7021447:AG:A	acceptor_gain	1.0000
Y:7021447:AGGC:A	acceptor_gain	1.0000
Y:7021447:AGGCT:A	acceptor_gain	1.0000
Y:7021448:G:GA	acceptor_gain	1.0000
Y:7021448:GG:G	acceptor_gain	1.0000
Y:7021448:GGC:G	acceptor_gain	1.0000
Y:7021448:GGCT:G	acceptor_gain	1.0000
Y:7021448:GGCTG:G	acceptor_gain	1.0000
Y:7021537:GGTAA:G	donor_loss	1.0000
Y:7021538:G:GA	donor_loss	1.0000
Y:7021538:G:GG	donor_gain	1.0000
Y:7021539:T:G	donor_loss	1.0000
Y:7042974:CCGCA:C	acceptor_loss	1.0000
Y:7042975:CGCA:C	acceptor_loss	1.0000
Y:7042976:GCAG:G	acceptor_loss	1.0000
Y:7042977:CA:C	acceptor_loss	1.0000
Y:7042978:A:AC	acceptor_loss	1.0000
Y:7043095:G:GG	donor_gain	1.0000
Y:7043124:AGG:A	donor_loss	1.0000
Y:7043126:GT:G	donor_loss	1.0000
Y:7064150:G:GG	donor_gain	1.0000
Y:7070718:A:AG	acceptor_gain	1.0000
Y:7070719:G:GG	acceptor_gain	1.0000

AlphaMissense

3481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:7087350:T:A	V455D	1.000
Y:7086416:A:C	S427R	0.999
Y:7087267:T:A	S427R	0.999
Y:7087267:T:G	S427R	0.999
Y:7087290:G:C	R435P	0.999
Y:7087295:T:A	W437R	0.999
Y:7087295:T:C	W437R	0.999
Y:7087297:G:C	W437C	0.999
Y:7087297:G:T	W437C	0.999
Y:7087421:T:A	W479R	0.999
Y:7087421:T:C	W479R	0.999
Y:7086411:T:C	L425S	0.998
Y:7087269:C:A	A428D	0.998
Y:7087271:T:C	S429P	0.998
Y:7087296:G:C	W437S	0.998
Y:7071774:T:C	F280L	0.997
Y:7071776:C:A	F280L	0.997
Y:7071776:C:G	F280L	0.997
Y:7086414:C:A	A426E	0.997
Y:7087278:A:T	D431V	0.997
Y:7087287:T:A	V434E	0.997
Y:7087293:T:C	L436P	0.997
Y:7087386:T:C	L467S	0.997
Y:7087423:G:C	W479C	0.997
Y:7087423:G:T	W479C	0.997
Y:7070297:T:A	W187R	0.996
Y:7070297:T:C	W187R	0.996
Y:7071786:T:A	W284R	0.996
Y:7071786:T:C	W284R	0.996
Y:7087277:G:C	D431H	0.996

dbSNP variants (sampled 300 via entrez): RS1000088460 (Y:6965517 C>T), RS1000169587 (Y:7073953 C>T), RS1000314547 (Y:7057635 T>C), RS1000345643 (Y:7059163 G>A,C), RS1000413121 (Y:7028312 G>A), RS1000494750 (Y:6931043 C>A,T), RS1000614534 (Y:7103673 C>T), RS1000632064 (Y:6933211 A>G), RS1000728591 (Y:7105281 C>T), RS1000862077 (Y:7035416 C>T), RS1000937848 (Y:7004366 A>G), RS1001147703 (Y:6975492 C>T), RS1001212429 (Y:7072491 C>A), RS1001246054 (Y:6916972 C>T), RS1001412507 (Y:6972503 A>G)

Disease associations

OMIM: gene MIM:400033 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment
HP:0001450	Y-linked inheritance

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010733_2	Autism	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	affects cotreatment, decreases expression	1
arsenite	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Dexamethasone	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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