TBL1Y

protein-coding

transducin beta like 1 Y-linked, the group of WD repeat domain containing

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_033284.2

Inheritance

ClinVar variants

U:34B:7

Top phenotype

Deafness, Y-linked 2

gnomAD constraint

pLI —, LoF o/e 1.82

Max pathogenic AF

—

Genomic locus

chrY:6,910,686-7,101,970

External References & Databases

Ensembl (ENSG00000092377)

Transcript & Mutation Effects

hg38 • Region Span ~191.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Deafness, Y-linked 2YL

Manifestation: Audiologic/Otolaryngologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30341416

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBL1Y variants in ClinVar

4 Conditions Cataloged

TBL1Y-related disorderTotal: 4

not specifiedTotal: 4

not providedTotal: 2

Deafness, Y-linked 2Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033284.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	2 clinvar		11
missense			17 clinvar	4 clinvar		21
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar	1 clinvar		7
Total	0	0	34	7	0	41

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033284.2	RefSeq	NP_150600.1	14	MANE Select
ENST00000383032.6	Ensembl	ENSP00000372499.1	14	MANE Select
NM_134258.2	RefSeq	NP_599020.1	14	Standard
NM_134259.2	RefSeq	NP_599021.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt signaling pathway - Homo sapiens (human)

Biological Process

regulation of transcription by RNA polymerase II
histone deacetylation
negative regulation of nucleic acid-templated transcription

Molecular Function

transcription corepressor activity

Cellular Component

histone deacetylase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000383032
Coding exons: 14
Length: 180998
Individuals with no LoFs: 67690
Homozygous LoFs: 127
Heterozygous LoFs: 0
Defined: 67817
p: 0.000937

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.77	183	85.2	2.15	0.0000138	3474
Missense (PolyPhen)		85	44.736	1.9		1777
Synonymous	-4.76	72	35.8	2.01	0.00000633	975
Loss of Function	-2.18	15	8.24	1.82	0.00000127	324

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0023	0.0011	notable
Latino/Admixed American	0.0011	0.00056	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.017	0.0086	notable
Finnish	0.00072	0.00035	rare
European (Non-Finnish)	0.00059	0.00028	rare
South Asian	0.00044	0.00022	rare
Other	0.0044	0.0022	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.119

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium