TUBB4B

tubulin beta 4B class IVb, the group of Tubulins

Basic information

Region (hg38): 9:137241287-137243707

Previous symbols: [ "TUBB2C" ]

Links

ENSG00000188229 ∙ NCBI:10383 ∙ OMIM:602660 ∙ HGNC:20771 ∙ Uniprot:P68371 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis with early-onset deafness (Strong), mode of inheritance: AD
• Leber congenital amaurosis with early-onset deafness (Strong), mode of inheritance: AD
• Leber congenital amaurosis with early-onset deafness (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis with early-onset deafness	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	29198720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBB4B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB4B 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				68	8	76
missense		2	11			13
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	7	2	11
non coding				8	6	14
Total	0	2	13	76	14

Variants in TUBB4B

This is a list of pathogenic ClinVar variants found in the TUBB4B region.

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

Position	Type	Phenotype	Significance	ClinVar
9-137241299-G-T			Benign (May 25, 2021)
9-137241332-C-A			Benign (May 25, 2021)
9-137241340-CCCG-C		TUBB4B-related disorder	Benign (Nov 01, 2024)
9-137241340-CCCGCCGCCG-C		TUBB4B-related disorder	Likely benign (Nov 25, 2020)
9-137241340-C-CCCGCCG		TUBB4B-related disorder	Likely benign (Jan 08, 2024)
9-137241372-C-T		TUBB4B-related disorder	Benign (Jul 06, 2023)
9-137241378-C-T			Likely benign (Dec 15, 2023)
9-137241379-T-G		not specified	Uncertain significance (May 04, 2022)
9-137241387-C-T			Likely benign (Dec 22, 2023)
9-137241408-C-A			Likely benign (May 23, 2023)
9-137241427-C-T			Benign (Jun 06, 2023)
9-137241432-C-T			Likely benign (Oct 25, 2022)
9-137241705-C-T			Likely benign (Nov 20, 2023)
9-137241714-C-T			Likely benign (Jun 07, 2023)
9-137241716-T-TG			Likely benign (Dec 16, 2023)
9-137241718-T-C			Uncertain significance (Sep 25, 2023)
9-137241723-T-C			Likely benign (Jun 10, 2023)
9-137241739-G-C			Likely pathogenic (Mar 09, 2022)
9-137241747-C-T			Likely benign (Jan 01, 2023)
9-137241771-C-T			Likely benign (Oct 26, 2022)
9-137241774-C-T			Likely benign (Sep 23, 2023)
9-137241780-C-T			Likely benign (Nov 27, 2023)
9-137241783-C-T		TUBB4B-related disorder	Likely benign (Dec 22, 2023)
9-137241786-C-T			Benign (Feb 01, 2023)
9-137241801-C-T			Likely benign (Nov 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBB4B	protein_coding	protein_coding	ENST00000340384	4	2495

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.809	0.191	125444	0	3	125447	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.50	66	276	0.239	0.0000174	2955
Missense in Polyphen		15	121.34	0.12362		1379
Synonymous	-9.11	245	119	2.06	0.00000851	872
Loss of Function	3.00	2	14.2	0.141	6.19e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000893	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
• Disease: DISEASE: Leber congenital amaurosis with early-onset deafness (LCAEOD) [MIM:617879]: An autosomal dominant disease characterized by severe retinal degeneration and sensorineural hearing loss. Symptoms occur within the first decade of life. Onset at birth is observed in some patients. {ECO:0000269|PubMed:29198720}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phagosome - Homo sapiens (human);Gap junction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;Neutrophil degranulation;Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;Formation of tubulin folding intermediates by CCT/TriC;Innate Immune System;Immune System;Carboxyterminal post-translational modifications of tubulin;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Protein folding;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Prefoldin mediated transfer of substrate to CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;Post-chaperonin tubulin folding pathway;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• rvis_EVS: -1
• rvis_percentile_EVS: 8.32

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.565
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tubb4b

Zebrafish Information Network

• Gene name: tubb4b
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;mitotic cell cycle;microtubule-based process;regulation of G2/M transition of mitotic cell cycle;natural killer cell mediated cytotoxicity;neutrophil degranulation;ciliary basal body-plasma membrane docking
• Cellular component: extracellular region;nucleus;cytoplasm;cytosol;cytoskeleton;microtubule;azurophil granule lumen;myelin sheath;extracellular exosome;extracellular vesicle
• Molecular function: double-stranded RNA binding;GTPase activity;structural constituent of cytoskeleton;GTP binding;MHC class I protein binding;unfolded protein binding