TBC1D7

Summary

TBC1D7 (TBC1 domain family member 7, HGNC:21066) is a protein-coding gene on chromosome 6p24.1, encoding TBC1 domain family member 7 (Q9P0N9). Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular bio….

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.

Source: NCBI Gene 51256 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macrocephaly/megalencephaly syndrome, autosomal recessive (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 131 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 38
• MANE Select transcript: NM_016495

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21066
Approved symbol	TBC1D7
Name	TBC1 domain family member 7
Location	6p24.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ257A7.3, FLJ32666, TBC7
Ensembl gene	ENSG00000145979
Ensembl biotype	protein_coding
OMIM	612655
Entrez	51256

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 49 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000343141, ENST00000356436, ENST00000379291, ENST00000379300, ENST00000379307, ENST00000416436, ENST00000420456, ENST00000421203, ENST00000422136, ENST00000428109, ENST00000446018, ENST00000450347, ENST00000452989, ENST00000606214, ENST00000606370, ENST00000606530, ENST00000606541, ENST00000607208, ENST00000607230, ENST00000607532, ENST00000607658, ENST00000906917, ENST00000906918, ENST00000906919, ENST00000906920, ENST00000906921, ENST00000906922, ENST00000906923, ENST00000906924, ENST00000906925, ENST00000906926, ENST00000906927, ENST00000906928, ENST00000906929, ENST00000906930, ENST00000906931, ENST00000906932, ENST00000921250, ENST00000921251, ENST00000921252, ENST00000921253, ENST00000921254, ENST00000921255, ENST00000921256, ENST00000921257, ENST00000921258, ENST00000921259, ENST00000921260, ENST00000952330, ENST00000952331, ENST00000952332, ENST00000952333

RefSeq mRNA: 8 — MANE Select: NM_016495 NM_001143964, NM_001143965, NM_001143966, NM_001258457, NM_001318805, NM_001318806, NM_001318809, NM_016495

CCDS: CCDS47376, CCDS58995, CCDS83062

Canonical transcript exons

ENST00000379300 — 8 exons

Exon	Start	End
ENSE00001156039	13316571	13316708
ENSE00001156050	13320908	13321095
ENSE00001906838	13304951	13305187
ENSE00001966425	13325094	13325174
ENSE00002713772	13326787	13326906
ENSE00003786356	13306398	13306527
ENSE00003791323	13307600	13307745
ENSE00003842458	13328296	13328537

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 92.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.4854 / max 422.4673, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71826	18.9536	1810
71824	0.2696	90
71825	0.2622	137

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.27	gold quality
oocyte	CL:0000023	91.69	gold quality
ganglionic eminence	UBERON:0004023	90.64	gold quality
apex of heart	UBERON:0002098	90.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.06	gold quality
right atrium auricular region	UBERON:0006631	89.62	gold quality
heart left ventricle	UBERON:0002084	89.11	gold quality
mucosa of transverse colon	UBERON:0004991	89.05	gold quality
cardiac atrium	UBERON:0002081	88.73	gold quality
cardiac ventricle	UBERON:0002082	88.59	gold quality
secondary oocyte	CL:0000655	88.56	gold quality
ventricular zone	UBERON:0003053	88.14	gold quality
stromal cell of endometrium	CL:0002255	87.86	gold quality
bone marrow cell	CL:0002092	87.84	gold quality
prefrontal cortex	UBERON:0000451	87.60	gold quality
metanephros cortex	UBERON:0010533	87.56	gold quality
heart	UBERON:0000948	87.50	gold quality
middle temporal gyrus	UBERON:0002771	87.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.92	gold quality
islet of Langerhans	UBERON:0000006	86.52	gold quality
rectum	UBERON:0001052	86.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.11	gold quality
anterior cingulate cortex	UBERON:0009835	85.59	gold quality
right frontal lobe	UBERON:0002810	85.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.13	gold quality
esophagus mucosa	UBERON:0002469	85.11	gold quality
granulocyte	CL:0000094	85.03	gold quality
gastrocnemius	UBERON:0001388	84.83	gold quality
left ventricle myocardium	UBERON:0006566	84.57	gold quality
muscle of leg	UBERON:0001383	84.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting TBC1D7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4665-5P	97.91	67.69	1536

Literature-anchored findings (GeneRIF, showing 8)

