TUB

TUB bipartite transcription factor

Basic information

Region (hg38): 11:8019244-8106243

Links

ENSG00000166402 ∙ NCBI:7275 ∙ OMIM:601197 ∙ HGNC:12406 ∙ Uniprot:P50607 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinal dystrophy and obesity (Moderate), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinal dystrophy and obesity (Limited), mode of inheritance: AR
• essential tremor (Limited), mode of inheritance: AD
• retinal dystrophy and obesity (Limited), mode of inheritance: AR
• retinal dystrophy and obesity (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinal dystrophy and obesity	AR	General	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	Endocrine; Ophthalmologic	24375934

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUB gene.

• not provided (7 variants)
• Retinal dystrophy and obesity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	110	8	120
missense			218	5	2	225
nonsense	3		4			7
start loss			2			2
frameshift	4		2	1		7
inframe indel			9			9
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			14	19	1	34
non coding			2	62	7	71
Total	8	2	240	178	17

Highest pathogenic variant AF is 0.0000197

Variants in TUB

This is a list of pathogenic ClinVar variants found in the TUB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-8038866-T-G		Retinal dystrophy	Uncertain significance (Jan 01, 2023)
11-8038870-C-T		TUB-related disorder	Likely benign (Feb 20, 2024)
11-8038873-G-A		TUB-related disorder	Likely benign (Jun 24, 2021)
11-8038874-A-T			Uncertain significance (Aug 07, 2022)
11-8038876-G-T			Uncertain significance (May 30, 2022)
11-8038877-G-A			Uncertain significance (Jun 24, 2021)
11-8038877-G-GGGGC			Uncertain significance (Jul 20, 2021)
11-8038880-G-A		TUB-related disorder	Uncertain significance (Feb 19, 2024)
11-8038881-C-G		TUB-related disorder	Uncertain significance (Dec 15, 2023)
11-8038906-G-T		TUB-related disorder	Uncertain significance (Mar 05, 2024)
11-8038907-GTTTC-G		TUB-related disorder	Conflicting classifications of pathogenicity (May 24, 2024)
11-8038911-C-T			Uncertain significance (Mar 20, 2022)
11-8038921-C-T			Likely benign (Sep 22, 2023)
11-8038921-CGAGACAGG-C		TUB-related disorder	Uncertain significance (Oct 24, 2022)
11-8038922-G-A		TUB-related disorder	Uncertain significance (Mar 25, 2022)
11-8038922-G-T			Uncertain significance (Aug 21, 2022)
11-8038924-G-C		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
11-8038925-A-G			Uncertain significance (Jun 04, 2022)
11-8038936-G-A		TUB-related disorder	Likely benign (Oct 29, 2023)
11-8038941-C-T		TUB-related disorder	Uncertain significance (Feb 05, 2022)
11-8038946-G-C		TUB-related disorder	Uncertain significance (Mar 06, 2022)
11-8038954-C-T			Likely benign (Jun 14, 2022)
11-8038956-G-C		TUB-related disorder	Uncertain significance (Feb 27, 2022)
11-8038958-C-T			Uncertain significance (May 19, 2021)
11-8038960-C-A			Likely benign (Mar 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUB	protein_coding	protein_coding	ENST00000305253	13	86869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00315	0.997	125714	0	33	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.470	331	356	0.930	0.0000227	3655
Missense in Polyphen		135	165.29	0.81676		1697
Synonymous	-1.48	157	135	1.16	0.00000841	1109
Loss of Function	3.41	10	30.2	0.331	0.00000175	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000416	0.000416
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.00	0.00
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.00	0.00
South Asian	0.000165	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions in signal transduction from heterotrimeric G protein-coupled receptors. Binds to membranes containing phosphatidylinositol 4,5-bisphosphate. Can bind DNA (in vitro). May contribute to the regulation of transcription in the nucleus. Could be involved in the hypothalamic regulation of body weight (By similarity). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages. {ECO:0000250, ECO:0000269|PubMed:19837063}.
• Disease: DISEASE: Retinal dystrophy and obesity (RDOB) [MIM:616188]: A disease characterized by obesity, night blindness, decreased visual acuity, and electrophysiological features of a rod cone dystrophy. {ECO:0000269|PubMed:24375934}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: g-protein signaling through tubby proteins (Consensus)

Recessive Scores

• pRec: 0.253

Intolerance Scores

• loftool: 0.0654
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.544
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.726

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tub
• Phenotype: vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; pigmentation phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: phagocytosis, recognition;sensory perception of sound;response to hormone;photoreceptor cell maintenance;positive regulation of phagocytosis;retina development in camera-type eye;protein localization to cilium;receptor localization to non-motile cilium;protein localization to photoreceptor outer segment
• Cellular component: extracellular region;nucleus;cytoplasm;cytosol;plasma membrane;cilium
• Molecular function: phosphatidylinositol binding;protein-containing complex binding