TUBA3D

protein-coding

tubulin alpha 3d, the group of Tubulins

Gene summary

This gene encodes a member of the alpha tubulin family. Tubulin is a major component of microtubules, which are composed of alpha- and beta-tubulin heterodimers and microtubule-associated proteins in the cytoskeleton. Microtubules maintain cellular structure, function in intracellular transport, and play a role in spindle formation during mitosis. [provided by RefSeq, Oct 2011]

MANE transcript

NM_080386.4

Inheritance

ClinVar variants

P:2U:63B:11

Top phenotype

Keraconus 9

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr2:131,476,119-131,482,934

External References & Databases

Ensembl (ENSG00000075886)

Transcript & Mutation Effects

hg38 • Region Span ~6.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

keratoconus 9LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0054771

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Keraconus 9AD

Manifestation: Ophthalmologic

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: 29051577

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUBA3D variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 11

Keratoconus 9Total: 7

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080386.4. 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				4 clinvar	3 clinvar	7
missense			62 clinvar	3 clinvar	1 clinvar	66
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	2	0	63	7	4	76

Highest pathogenic variant AF is 0.000008055352

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080386.4	RefSeq	NP_525125.2	5	MANE Select
ENST00000321253.7	Ensembl	ENSP00000326042.6	5	MANE Select
ENST00001090547.1	Ensembl	ENSP00000760353.1	4	Standard
ENST00001139251.1	Ensembl	ENSP00000807016.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

cytoskeleton organization
microtubule-based process

Molecular Function

GTPase activity
structural constituent of cytoskeleton
GTP binding

Cellular Component

cytoplasm
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321253
Coding exons: 5
Length: 6842
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.53	219	293	0.748	0.0000194	2930
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00059	0.00059	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.292

Intolerance Scores

LoFtool: 0.443
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.358

Gene Damage Prediction

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