• 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. (PMID:20095038)
• TBC1D7 knockdown results in increased mTORC1 signaling. (PMID:22795129)
• Study suggests that disruption of TBC1D7 causes ID but without the other typical features found in TSC. (PMID:23687350)
• DNA mutational studies allow enlarging the phenotypic spectrum associated with TBC1D7 mutations and defining a TBC1D7 syndrome. (PMID:24515783)
• 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. (PMID:26893383)
• 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. (PMID:30143532)
• Discovery of TBC1D7 as a Potential Driver for Melanoma Cell Invasion. (PMID:32510182)
• KIF2C: a novel link between Wnt/beta-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma. (PMID:32748349)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d7	ENSDARG00000029581
mus_musculus	Tbc1d7	ENSMUSG00000021368
rattus_norvegicus	Tbc1d7	ENSRNOG00000014019
drosophila_melanogaster	TBC1d7	FBGN0039158

Protein

Protein identifiers

TBC1 domain family member 7 — Q9P0N9 (reviewed: Q9P0N9)

Alternative names: Cell migration-inducing protein 23

All UniProt accessions (14): B4DK47, Q9P0N9, Q5SZL3, Q5SZL4, Q5SZL5, Q5SZL6, Q5SZL8, Q5SZM1, Q5SZM2, U3KPS8, U3KPY5, U3KQ23, U3KQD8, U3KQQ0

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling. The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1.

Subunit / interactions. Component of the TSC-TBC complex (also named Rhebulator complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1 molecule of TBC1D7. Interacts with TSC1 (via C-terminal half of the coiled-coil domain).

Subcellular location. Lysosome membrane. Cytoplasmic vesicle. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in heart, and slightly in kidney, liver and placenta.

Disease relevance. Macrocephaly/megalencephaly syndrome, autosomal recessive (MGCPH) [MIM:248000] An autosomal recessive disorder characterized by abnormal enlargement of the cerebral hemispheres, intellectual disability, large head, optic atrophy and underdeveloped skeletal musculature. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Additional clinical features include behavioral abnormalities, psychosis, learning difficulties, prognathism, myopia and astigmatism. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9P0N9-1	1	yes
Q9P0N9-2	2
Q9P0N9-3	3
Q9P0N9-4	4

RefSeq proteins (8): NP_001137436, NP_001137437, NP_001137438, NP_001245386, NP_001305734, NP_001305735, NP_001305738, NP_057579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR039842	TBC1D7	Family
IPR043039	TBC1D7_dom2	Homologous_superfamily

Pfam: PF00566

UniProt features (36 total): helix 18, mutagenesis site 5, strand 3, splice variant 3, turn 2, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3QWL	X-RAY DIFFRACTION	1.9
5ULO	X-RAY DIFFRACTION	2.14
4Z6Y	X-RAY DIFFRACTION	2.81
9CE3	ELECTRON MICROSCOPY	2.9
5EJC	X-RAY DIFFRACTION	3.1
7DL2	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0N9-F1	92.65	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (5):

Position	Phenotype
114	abolished interaction with tsc1.
121	abolished formation of the tsc-tbc complex; when associated with 81-a–a-84.
81–84	abolished formation of the tsc-tbc complex; when associated with a-121. abolished interaction with tsc1 and tsc2; when a
94–95	abolished interaction with tsc1. abolished interaction with tsc1 and tsc2; when associated with a-81–a-84.
96	decreased interaction with tsc1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 258 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOCC_VACUOLAR_MEMBRANE, chr6p24, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_GTPASE_ACTIVITY, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (8): cellular response to starvation (GO:0009267), positive regulation of protein ubiquitination (GO:0031398), negative regulation of TOR signaling (GO:0032007), positive regulation of GTPase activity (GO:0043547), response to growth factor (GO:0070848), activation of GTPase activity (GO:0090630), negative regulation of cilium assembly (GO:1902018), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (4): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), TSC1-TSC2 complex binding (GO:0062078), protein binding (GO:0005515)

GO Cellular Component (9): lysosomal membrane (GO:0005765), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), TSC1-TSC2 complex (GO:0033596), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), lysosome (GO:0005764), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
GTPase activity	2
cytoplasm	2
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
TOR signaling	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
response to endogenous stimulus	1
positive regulation of GTPase activity	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
protein-containing complex binding	1
binding	1
lysosome	1
lytic vacuole membrane	1
intracellular vesicle	1
cytosol	1
protein-containing complex	1
microtubule organizing center	1
cilium	1
intracellular anatomical structure	1
lytic vacuole	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D7	TSC2	P49815	998
TBC1D7	TSC1	Q92574	997
TBC1D7	USP6	P35125	956
TBC1D7	CDC16	Q13042	896
TBC1D7	RHEB	Q15382	819
TBC1D7	RPS6KB1	P23443	744
TBC1D7	RPS6	P08227	701
TBC1D7	NPRL3	Q12980	681
TBC1D7	NPRL2	Q8WTW4	679
TBC1D7	PHLPP1	O60346	676
TBC1D7	AKT1	P31749	666
TBC1D7	RASA1	P20936	659
TBC1D7	RRAGB	Q5VZM2	653
TBC1D7	RRAGC	Q9HB90	653
TBC1D7	RRAGA	Q7L523	651

