TBCK

TBC1 domain containing kinase

Basic information

Region (hg38): 4:106041599-106316683

Links

ENSG00000145348NCBI:93627OMIM:616899HGNC:28261Uniprot:Q8TEA7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic25558065; 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
clinvar
140
clinvar
7
clinvar
149
missense
2
clinvar
2
clinvar
285
clinvar
9
clinvar
6
clinvar
304
nonsense
14
clinvar
7
clinvar
21
start loss
1
clinvar
1
frameshift
22
clinvar
8
clinvar
30
inframe indel
6
clinvar
6
splice donor/acceptor (+/-2bp)
6
clinvar
14
clinvar
1
clinvar
21
splice region
23
35
8
66
non coding
5
clinvar
120
clinvar
49
clinvar
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)2070160
4-106046576-T-C Likely benign (Nov 06, 2022)2812464
4-106046577-T-G Uncertain significance (Sep 26, 2021)1360721
4-106046581-G-A Inborn genetic diseases Uncertain significance (Dec 10, 2024)1401765
4-106046583-G-A Uncertain significance (Aug 19, 2022)1519297
4-106046585-T-C Likely benign (Mar 11, 2023)1963730
4-106046592-G-A Benign (Jan 15, 2024)736370
4-106046593-T-G Uncertain significance (Aug 14, 2021)1367336
4-106046610-T-C Uncertain significance (Feb 28, 2022)2104235
4-106046619-T-C Uncertain significance (Jul 12, 2022)1481375
4-106046635-G-A Likely benign (Mar 12, 2022)2109659
4-106046651-A-G Likely benign (Dec 25, 2022)2824098
4-106046664-A-G Inborn genetic diseases Uncertain significance (May 23, 2023)1470654
4-106046675-T-C Likely benign (Jan 22, 2023)2977064
4-106046678-A-C Uncertain significance (May 06, 2022)2134564
4-106046684-GA-G TBCK-related disorder Benign (May 28, 2024)1925237
4-106046684-G-GA Benign (Dec 16, 2023)1599218
4-106046687-A-G Likely benign (Dec 12, 2024)1540746
4-106046690-A-T Likely benign (Aug 16, 2024)1902294
4-106046695-A-G Likely benign (Dec 22, 2024)1633035
4-106046696-G-A Likely benign (Nov 06, 2024)3610318
4-106095465-T-A Likely benign (Nov 25, 2024)1670052
4-106095473-T-C Likely benign (Oct 06, 2023)2167072
4-106095483-T-C Uncertain significance (Aug 23, 2022)2132010
4-106095511-C-T Inborn genetic diseases Uncertain significance (Jan 06, 2025)1508750

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TBCKprotein_codingprotein_codingENST00000273980 25279897
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
2.09e-150.9401256620861257480.000342
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5034184480.9330.00002215832
Missense in Polyphen98131.750.743831727
Synonymous0.07501611620.9930.000008201691
Loss of Function2.283148.00.6450.00000249638

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007070.000699
Ashkenazi Jewish0.000.00
East Asian0.0002880.000272
Finnish0.0001390.000139
European (Non-Finnish)0.0004460.000440
Middle Eastern0.0002880.000272
South Asian0.0002710.000261
Other0.0001790.000163

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

loftool
rvis_EVS
-0.04
rvis_percentile_EVS
50.5

Haploinsufficiency Scores

pHI
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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tbck
Phenotype

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