TBCD

Chr 17AR

tubulin folding cofactor D

Also known as: PEBAT, SSD-1, tfcD

Cofactor D functions as a tubulin-folding protein required for beta-tubulin assembly and microtubule dynamics, and is essential for mitotic spindle assembly and neuron morphogenesis. Biallelic mutations cause autosomal recessive progressive encephalopathy with early onset, brain atrophy, and thin corpus callosum. This gene is highly constrained against loss-of-function variants (LOEUF 0.493), indicating that heterozygous loss alone is likely detrimental.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.491 OMIM phenotype
Clinical SummaryTBCD
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Gene-Disease Validity (ClinGen)
early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.000
Z-score 5.11
OE 0.36 (0.260.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.82Z-score
OE missense 0.81 (0.750.86)
573 obs / 709.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.260.49)
00.351.4
Missense OE0.81 (0.750.86)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 26 / 73.1Missense obs/exp: 573 / 709.8Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTBCD-related early-onset neurodegenerative encephalopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6550th %ile
GOF
0.5954th %ile
LOF
0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TBCD · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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