TBCE

Chr 1AR

tubulin folding cofactor E

Also known as: HRD, KCS, KCS1, PEAMO, pac2

Cofactor E binds to the cofactor D/beta-tubulin complex and facilitates the release of correctly folded beta-tubulin committed to the native state, functioning as part of the tubulin folding pathway. Biallelic mutations cause autosomal recessive conditions including progressive encephalopathy with amyotrophy and optic atrophy, hypoparathyroidism-retardation-dysmorphism syndrome, and Kenny-Caffey syndrome type 1. The pathogenic mechanism appears to be dominant negative, disrupting proper microtubule formation essential for cellular structure and function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.813 OMIM phenotypes
Clinical SummaryTBCE
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Gene-Disease Validity (ClinGen)
encephalopathy, progressive, with amyotrophy and optic atrophy · ARModerate

Moderate evidence — consider for supplementary testing

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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.44
OE 0.54 (0.370.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.12Z-score
OE missense 0.98 (0.891.08)
276 obs / 281.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.370.81)
00.351.4
Missense OE0.98 (0.891.08)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 18 / 33.2Missense obs/exp: 276 / 281.7Syn Z: -0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTBCE-related hypoparathyroidism-retardation-dysmorphism syndromeLOFAR
strongTBCE-related early-onset progressive encephalopathy with distal spinal muscular atrophyOTHERAR

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

DN
0.6938th %ile
GOF
0.5955th %ile
LOF
0.2679th %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

TBCE · 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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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