TBCK

TBC1 domain containing kinase

Basic information

Region (hg38): 4:106041599-106316683

Links

ENSG00000145348 ∙ NCBI:93627 ∙ OMIM:616899 ∙ HGNC:28261 ∙ Uniprot:Q8TEA7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3	AR	General	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	Craniofacial; Neurologic	25558065; 27040691; 27040692

ClinVar

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

• not provided (34 variants)
• Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (18 variants)
• Inborn genetic diseases (3 variants)
• TBCK-related disorder (3 variants)
• Syndromic Infantile Encephalopathy (2 variants)
• 6 conditions (1 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBCK 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			2	140	7	149
missense	2	2	285	9	6	304
nonsense	14	7				21
start loss			1			1
frameshift	22	8				30
inframe indel			6			6
splice donor/acceptor (+/-2bp)	6	14	1			21
splice region			23	35	8	66
non coding			5	120	49	174
Total	44	31	300	269	62

Highest pathogenic variant AF is 0.000238

Variants in TBCK

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

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

Position	Type	Phenotype	Significance	ClinVar
4-106046573-T-A			Likely benign (Jan 05, 2022)
4-106046576-T-C			Likely benign (Nov 06, 2022)
4-106046577-T-G			Uncertain significance (Sep 26, 2021)
4-106046581-G-A		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
4-106046583-G-A			Uncertain significance (Aug 19, 2022)
4-106046585-T-C			Likely benign (Mar 11, 2023)
4-106046592-G-A			Benign (Jan 15, 2024)
4-106046593-T-G			Uncertain significance (Aug 14, 2021)
4-106046610-T-C			Uncertain significance (Feb 28, 2022)
4-106046619-T-C			Uncertain significance (Jul 12, 2022)
4-106046635-G-A			Likely benign (Mar 12, 2022)
4-106046651-A-G			Likely benign (Dec 25, 2022)
4-106046664-A-G		Inborn genetic diseases	Uncertain significance (May 23, 2023)
4-106046675-T-C			Likely benign (Jan 22, 2023)
4-106046678-A-C			Uncertain significance (May 06, 2022)
4-106046684-GA-G		TBCK-related disorder	Benign (May 28, 2024)
4-106046684-G-GA			Benign (Dec 16, 2023)
4-106046687-A-G			Likely benign (Dec 12, 2024)
4-106046690-A-T			Likely benign (Aug 16, 2024)
4-106046695-A-G			Likely benign (Dec 22, 2024)
4-106046696-G-A			Likely benign (Nov 06, 2024)
4-106095465-T-A			Likely benign (Nov 25, 2024)
4-106095473-T-C			Likely benign (Oct 06, 2023)
4-106095483-T-C			Uncertain significance (Aug 23, 2022)
4-106095511-C-T		Inborn genetic diseases	Uncertain significance (Jan 06, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBCK	protein_coding	protein_coding	ENST00000273980	25	279897

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.09e-15	0.940	125662	0	86	125748	0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.503	418	448	0.933	0.0000221	5832
Missense in Polyphen		98	131.75	0.74383		1727
Synonymous	0.0750	161	162	0.993	0.00000820	1691
Loss of Function	2.28	31	48.0	0.645	0.00000249	638

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000707	0.000699
Ashkenazi Jewish	0.00	0.00
East Asian	0.000288	0.000272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000446	0.000440
Middle Eastern	0.000288	0.000272
South Asian	0.000271	0.000261
Other	0.000179	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the modulation of mTOR signaling and expression of mTOR complex components (PubMed:27040691, PubMed:23977024). Involved in the regulation of cell proliferation and growth (PubMed:23977024, PubMed:24576458). Involved in the control of actin-cytoskeleton organization (PubMed:23977024). {ECO:0000269|PubMed:23977024, ECO:0000269|PubMed:24576458, ECO:0000269|PubMed:27040691}.
• Disease: DISEASE: Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 (IHPRF3) [MIM:616900]: An autosomal recessive neurodevelopmental disorder characterized by profound developmental disability, intellectual disability and severe hypotonia. Many patients have seizures, and show brain atrophy, dysgenesis of the corpus callosum and white-matter changes on neuroimaging. Non-specific facial dysmorphism is noted in some individuals. {ECO:0000269|PubMed:25558065, ECO:0000269|PubMed:27040691, ECO:0000269|PubMed:27040692}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -0.04
• rvis_percentile_EVS: 50.5

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.492
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbck

Gene ontology

• Biological process: protein phosphorylation;intracellular protein transport;cell population proliferation;actin cytoskeleton organization;regulation of TOR signaling;activation of GTPase activity
• Cellular component: cytoplasm;midbody;mitotic spindle
• Molecular function: protein kinase activity;GTPase activator activity;ATP binding;Rab GTPase binding