IntAct

106 interactions, top by confidence:

A	B	Type	Score
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
TRAF4	TBC1D7	psi-mi:“MI:0915”(physical association)	0.840
TBC1D7	TRAF4	psi-mi:“MI:0915”(physical association)	0.840
TBC1D7	SSNA1	psi-mi:“MI:0915”(physical association)	0.780
TBC1D7	KRT19	psi-mi:“MI:0915”(physical association)	0.780
TBC1D7	HOOK1	psi-mi:“MI:0915”(physical association)	0.780
KRT19	TBC1D7	psi-mi:“MI:0915”(physical association)	0.780
HOOK1	TBC1D7	psi-mi:“MI:0915”(physical association)	0.780
SSNA1	TBC1D7	psi-mi:“MI:0915”(physical association)	0.780
BECN1	ZWINT	psi-mi:“MI:0914”(association)	0.750
LDOC1	TBC1D7	psi-mi:“MI:0915”(physical association)	0.720
TBC1D7	BLZF1	psi-mi:“MI:0915”(physical association)	0.720
TBC1D7	LDOC1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (108): TBC1D7 (Two-hybrid), TBC1D7 (Two-hybrid), TBC1D7 (Two-hybrid), TBC1D7 (Two-hybrid), TBC1D7 (Two-hybrid), HOOK1 (Two-hybrid), RPGRIP1 (Two-hybrid), LZTS2 (Two-hybrid), TBC1D7 (Affinity Capture-RNA), TSC1 (Affinity Capture-MS), TSC2 (Affinity Capture-MS), KIF27 (Affinity Capture-MS), TBC1D7 (Affinity Capture-MS), TBC1D7 (Affinity Capture-MS), TBC1D7 (Affinity Capture-MS)

ESM2 similar proteins: A1A5K6, A6H8I2, F1M386, F1PBJ0, F1QRX7, F1QWA8, F6UMY3, O02697, O14830, O97790, P26675, P48736, Q08CX5, Q21029, Q29RJ2, Q2KI13, Q3UUG6, Q3UYK3, Q3V3E1, Q5E9C4, Q5R8B7, Q5SVR0, Q5ZJX5, Q66K14, Q6DDI6, Q6DDZ9, Q6DEY8, Q6P6R7, Q6ZT07, Q7T2D0, Q8BGG7, Q8CHG7, Q8R5A6, Q8TC07, Q8TEU7, Q8TF42, Q8VCZ6, Q8WZA2, Q91WS7, Q95LL3

Diamond homologs: F1QRX7, F6UMY3, Q5E9C4, Q9D0K0, Q9P0N9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AKT	“up-regulates quantity by stabilization”	TBC1D7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	141.0×	2e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	124.4×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	124.4×	2e-08
Activation of BH3-only proteins	5	92.0×	6e-08
RHO GTPases activate PKNs	5	58.7×	6e-07
Intrinsic Pathway for Apoptosis	5	54.2×	7e-07
TP53 Regulates Metabolic Genes	7	33.6×	5e-08
Transcriptional and post-translational regulation of MITF-M expression and activity	5	33.0×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of TORC1 signaling	5	45.0×	3e-05
intracellular protein localization	6	17.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

131 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	56
Likely benign	31
Benign	23

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
144034	NM_016495.6(TBC1D7):c.18_21del (p.Arg7fs)	Pathogenic
2062902	NM_016495.6(TBC1D7):c.322dup (p.Tyr108fs)	Pathogenic
2705589	NM_016495.6(TBC1D7):c.672G>A (p.Trp224Ter)	Pathogenic
3691720	NM_016495.6(TBC1D7):c.375del (p.Pro126fs)	Pathogenic
2758290	NM_016495.6(TBC1D7):c.194-64_233delinsC	Likely pathogenic
809878	NM_016495.6(TBC1D7):c.788del (p.Leu263fs)	Likely pathogenic

SpliceAI

2208 predictions. Top by Δscore:

