TANGO2

protein-coding

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

Gene summary

This gene belongs to the transport and Golgi organization family, whose members are predicted to play roles in secretory protein loading in the endoplasmic reticulum. Depletion of this gene in Drosophila S2 cells causes fusion of the Golgi with the ER. In mouse tissue culture cells, this protein co-localizes with a mitochondrially targeted mCherry protein and displays very low levels of co-localization with Golgi and peroxisomes. Allelic variants of this gene are associated with rhabdomyolysis, metabolic crises with encephalopathy, and cardiac arrhythmia. [provided by RefSeq, Apr 2016]

Previous symbols:

C22orf25

MANE transcript

NM_152906.7

Inheritance

ClinVar variants

P:45U:134B:126

Top phenotype

Metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr22:20,017,014-20,067,164

External References & Databases

Ensembl (ENSG00000183597)

Transcript & Mutation Effects

hg38 • Region Span ~50.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018820

Submitter: G2P

recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018820

Submitter: PanelApp Australia

recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018820

Submitter: Labcorp Genetics (formerly Invitae)

metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegenerationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014812

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegenerationAR

Manifestation: Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic

Intervention: Biochemical; Cardiovascular; Musculoskeletal

Rationale: Individuals may have cardiac arrhythmias and acute episodes of rhabdomyolysis, as well as hypoglycemia and lactic acidemia, and awareness may allow prompt management

Refs: 26805781; 26805782

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TANGO2 variants in ClinVar

14 Conditions Cataloged

not providedTotal: 414

Inborn genetic diseasesTotal: 49

not specifiedTotal: 41

Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndromeTotal: 34

TANGO2-related disorderTotal: 31

Acute rhabdomyolysisTotal: 5

Episodic flaccid weaknessTotal: 3

Intellectual disabilityTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152906.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	115 clinvar	1 clinvar	117
missense		7 clinvar	129 clinvar	9 clinvar	1 clinvar	146
nonsense	12 clinvar	4 clinvar	1 clinvar			17
start loss			1 clinvar			1
frameshift	6 clinvar	2 clinvar	1 clinvar			9
splice donor/acceptor (+/-2bp)	2 clinvar	12 clinvar	1 clinvar			15
Total	20	25	134	124	2	305

Highest pathogenic variant AF is 0.0000355107

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 140 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152906.7	RefSeq	NP_690870.3	8	MANE Select
ENST00000327374.9	Ensembl	ENSP00000332721.4	8	MANE Select
NM_001283106.3	RefSeq	NP_001270035.1	8	Standard
NM_001283116.3	RefSeq	NP_001270045.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

Golgi organization
protein secretion

Cellular Component

Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327374
Coding exons: 8
Length: 48913
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125745
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.448	152	168	0.903	0.0000103	1789
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00029	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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