TUBB1

Chr 20AD

tubulin beta 1 class VI

Also known as: MACTHC1

This gene encodes a member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is specifically expressed in platelets and megakaryocytes and may be involved in proplatelet production and platelet release. A mutations in this gene is associated with autosomal dominant macrothrombocytopenia. Two pseudogenes of this gene are found on chromosome Y.[provided by RefSeq, Jul 2010]

OMIMResearchGenerating clinical summary…
DNmechanismADLOEUF 1.351 OMIM phenotype
Clinical SummaryTUBB1
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Gene-Disease Validity (ClinGen)
macrothrombocytopenia, isolated, 1, autosomal dominant · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 202 VUS of 337 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.35LOEUF
pLI 0.000
Z-score 0.58
OE 0.83 (0.531.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.00Z-score
OE missense 1.00 (0.901.10)
272 obs / 272.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.83 (0.531.35)
00.351.4
Missense OE?1.00 (0.901.10)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 12 / 14.4Missense obs/exp: 272 / 272.1Syn Z: -0.25

This gene — mechanism propensity

DN
0.7227th %ile
GOF
0.3590th %ile
LOF
0.3259th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

337 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic14
VUS202
Likely Benign74
Benign15
Conflicting24
3
Pathogenic
14
Likely Pathogenic
202
VUS
74
Likely Benign
15
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
0
0
3
Likely Pathogenic
9
4
1
0
14
VUS
15
182
4
1
202
Likely Benign
0
6
14
54
74
Benign
0
5
3
7
15
Conflicting
24
Total261982262332

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap TUBB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TUBB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →