TANGO2

Chr 22AR

transport and golgi organization 2 homolog

Also known as: C22orf25, MECRCN

NCBI Gene: 128989ENSG00000183597UniProt: Q6ICL3

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]

Primary Disease Associations & Inheritance

Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegenerationMIM #616878
AR
UniProtMetabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
795
ClinVar variants
361
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— TANGO2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
361 Pathogenic / Likely Pathogenic· 164 VUS of 795 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 1.92
OE 0.51 (0.30–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.90 (0.79–1.03)
152 obs / 168.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.30–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.79–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.82
0≤1.21.6
LoF obs/exp: 9 / 17.7Missense obs/exp: 152 / 168.4Syn Z: 1.18

ClinVar Variant Classifications

795 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic334
Likely Pathogenic27
VUS164
Likely Benign243
Benign21
Conflicting6
334
Pathogenic
27
Likely Pathogenic
164
VUS
243
Likely Benign
21
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
5
322
0
334
Likely Pathogenic
13
6
8
0
27
VUS
3
128
33
0
164
Likely Benign
2
40
110
91
243
Benign
0
4
17
0
21
Conflicting
—6
Total2518349091795

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TANGO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TANGO2-related infancy-onset recurrent metabolic crises with encephalocardiomyopathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

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

MIM #616878

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TANGO2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variable clinical severity in TANGO2 deficiency: Case series and literature review.
Schymick J et al.·Am J Med Genet A
2022Review
TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.
Dines JN et al.·Genet Med
2019
Mitochondrial dysfunction associated with TANGO2 deficiency.
Heiman P et al.·Sci Rep
2022
Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder.
Xu W et al.·JCI Insight
2024
Clinical phenotype associated with variants in TANGO2: A case study.
Alghamdi F et al.·Arch Pediatr
2023Case report
Recent advances in our understanding of genetic rhabdomyolysis.
Cabrera-Serrano M et al.·Curr Opin Neurol
2022Review
Clinical presentation and proteomic signature of patients with TANGO2 mutations.
Mingirulli N et al.·J Inherit Metab Dis
2020Case report
Clinical phenotype associated with TANGO2 gene mutation.
Hoebeke C et al.·Arch Pediatr
2021Case report
Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.
Bérat CM et al.·J Inherit Metab Dis
2021Cohort
The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an αββα-Fold Arrangement.
Cooper A et al.·Proteins
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools