TBCK TBC1 domain containing kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: TBCKprovided by HGNC
Official Full Name: TBC1 domain containing kinaseprovided by HGNC
Primary source: HGNC:HGNC:28261
See related: Ensembl:ENSG00000145348 MIM:616899; AllianceGenome:HGNC:28261
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: Fy-1; TBCKL; FERRY1; IHPRF3; HSPC302
Summary: This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Expression: Ubiquitous expression in ovary (RPKM 5.5), thyroid (RPKM 5.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q24

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (106041599..106316683, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (109352697..109627755, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (106962756..107237840, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mutation Of TBC1 Domain Containing Kinase (TBCK) With Associated Intellectual Disability And Hypotonia.
Title: Mutation Of TBC1 Domain Containing Kinase (TBCK) With Associated Intellectual Disability And Hypotonia.
Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.
Title: Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.
TBCK syndrome: a rare multi-organ neurodegenerative disease.
Title: TBCK syndrome: a rare multi-organ neurodegenerative disease.
Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.
Title: Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.
A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.
Title: A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.
These findings suggest that miR-1208 acts as a tumor suppressor and targets TBCK directly, thus possessing great potential for use in renal cancer therapy.
Title: MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells.
Evidence that TBC1 domain-containing kinase (TBCK) deficiency disorder associated with homozygous TBCK mutations is a novel type of lysosomal storage disease.
Title: Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)?
A novel TBCK mutation was identified in two siblings with infantile hypotonia, psychomotor retardation and characteristic facies type 3.
Title: Further delineation of TBCK - Infantile hypotonia with psychomotor retardation and characteristic facies type 3.
TBCK-encephaloneuronopathy is a clinically distinguishable syndrome with progressive central and peripheral nervous system dysfunction, consistently observed in patients with the TBCK mutation
Title: Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy.
We conclude that the c.1854delT variant in the TBCK gene is the mutation causing the congenital brain abnormality in an Arab-Moslem family from northern Israel.
Title: TBCK-related intellectual disability syndrome: Case study of two patients.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 MedGen: C5567480 OMIM: 616900 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-59799 (e-PCR)
- UniSTS:15637

SHGC-18917 (e-PCR)
- UniSTS:4374

SHGC-50939 (e-PCR)
- UniSTS:63002

SHGC-50491 (e-PCR)
- UniSTS:3367

SHGC-67977 (e-PCR)
- UniSTS:13368

SHGC-18815 (e-PCR)
- UniSTS:37713

SHGC-83528 (e-PCR)
- UniSTS:101740

SHGC-67790 (e-PCR)
- UniSTS:73346

SHGC-106067 (e-PCR)
- UniSTS:169649

SHGC-24739 (e-PCR)
- UniSTS:5841

SHGC-59821 (e-PCR)
- UniSTS:5846

WI-11631 (e-PCR)
- UniSTS:47839

SHGC-57456 (e-PCR)
- UniSTS:46570

RH103971 (e-PCR)
- UniSTS:98296

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	NAS Non-traceable Author Statement more info	PubMed
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in mitotic spindle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: TBC domain-containing protein kinase-like protein

Names: FERRY endosomal RAB5 effector complex subunit 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_034057.3 RefSeqGene

Range

5475..280085

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_836

mRNA and Protein(s)

NM_001163435.3 → NP_001156907.2 TBC domain-containing protein kinase-like protein isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1 and 2 encode the same isoform.

Source sequence(s)

AC093680, AC107381, AC109361, AC114734

Consensus CDS

CCDS54788.1

UniProtKB/Swiss-Prot

B9A6J1, Q4W5B3, Q4W5E1, Q6NUP4, Q8N7M8, Q8TEA7, Q8WW57, Q96GV6, Q9P080

Related

ENSP00000378198.2, ENST00000394708.7

Conserved Domains (3) summary

smart00164
Location:467 → 671

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:43 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:771 → 882

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...
NM_001163436.4 → NP_001156908.2 TBC domain-containing protein kinase-like protein isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).

Source sequence(s)

AC109361, AC114734, AI279137, AK074305, DB223368

Consensus CDS

CCDS54788.1

UniProtKB/Swiss-Prot

B9A6J1, Q4W5B3, Q4W5E1, Q6NUP4, Q8N7M8, Q8TEA7, Q8WW57, Q96GV6, Q9P080

Related

ENSP00000273980.4, ENST00000273980.10

Conserved Domains (3) summary

smart00164
Location:467 → 671

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:43 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:771 → 882

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...
NM_001163437.3 → NP_001156909.2 TBC domain-containing protein kinase-like protein isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. This results in a shorter protein (isoform b) compared to isoform a.

Source sequence(s)

AC093680, AC107381, AC109361, AC114734

Consensus CDS

CCDS54789.1

Related

ENSP00000378196.3, ENST00000394706.7

Conserved Domains (3) summary

smart00164
Location:428 → 632

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

cd01525
Location:732 → 843

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...

cl21453
Location:43 → 234

PKc_like; Protein Kinases, catalytic domain
NM_001290768.2 → NP_001277697.2 TBC domain-containing protein kinase-like protein isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains an alternate exon compared to variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG resulting in a protein with a shorter N-terminus (isoform d) compared to isoform a.

