TBCE

tubulin folding cofactor E

Basic information

Region (hg38): 1:235367359-235452443

Previous symbols: [ "KCS", "HRD" ]

Links

ENSG00000284770 ∙ NCBI:6905 ∙ OMIM:604934 ∙ HGNC:11582 ∙ Uniprot:Q15813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypoparathyroidism-retardation-dysmorphism syndrome (Definitive), mode of inheritance: AR
• autosomal recessive Kenny-Caffey syndrome (Moderate), mode of inheritance: AR
• hypoparathyroidism-retardation-dysmorphism syndrome (Supportive), mode of inheritance: AR
• autosomal recessive Kenny-Caffey syndrome (Supportive), mode of inheritance: AR
• encephalopathy, progressive, with amyotrophy and optic atrophy (Limited), mode of inheritance: AR
• hypoparathyroidism-retardation-dysmorphism syndrome (Strong), mode of inheritance: AR
• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kenny-Caffey syndrome, type 1; Hypoparathyroidism-retardation-dysmorphism syndrome	AR	Endocrine	Individuals can present with sequelae of neonatal hypocalcemia, and prompt diagnosis and treatment can lead to correction of electrolyte abnormalities; Some individuals with multiple pituitary anomalies (eg, affecting GH, cortisol, and including features of hypogonadotropic hypogonadism have been described), and surveillance may allow early diagnosis and treatment	Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	2843457; 1701077; 2001103; 1308349; 7538982; 9056548; 12389028; 19491227; 19554981; 27666369

ClinVar

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

• not provided (348 variants)
• Hypoparathyroidism-retardation-dysmorphism syndrome (60 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (30 variants)
• Inborn genetic diseases (22 variants)
• not specified (17 variants)
• Encephalopathy, progressive, with amyotrophy and optic atrophy (10 variants)
• Autosomal recessive Kenny-Caffey syndrome (4 variants)
• Hypoparathyroidism-retardation-dysmorphism syndrome;Autosomal recessive Kenny-Caffey syndrome;Encephalopathy, progressive, with amyotrophy and optic atrophy (2 variants)
• Hypoparathyroidism-retardation-dysmorphism syndrome;Autosomal recessive Kenny-Caffey syndrome (2 variants)
• TBCE-Related Disorder (1 variants)
• Hypoparathyroidism-retardation-dysmorphism syndrome;Encephalopathy, progressive, with amyotrophy and optic atrophy;Autosomal recessive Kenny-Caffey syndrome (1 variants)
• Microcephaly (1 variants)
• - (1 variants)
• See cases (1 variants)
• Disorder of sexual differentiation (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• TBCE-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBCE 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			5	55	3	63
missense		3	77	8	2	90
nonsense	7	1				8
start loss			1			1
frameshift	4	4	3			11
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)		3	1			4
splice region			10	11	2	23
non coding		1	37	79	68	185
Total	11	13	127	142	73

