TBC1D7

TBC1 domain family member 7, the group of TSC complex

Basic information

Region (hg38): 6:13266542-13328583

Links

ENSG00000145979 ∙ NCBI:51256 ∙ OMIM:612655 ∙ HGNC:21066 ∙ Uniprot:Q9P0N9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrocephaly/megalencephaly syndrome, autosomal recessive (Moderate), mode of inheritance: AR
• macrocephaly/megalencephaly syndrome, autosomal recessive (Limited), mode of inheritance: AR
• macrocephaly/megalencephaly syndrome, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrocephaly/megalencephaly syndrome, autosomal recessive	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; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	23687350; 24515783

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D7 gene.

• not_provided (74 variants)
• not_specified (46 variants)
• TBC1D7-related_disorder (13 variants)
• Macrocephaly/megalencephaly_syndrome,_autosomal_recessive (4 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016495.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18	5	23
missense		1	55	8	1	65
nonsense	1		1			2
start loss						0
frameshift	4	2	1			7
splice donor/acceptor (+/-2bp)		1				1
Total	5	4	57	26	6

Highest pathogenic variant AF is 0.0000545206

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D7	protein_coding	protein_coding	ENST00000606214	7	62042

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.94e-12	0.0217	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.144	168	173	0.969	0.0000102	1924
Missense in Polyphen		39	58.126	0.67095		695
Synonymous	-0.382	67	63.1	1.06	0.00000382	537
Loss of Function	-0.291	17	15.8	1.08	8.17e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000172	0.000109
Finnish	0.000192	0.000185
European (Non-Finnish)	0.000268	0.000264
Middle Eastern	0.000172	0.000109
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question. {ECO:0000269|PubMed:22795129}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Rab regulation of trafficking (Consensus)

Intolerance Scores

• loftool: 0.978
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.486
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d7

Gene ontology

• Biological process: positive regulation of protein ubiquitination;negative regulation of TOR signaling;positive regulation of GTPase activity;response to growth factor;activation of GTPase activity;negative regulation of cilium assembly
• Cellular component: cytosol;cytoplasmic vesicle;ciliary basal body
• Molecular function: GTPase activator activity;protein binding;Rab GTPase binding