Source sequence(s)

AC093680, AC107381, AC109361, AC114734

Conserved Domains (3) summary

smart00164
Location:295 → 499

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

cd01525
Location:599 → 710

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...

cl21453
Location:10 → 101

PKc_like; Protein Kinases, catalytic domain
NM_033115.5 → NP_149106.3 TBC domain-containing protein kinase-like protein isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two in-frame exons in the 5' coding region compared to variant 1. This results in a shorter protein (isoform c) compared to isoform a.

Source sequence(s)

AC093680, AC107381, AC109361, AC114734

Consensus CDS

CCDS3673.1

Related

ENSP00000355338.4, ENST00000361687.8

Conserved Domains (3) summary

smart00164
Location:404 → 608

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

cd01525
Location:708 → 819

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...

cl21453
Location:91 → 210

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

106041599..106316683 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047416425.1 → XP_047272381.1 TBC domain-containing protein kinase-like protein isoform X3
XM_017008846.2 → XP_016864335.1 TBC domain-containing protein kinase-like protein isoform X1

UniProtKB/Swiss-Prot

B9A6J1, Q4W5B3, Q4W5E1, Q6NUP4, Q8N7M8, Q8TEA7, Q8WW57, Q96GV6, Q9P080

Conserved Domains (3) summary

smart00164
Location:467 → 671

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:43 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:771 → 882

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...
XM_011532417.3 → XP_011530719.1 TBC domain-containing protein kinase-like protein isoform X1

See identical proteins and their annotated locations for XP_011530719.1

UniProtKB/Swiss-Prot

B9A6J1, Q4W5B3, Q4W5E1, Q6NUP4, Q8N7M8, Q8TEA7, Q8WW57, Q96GV6, Q9P080

Conserved Domains (3) summary

smart00164
Location:467 → 671

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:43 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:771 → 882

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...
XM_024454281.2 → XP_024310049.1 TBC domain-containing protein kinase-like protein isoform X1

UniProtKB/Swiss-Prot

B9A6J1, Q4W5B3, Q4W5E1, Q6NUP4, Q8N7M8, Q8TEA7, Q8WW57, Q96GV6, Q9P080

Conserved Domains (3) summary

smart00164
Location:467 → 671

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:43 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:771 → 882

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...
XM_017008849.2 → XP_016864338.1 TBC domain-containing protein kinase-like protein isoform X6

Conserved Domains (3) summary

smart00164
Location:295 → 499

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

cd01525
Location:599 → 710

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...

cl21453
Location:10 → 101

PKc_like; Protein Kinases, catalytic domain
XM_017008848.2 → XP_016864337.1 TBC domain-containing protein kinase-like protein isoform X4

Conserved Domains (4) summary

smart00164
Location:361 → 565

TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs

smart00220
Location:1 → 167

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd01525
Location:665 → 776

RHOD_Kc; Member of the Rhodanese Homology Domain superfamily. Included in this CD are the rhodanese-like domains found C-terminal of the serine/threonine protein kinases catalytic (S_TKc) domain and the Tre-2, BUB2p, Cdc16p (TBC) domain. The putative active site ...

cl21453
Location:3 → 165

PKc_like; Protein Kinases, catalytic domain
XM_047416426.1 → XP_047272382.1 TBC domain-containing protein kinase-like protein isoform X5
XM_017008847.3 → XP_016864336.1 TBC domain-containing protein kinase-like protein isoform X2
XM_047416423.1 → XP_047272379.1 TBC domain-containing protein kinase-like protein isoform X2
XM_047416424.1 → XP_047272380.1 TBC domain-containing protein kinase-like protein isoform X2
XM_047416422.1 → XP_047272378.1 TBC domain-containing protein kinase-like protein isoform X2
XM_047416427.1 → XP_047272383.1 TBC domain-containing protein kinase-like protein isoform X7

RNA

XR_001741353.3 RNA Sequence
XR_007057984.1 RNA Sequence
XR_007057982.1 RNA Sequence
XR_938800.4 RNA Sequence
XR_007057983.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

109352697..109627755 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054351271.1 → XP_054207246.1 TBC domain-containing protein kinase-like protein isoform X1
XM_054351277.1 → XP_054207252.1 TBC domain-containing protein kinase-like protein isoform X3
XM_054351272.1 → XP_054207247.1 TBC domain-containing protein kinase-like protein isoform X1
XM_054351270.1 → XP_054207245.1 TBC domain-containing protein kinase-like protein isoform X1
XM_054351280.1 → XP_054207255.1 TBC domain-containing protein kinase-like protein isoform X6
XM_054351278.1 → XP_054207253.1 TBC domain-containing protein kinase-like protein isoform X4
XM_054351275.1 → XP_054207250.1 TBC domain-containing protein kinase-like protein isoform X2
XM_054351279.1 → XP_054207254.1 TBC domain-containing protein kinase-like protein isoform X5
XM_054351274.1 → XP_054207249.1 TBC domain-containing protein kinase-like protein isoform X2
XM_054351276.1 → XP_054207251.1 TBC domain-containing protein kinase-like protein isoform X2
XM_054351273.1 → XP_054207248.1 TBC domain-containing protein kinase-like protein isoform X2
XM_054351281.1 → XP_054207256.1 TBC domain-containing protein kinase-like protein isoform X7