Highest pathogenic variant AF is 0.0000131

Variants in TBCE

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

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

Position	Type	Phenotype	Significance	ClinVar
1-235367443-T-A		Hypoparathyroidism-retardation-dysmorphism syndrome	Likely benign (Apr 27, 2017)
1-235367444-C-G		Hypoparathyroidism-retardation-dysmorphism syndrome	Uncertain significance (Jan 12, 2018)
1-235367468-G-C		Hypoparathyroidism-retardation-dysmorphism syndrome	Uncertain significance (Jan 12, 2018)
1-235367487-T-C		Hypoparathyroidism-retardation-dysmorphism syndrome	Benign (Aug 10, 2021)
1-235379947-C-CA			Benign (Dec 04, 2020)
1-235380051-T-A		not specified	Uncertain significance (May 22, 2023)
1-235380056-G-T		Inborn genetic diseases	Uncertain significance (Feb 17, 2023)
1-235380069-CG-C			Pathogenic (Nov 28, 2023)
1-235380070-G-A		TBCE-related disorder	Likely benign (Jan 04, 2024)
1-235380082-T-C			Likely benign (Jan 14, 2024)
1-235380084-G-A			Uncertain significance (Jul 12, 2022)
1-235380100-T-C			Likely benign (May 14, 2023)
1-235380107-C-T			Uncertain significance (Jan 20, 2022)
1-235380114-CAG-C		Hypoparathyroidism-retardation-dysmorphism syndrome	Pathogenic (Jun 28, 2018)
1-235380119-C-T		Hypoparathyroidism-retardation-dysmorphism syndrome	Uncertain significance (Jan 12, 2018)
1-235380120-G-A		Encephalopathy, progressive, with amyotrophy and optic atrophy • Hypoparathyroidism-retardation-dysmorphism syndrome;Autosomal recessive Kenny-Caffey syndrome;Encephalopathy, progressive, with amyotrophy and optic atrophy	Uncertain significance (May 17, 2022)
1-235380124-T-C			Likely benign (Oct 22, 2023)
1-235380132-T-G			Uncertain significance (Apr 23, 2021)
1-235380138-C-T		Pituitary stalk interruption syndrome	Uncertain significance (Sep 10, 2022)
1-235380142-C-G			Likely benign (Jan 22, 2024)
1-235380142-C-T			Likely benign (Dec 03, 2023)
1-235380150-G-A		Hypoparathyroidism-retardation-dysmorphism syndrome • Autosomal recessive Kenny-Caffey syndrome • Disorder of sexual differentiation • TBCE-related disorder	Conflicting classifications of pathogenicity (Jan 14, 2024)
1-235380155-C-T		TBCE-related disorder	Conflicting classifications of pathogenicity (Aug 31, 2022)
1-235380158-TTATTG-T			Likely benign (Jan 05, 2024)
1-235380158-TTATTGTG-T			Likely benign (Jul 13, 2023)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tubulin-folding protein; involved in the second step of the tubulin folding pathway and in the regulation of tubulin heterodimer dissociation. Required for correct organization of microtubule cytoskeleton and mitotic splindle, and maintenance of the neuronal microtubule network. {ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:27666369}.
• Disease: DISEASE: Hypoparathyroidism-retardation-dysmorphism syndrome (HRDS) [MIM:241410]: An autosomal recessive multisystem disorder characterized by hypoparathyroidism, intrauterine and postnatal growth retardation, psychomotor retardation, epilepsy, microcephaly, and facial dysmorphism. {ECO:0000269|PubMed:12389028}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Kenny-Caffey syndrome 1 (KCS1) [MIM:244460]: An autosomal recessive form of Kenny-Caffey syndrome, a disorder characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. Clinical features include cortical thickening and medullary stenosis of the tubular bones, delayed closure of fontanels, defective dentition, small eyes with hypermetropia, and frontal bossing with a triangular face. {ECO:0000269|PubMed:12389028}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Encephalopathy, progressive, with amyotrophy and optic atrophy (PEAMO) [MIM:617207]: An autosomal recessive, progressive, neurodegenerative encephalopathy with onset in infancy. Affected individuals manifest delayed psychomotor development, severe hypotonia, motor regression, spinal muscular atrophy, distal amyotrophy and weakness of all limbs, and intellectual disability of variable severity. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy. {ECO:0000269|PubMed:27666369}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of proteins;Protein folding;Post-chaperonin tubulin folding pathway (Consensus)

Recessive Scores

• pRec: 0.348

Intolerance Scores

• loftool: 0.901
• rvis_EVS: 0.8
• rvis_percentile_EVS: 87.66

Haploinsufficiency Scores

• pHI: 0.104
• hipred: N
• hipred_score: 0.242

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.281

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbce
• Phenotype: muscle phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: microtubule cytoskeleton organization;protein folding;post-chaperonin tubulin folding pathway;mitotic spindle organization
• Cellular component: cytoplasm;microtubule
• Molecular function: protein binding;chaperone binding