TUBA3D

tubulin alpha 3d, the group of Tubulins

Basic information

Region (hg38): 2:131476118-131482934

Links

ENSG00000075886 ∙ NCBI:113457 ∙ OMIM:617878 ∙ HGNC:24071 ∙ Uniprot:P0DPH8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• keratoconus 9 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keraconus 9	AD	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	Ophthalmologic	29051577

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBA3D gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBA3D 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				3	1	4
missense			28	1	1	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	28	5	2

Variants in TUBA3D

This is a list of pathogenic ClinVar variants found in the TUBA3D region.

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

Position	Type	Phenotype	Significance	ClinVar
2-131478155-T-G			Likely benign (Mar 29, 2018)
2-131478185-G-A		not specified	Uncertain significance (Jan 03, 2024)
2-131478191-C-T		Keratoconus 9	Pathogenic (Apr 04, 2018)
2-131478261-G-A		not specified	Uncertain significance (Jun 02, 2024)
2-131478293-G-A		not specified	Uncertain significance (May 16, 2024)
2-131478299-G-A		not specified	Uncertain significance (Feb 14, 2023)
2-131478318-T-C		not specified	Uncertain significance (Nov 22, 2021)
2-131478358-G-GTT		Keratoconus 9	Pathogenic (May 08, 2018)
2-131479347-C-T		not specified	Uncertain significance (Dec 17, 2023)
2-131479390-C-T			Likely benign (Dec 31, 2019)
2-131479422-T-A			Benign (Dec 31, 2019)
2-131480123-G-A		not specified	Uncertain significance (Jun 24, 2022)
2-131480159-C-T		Hepatocellular carcinoma	Pathogenic (Jun 15, 2021)
2-131480160-G-A		not specified	Uncertain significance (Sep 16, 2021)
2-131480285-T-C		not specified	Uncertain significance (Nov 17, 2023)
2-131480291-T-C		not specified	Uncertain significance (Jun 21, 2023)
2-131480330-T-C		not specified	Uncertain significance (Dec 11, 2023)
2-131480333-C-T		not specified	Uncertain significance (Mar 31, 2024)
2-131480336-C-T		not specified	Uncertain significance (Dec 27, 2023)
2-131480349-T-C		not specified	Uncertain significance (Oct 27, 2022)
2-131480361-C-A		not specified	Uncertain significance (Feb 27, 2023)
2-131480409-C-T		not specified	Uncertain significance (May 26, 2024)
2-131480451-C-T		not specified	Uncertain significance (Sep 29, 2022)
2-131480492-T-A		not specified	Uncertain significance (Jun 07, 2024)
2-131480542-C-T			Likely benign (Jan 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBA3D	protein_coding	protein_coding	ENST00000321253	5	6842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.24e-10	0.0761	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.53	219	293	0.748	0.0000194	2930
Missense in Polyphen		98	126.1	0.77719		1378
Synonymous	-0.362	126	121	1.04	0.00000844	904
Loss of Function	-0.0266	14	13.9	1.01	6.80e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000449	0.000449
Ashkenazi Jewish	0.00	0.00
East Asian	0.000329	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.000329	0.000326
South Asian	0.000592	0.000588
Other	0.000652	0.000652

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: Keratoconus 9 (KTCN9) [MIM:617928]: An autosomal dominant form of keratoconus, a common degenerative corneal disease characterized by progressive, non-inflammatory thinning of the corneal stroma, corneal ectasia, and cone-shaped corneal protrusion that results in reduced vision. {ECO:0000269|PubMed:29051577}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Phagosome - Homo sapiens (human);Gap junction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Apoptosis - Homo sapiens (human);Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;stathmin and breast cancer resistance to antimicrotubule agents;downregulated of mta-3 in er-negative breast tumors;Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;Formation of tubulin folding intermediates by CCT/TriC;Carboxyterminal post-translational modifications of tubulin;Protein folding;Prefoldin mediated transfer of substrate to CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;Post-chaperonin tubulin folding pathway (Consensus)

Recessive Scores

• pRec: 0.292

Intolerance Scores

• loftool: 0.443
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.502
• hipred: N
• hipred_score: 0.300
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.358

Gene Damage Prediction

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

Gene ontology

• Biological process: cytoskeleton organization;microtubule-based process
• Cellular component: cytoplasm;microtubule
• Molecular function: GTPase activity;structural constituent of cytoskeleton;GTP binding