TBC1D7 TBC1 domain family member 7 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TBC1D7provided by HGNC
Official Full Name: TBC1 domain family member 7provided by HGNC
Primary source: HGNC:HGNC:21066
See related: Ensembl:ENSG00000145979 MIM:612655; AllianceGenome:HGNC:21066
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: TBC7; MGCPH; PIG51
Summary: This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]
Expression: Ubiquitous expression in heart (RPKM 3.4), testis (RPKM 2.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p24.1

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (13304951..13328537, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (13178191..13201777, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (13305183..13328769, complement)

Chromosome 6 - NC_000006.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

KIF2C: a novel link between Wnt/beta-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma.
Title: KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma.
Discovery of TBC1D7 as a Potential Driver for Melanoma Cell Invasion.
Title: Discovery of TBC1D7 as a Potential Driver for Melanoma Cell Invasion.
findings reveal that Akt activity determines the phosphorylation status of TBC1D7 at the phospho-switch Ser-124, which governs binding to either 14-3-3 or beta-TrCP2, resulting in increased or decreased stability of TBC1D7, respectively.
Title: The tuberous sclerosis complex subunit TBC1D7 is stabilized by Akt phosphorylation-mediated 14-3-3 binding.
Each TBC1D7 molecule interacts simultaneously with two parallel TSC1 helices from two TSC1 molecules, suggesting that TBC1D7 may stabilize the TSC complex by tethering the C-terminal ends of two TSC1 coiled-coils.
Title: Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7).
DNA mutational studies allow enlarging the phenotypic spectrum associated with TBC1D7 mutations and defining a TBC1D7 syndrome.
Title: TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease.
Study suggests that disruption of TBC1D7 causes ID but without the other typical features found in TSC.
Title: Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly.
TBC1D7 knockdown results in increased mTORC1 signaling.
Title: TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1.
Immunohistochemistry of NSCLC tumor tissue suggested an association of TBC1D7 expression with poor prognosis for NSCLC patients; Treatment of lung cancer cells using siRNA against TBC1D7, suppressed its expression and inhibited cell growth.
Title: Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Macrocephaly/megalencephaly syndrome, autosomal recessive MedGen: C3806412 OMIM: 248000 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D6S2113 (e-PCR)
- UniSTS:3631

D1S1423 (e-PCR)
- UniSTS:149619

RH92774 (e-PCR)
- UniSTS:83626

RH46703 (e-PCR)
- UniSTS:41170

Readthrough TBC1D7-LOC100130357

Readthrough gene: TBC1D7-LOC100130357, Included gene: LOC100130357

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables TSC1-TSC2 complex binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in response to growth factor	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of TSC1-TSC2 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of TSC1-TSC2 complex	IDA Inferred from Direct Assay more info	PubMed
part_of TSC1-TSC2 complex	IPI Inferred from Physical Interaction more info	PubMed
located_in ciliary basal body	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: TBC1 domain family member 7

Names: TBC domain family 7; TS complex subunit 3; Tre2-Bub2-Cdc16 Domain Family Member 7; cell migration-inducing protein 23

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_033862.1 RefSeqGene

Range

5047..28633

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001143964.4 → NP_001137436.1 TBC1 domain family member 7 isoform a

See identical proteins and their annotated locations for NP_001137436.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2, 3, and 6 encode the same isoform (a).

Source sequence(s)

AB449888, AK223445, BC050465, DB079098

UniProtKB/Swiss-Prot

E7EV96, Q2TU37, Q53F44, Q5SZL7, Q86VM8, Q96MB8, Q9P0N9

UniProtKB/TrEMBL

Q5SZL4

Related

ENSP00000394425.1, ENST00000422136.5

Conserved Domains (1) summary

cl02495
Location:147 → 251

RabGAP-TBC; Rab-GTPase-TBC domain
NM_001143965.4 → NP_001137437.1 TBC1 domain family member 7 isoform a

See identical proteins and their annotated locations for NP_001137437.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2, 3, and 6 encode the same isoform (a).

Source sequence(s)

BC007054, BC050465, DB079098

UniProtKB/Swiss-Prot

E7EV96, Q2TU37, Q53F44, Q5SZL7, Q86VM8, Q96MB8, Q9P0N9

UniProtKB/TrEMBL

Q5SZL4

Related

ENSP00000348813.4, ENST00000356436.8

Conserved Domains (1) summary

cl02495
Location:147 → 251

RabGAP-TBC; Rab-GTPase-TBC domain
NM_001143966.4 → NP_001137438.1 TBC1 domain family member 7 isoform b

See identical proteins and their annotated locations for NP_001137438.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' UTR and lacks an in-frame exon in the 5' coding region compared to variant 1, which results in a shorter isoform (b) than isoform a.

Source sequence(s)

BC050465, DB079098

Consensus CDS

CCDS47376.1

UniProtKB/TrEMBL

Q5SZL6

Related

ENSP00000368609.2, ENST00000379307.6

Conserved Domains (1) summary

cl02495
Location:120 → 220

RabGAP-TBC; Rab-GTPase-TBC domain
NM_001258457.3 → NP_001245386.1 TBC1 domain family member 7 isoform c

See identical proteins and their annotated locations for NP_001245386.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR and lacks an in-frame exon in the central coding region compared to variant 1, which results in a shorter isoform (c) than isoform a.

Source sequence(s)

AY542308, BC050465, DB079098

Consensus CDS

CCDS58995.1

UniProtKB/TrEMBL

Q5SZL4

Related

ENSP00000343100.4, ENST00000343141.8

Conserved Domains (1) summary

cl02495
Location:129 → 201

RabGAP-TBC; Rab-GTPase-TBC domain
NM_001318805.2 → NP_001305734.1 TBC1 domain family member 7 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2, 3, and 6 encode the same isoform (a).

Source sequence(s)

BC050465, BX354770, DB079098

UniProtKB/Swiss-Prot

E7EV96, Q2TU37, Q53F44, Q5SZL7, Q86VM8, Q96MB8, Q9P0N9

UniProtKB/TrEMBL

Q5SZL4

Conserved Domains (1) summary

cl02495
Location:147 → 251

RabGAP-TBC; Rab-GTPase-TBC domain
NM_001318806.2 → NP_001305735.1 TBC1 domain family member 7 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks multiple 3' coding exons its transcription extends past a splice site used in variant 1, resulting in a different 3' coding region and 3' UTR. The encoded isoform (d) has a shorter, distinct C-terminus compared to isoform a.

Source sequence(s)

AL589984, AL833474

Consensus CDS

CCDS83062.1

UniProtKB/TrEMBL

U3KPY5

Related

ENSP00000475355.1, ENST00000606370.5
NM_016495.6 → NP_057579.1 TBC1 domain family member 7 isoform a

See identical proteins and their annotated locations for NP_057579.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1, 2, 3, and 6 encode the same isoform (a).

Source sequence(s)

AF151073, BC050465, DB079098

UniProtKB/Swiss-Prot

E7EV96, Q2TU37, Q53F44, Q5SZL7, Q86VM8, Q96MB8, Q9P0N9

UniProtKB/TrEMBL

Q5SZL4

Related

ENSP00000368602.3, ENST00000379300.8

Conserved Domains (1) summary

cl02495
Location:147 → 251

RabGAP-TBC; Rab-GTPase-TBC domain