Variant	Effect	Δscore
6:13278266:A:AG	acceptor_gain	1.0000
6:13278267:G:GG	acceptor_gain	1.0000
6:13283417:TGCA:T	acceptor_loss	1.0000
6:13283417:TGCAG:T	acceptor_gain	1.0000
6:13283418:GCA:G	acceptor_loss	1.0000
6:13283419:CA:C	acceptor_loss	1.0000
6:13283420:A:AG	acceptor_gain	1.0000
6:13283420:AGCTC:A	acceptor_loss	1.0000
6:13283421:G:GA	acceptor_gain	1.0000
6:13283421:GC:G	acceptor_gain	1.0000
6:13283421:GCT:G	acceptor_gain	1.0000
6:13283421:GCTC:G	acceptor_gain	1.0000
6:13283421:GCTCA:G	acceptor_gain	1.0000
6:13283528:A:G	donor_gain	1.0000
6:13283558:ACAAA:A	donor_gain	1.0000
6:13283559:CAAA:C	donor_gain	1.0000
6:13283559:CAAAG:C	donor_loss	1.0000
6:13283560:AAA:A	donor_gain	1.0000
6:13283560:AAAG:A	donor_loss	1.0000
6:13283561:AA:A	donor_gain	1.0000
6:13283562:AGTAA:A	donor_loss	1.0000
6:13283563:G:GG	donor_gain	1.0000
6:13283563:GTA:G	donor_loss	1.0000
6:13283564:T:G	donor_loss	1.0000
6:13283574:G:T	donor_gain	1.0000
6:13286144:A:AG	acceptor_gain	1.0000
6:13286145:G:GG	acceptor_gain	1.0000
6:13306391:CACT:C	donor_loss	1.0000
6:13306392:ACTT:A	donor_loss	1.0000
6:13306393:CT:C	donor_loss	1.0000

AlphaMissense

1931 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:13325109:A:G	W60R	1.000
6:13325109:A:T	W60R	1.000
6:13325140:G:C	F49L	1.000
6:13325140:G:T	F49L	1.000
6:13325142:A:G	F49L	1.000
6:13326846:C:T	G18E	1.000
6:13326872:A:C	F9L	1.000
6:13326872:A:T	F9L	1.000
6:13326874:A:G	F9L	1.000
6:13305151:C:G	A278P	0.999
6:13306519:T:A	D225V	0.999
6:13306519:T:G	D225A	0.999
6:13306520:C:G	D225H	0.999
6:13306523:A:G	W224R	0.999
6:13306523:A:T	W224R	0.999
6:13307649:A:G	W206R	0.999
6:13307649:A:T	W206R	0.999
6:13325152:A:C	F45L	0.999
6:13325152:A:T	F45L	0.999
6:13325154:A:G	F45L	0.999
6:13326807:A:G	L31P	0.999
6:13326847:C:A	G18W	0.999
6:13326847:C:G	G18R	0.999
6:13326847:C:T	G18R	0.999
6:13326862:A:C	Y13D	0.999
6:13326862:A:G	Y13H	0.999
6:13326871:G:C	R10G	0.999
6:13326871:G:T	R10S	0.999
6:13326873:A:C	F9C	0.999
6:13326873:A:G	F9S	0.999

dbSNP variants (sampled 300 via entrez): RS1000203086 (6:13315721 A>G,T), RS1000407461 (6:13322364 T>C), RS1000561460 (6:13328516 C>T), RS1000581050 (6:13328111 G>C), RS1000597184 (6:13314645 T>A), RS1000694125 (6:13308232 G>C), RS1000933428 (6:13328430 C>G), RS1001353499 (6:13326039 G>C), RS1001424802 (6:13305254 G>A), RS1001438666 (6:13306014 G>A), RS1001550826 (6:13310294 G>A), RS1001607747 (6:13311664 T>A,C), RS1001730991 (6:13316981 G>C), RS1001760650 (6:13316777 A>C), RS1001909090 (6:13323158 G>C)

Disease associations

OMIM: gene MIM:612655 | disease phenotypes: MIM:248000

GenCC curated gene-disease

Disease	Classification	Inheritance
macrocephaly/megalencephaly syndrome, autosomal recessive	Strong	Autosomal recessive

Mondo (1): macrocephaly/megalencephaly syndrome, autosomal recessive (MONDO:0009544)

Orphanet (0):

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000040	Long penis
HP:0000053	Macroorchidism
HP:0000235	Abnormal cranial suture/fontanelle morphology
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000280	Coarse facial features
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000545	Myopia
HP:0000648	Optic atrophy
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001355	Megalencephaly
HP:0001631	Atrial septal defect
HP:0001956	Truncal obesity
HP:0002007	Frontal bossing
HP:0002608	Celiac disease

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002078_30	Migraine without aura	3.000000e-10
GCST002081_27	Migraine	5.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537453	Mental retardation, macrocephaly, short stature and craniofacial dysmorphism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance, increases expression	4
Acetaminophen	increases expression	2
Benzene	increases expression	2
Cyclosporine	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	increases expression	1
Resveratrol	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects splicing	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Tunicamycin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2I7	Abcam HeLa TBC1D7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.