TBC1D20

TBC1 domain family member 20

Basic information

Region (hg38): 20:423595-462566

Previous symbols: [ "C20orf140" ]

Links

ENSG00000125875 ∙ NCBI:128637 ∙ OMIM:611663 ∙ HGNC:16133 ∙ Uniprot:Q96BZ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Warburg micro syndrome 4 (Strong), mode of inheritance: AR
• Warburg micro syndrome (Supportive), mode of inheritance: AR
• Warburg micro syndrome 4 (Moderate), mode of inheritance: AR
• Warburg micro syndrome 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warburg micro syndrome 4	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; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	24239381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D20 gene.

• Polyglucosan body myopathy type 1 (106 variants)
• not provided (98 variants)
• Inborn genetic diseases (33 variants)
• not specified (12 variants)
• Warburg micro syndrome 4 (6 variants)
• Polyglucosan body myopathy 1 without immunodeficiency (1 variants)
• Glycogen storage disease, type IV;Polyglucosan body myopathy type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D20 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				19	2	21
missense			41	1	2	44
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2	2		4
non coding	5	4	49	70	27	155
Total	5	5	90	90	31

Highest pathogenic variant AF is 0.0000131

Variants in TBC1D20

This is a list of pathogenic ClinVar variants found in the TBC1D20 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-427295-G-A		Polyglucosan body myopathy type 1	Benign (Dec 27, 2023)
20-427297-C-T		Polyglucosan body myopathy type 1	Likely benign (Dec 06, 2023)
20-427301-G-A		Polyglucosan body myopathy type 1	Likely benign (Sep 10, 2022)
20-427302-T-C		Polyglucosan body myopathy type 1	Likely benign (Jun 20, 2023)
20-427309-G-A		Polyglucosan body myopathy type 1 • RBCK1-related disorder	Likely benign (Nov 25, 2023)
20-427323-C-G		Polyglucosan body myopathy type 1 • Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
20-427327-G-A		Polyglucosan body myopathy type 1	Likely benign (Nov 21, 2021)
20-427332-A-G		Polyglucosan body myopathy type 1	Uncertain significance (Apr 04, 2022)
20-427337-C-T		Polyglucosan body myopathy type 1	Pathogenic (Jul 14, 2023)
20-427338-G-A		Polyglucosan body myopathy type 1	Uncertain significance (Dec 02, 2021)
20-427348-C-T		Polyglucosan body myopathy type 1	Likely benign (Oct 14, 2023)
20-427351-G-C		Polyglucosan body myopathy type 1	Likely benign (Apr 04, 2022)
20-427351-G-T		Polyglucosan body myopathy type 1	Likely benign (Jul 30, 2021)
20-427352-G-A		Polyglucosan body myopathy type 1	Uncertain significance (Dec 07, 2023)
20-427373-C-T		Polyglucosan body myopathy type 1	Uncertain significance (Aug 10, 2022)
20-427374-G-A		Polyglucosan body myopathy type 1	Uncertain significance (Sep 26, 2021)
20-427377-G-T		Polyglucosan body myopathy type 1	Uncertain significance (Jun 09, 2022)
20-427391-C-CT		Polyglucosan body myopathy type 1	Likely pathogenic (-)
20-427392-A-AT		Polyglucosan body myopathy type 1	Pathogenic (Sep 10, 2022)
20-427395-G-T		Glycogen storage disease, type IV;Polyglucosan body myopathy type 1	Pathogenic (Mar 03, 2016)
20-427400-A-T		Polyglucosan body myopathy type 1	Uncertain significance (Nov 28, 2018)
20-427402-C-A		Polyglucosan body myopathy type 1	Likely benign (Jun 29, 2022)
20-427412-AA-CT		Polyglucosan body myopathy type 1	Uncertain significance (Jun 19, 2022)
20-427419-G-A		Polyglucosan body myopathy type 1	Pathogenic (Jul 08, 2023)
20-427432-G-A		Polyglucosan body myopathy type 1	Likely benign (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D20	protein_coding	protein_coding	ENST00000354200	8	27074

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.931	0.0692	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	176	228	0.773	0.0000132	2629
Missense in Polyphen		38	79.357	0.47885		906
Synonymous	0.742	81	90.0	0.900	0.00000488	811
Loss of Function	3.41	2	17.3	0.115	9.00e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude.
• Disease: DISEASE: Warburg micro syndrome 4 (WARBM4) [MIM:615663]: A form of Warburg micro syndrome, a rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. {ECO:0000269|PubMed:24239381}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Rab regulation of trafficking;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.224
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.223
• hipred: Y
• hipred_score: 0.654
• ghis: 0.591

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.359

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d20
• Phenotype: vision/eye phenotype; reproductive system phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: acrosome assembly;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi organization;virion assembly;lipid droplet organization;positive regulation of GTPase activity;positive regulation by host of viral genome replication;positive regulation by virus of viral protein levels in host cell;COPII vesicle coating;lens fiber cell morphogenesis;seminiferous tubule development;COPII-coated vesicle cargo loading;regulation of cilium assembly;positive regulation of ER to Golgi vesicle-mediated transport
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of Golgi membrane;nuclear membrane;endoplasmic reticulum-Golgi intermediate compartment membrane
• Molecular function: GTPase activator activity;protein binding;Rab GTPase binding