TANGO2

transport and golgi organization 2 homolog, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 22:20017013-20067164

Previous symbols: [ "C22orf25" ]

Links

ENSG00000183597 ∙ NCBI:128989 ∙ OMIM:616830 ∙ HGNC:25439 ∙ Uniprot:Q6ICL3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (Strong), mode of inheritance: AR
• metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration	AR	Biochemical; Cardiovascular; Musculoskeletal	Individuals may have cardiac arrhythmias and acute episodes of rhabdomyolysis, as well as hypoglycemia and lactic acidemia, and awareness may allow prompt management	Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic	26805781; 26805782

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TANGO2 gene.

• not provided (304 variants)
• Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (25 variants)
• Inborn genetic diseases (15 variants)
• not specified (2 variants)
• Cardiac arrhythmia;Seizure;Episodic flaccid weakness;Acute rhabdomyolysis;Intellectual disability (2 variants)
• See cases (2 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• TANGO2-related condition (1 variants)
• Cardiac arrhythmia;Seizure;Acute rhabdomyolysis;Episodic flaccid weakness;Intellectual disability (1 variants)
• Metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TANGO2 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				62	2	64
missense		2	110	4	1	117
nonsense	5	2				7
start loss			1			1
frameshift	5	1				6
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	7				9
splice region		1	8	8		17
non coding			1	68	26	95
Total	12	12	114	134	29

Highest pathogenic variant AF is 0.0000547

Variants in TANGO2

This is a list of pathogenic ClinVar variants found in the TANGO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-20036651-A-G			Benign (Jun 19, 2018)
22-20036795-C-A		TANGO2-related disorder	Likely benign (Nov 25, 2020)
22-20036799-A-G			Uncertain significance (Aug 23, 2022)
22-20036801-GT-G		Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome	Pathogenic (Nov 06, 2023)
22-20036804-C-T			Likely benign (Mar 12, 2022)
22-20036808-A-C			Uncertain significance (Aug 10, 2023)
22-20036808-ATCT-A		Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome	Uncertain significance (May 21, 2021)
22-20036809-T-A			Uncertain significance (Oct 19, 2022)
22-20036813-CTTT-C			Uncertain significance (Sep 29, 2023)
22-20036816-T-C			Likely benign (May 14, 2023)
22-20036829-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
22-20036830-G-A			Uncertain significance (Aug 16, 2022)
22-20036832-CCT-C			Pathogenic (Dec 08, 2022)
22-20036834-T-A			Likely benign (Oct 09, 2022)
22-20036835-G-C			Uncertain significance (Sep 19, 2022)
22-20036843-A-G			Likely benign (Nov 27, 2023)
22-20036846-C-T			Likely benign (Jan 21, 2024)
22-20036847-G-A			Uncertain significance (Jan 22, 2024)
22-20036848-C-T			Uncertain significance (Jul 31, 2021)
22-20036849-G-A			Likely benign (Dec 19, 2023)
22-20036850-T-A			Uncertain significance (Oct 24, 2022)
22-20036858-A-G			Uncertain significance (Aug 09, 2022)
22-20036859-C-A			Uncertain significance (Jul 04, 2022)
22-20036860-C-T			Uncertain significance (Jul 06, 2022)
22-20036861-C-G			Likely benign (Oct 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TANGO2	protein_coding	protein_coding	ENST00000327374	8	48913

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000148	0.968	125723	0	22	125745	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.448	152	168	0.903	0.0000103	1789
Missense in Polyphen		60	65.752	0.91252		767
Synonymous	1.18	59	71.7	0.823	0.00000505	523
Loss of Function	1.92	9	17.7	0.507	0.00000117	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000887	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.000295	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) [MIM:616878]: An autosomal recessive disorder characterized by metabolic encephalomyopathic crises, hypoglycemia, hyperammonemia, episodic rhabdomyolysis, susceptibility to life-threatening cardiac tachyarrhythmias, developmental delay, mental retardation, and mild diffuse cerebral atrophy. {ECO:0000269|PubMed:26805781, ECO:0000269|PubMed:26805782}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0980

Intolerance Scores

• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.0809
• hipred: N
• hipred_score: 0.238
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tango2

Gene ontology

• Biological process: Golgi organization;protein secretion
• Cellular component: Golgi apparatus