TANGO2

Summary

TANGO2 (transport and golgi organization 2 homolog, HGNC:25439) is a protein-coding gene on chromosome 22q11.21, encoding Transport and Golgi organization protein 2 homolog (Q6ICL3). May be involved in lipid homeostasis.

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.

Source: NCBI Gene 128989 — RefSeq curated summary.

At a glance

• Gene–disease (curated): recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 508 total — 47 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 92
• MANE Select transcript: NM_152906

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25439
Approved symbol	TANGO2
Name	transport and golgi organization 2 homolog
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761P1121
Ensembl gene	ENSG00000183597
Ensembl biotype	protein_coding
OMIM	616830
Entrez	128989

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 26 protein_coding, 7 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000327374, ENST00000398042, ENST00000399807, ENST00000401833, ENST00000401886, ENST00000411907, ENST00000420290, ENST00000430807, ENST00000432198, ENST00000432883, ENST00000434168, ENST00000434570, ENST00000444651, ENST00000447208, ENST00000450019, ENST00000450664, ENST00000456048, ENST00000462579, ENST00000471707, ENST00000475446, ENST00000476940, ENST00000479679, ENST00000484373, ENST00000485715, ENST00000490121, ENST00000490583, ENST00000852305, ENST00000852306, ENST00000852307, ENST00000852308, ENST00000852309, ENST00000852310, ENST00000852311, ENST00000938895, ENST00000938896, ENST00000957774, ENST00000957775, ENST00000957776, ENST00000957777, ENST00000957778

RefSeq mRNA: 34 — MANE Select: NM_152906 NM_001283106, NM_001283116, NM_001283129, NM_001283148, NM_001283154, NM_001283179, NM_001283186, NM_001283199, NM_001283215, NM_001283235, NM_001283248, NM_001322141, NM_001322142, NM_001322143, NM_001322144, NM_001322145, NM_001322146, NM_001322147, NM_001322148, NM_001322149, NM_001322150, NM_001322153, NM_001322155, NM_001322160, NM_001322163, NM_001322166, NM_001322167, NM_001322169, NM_001322171, NM_001322172, NM_001322173, NM_001322174, NM_001322175, NM_152906

CCDS: CCDS13772, CCDS63404, CCDS63405, CCDS63406, CCDS63407, CCDS74821, CCDS74822

Canonical transcript exons

ENST00000327374 — 9 exons

Exon	Start	End
ENSE00001325554	20021110	20021246
ENSE00003487203	20043355	20043443
ENSE00003502217	20061530	20061683
ENSE00003513418	20055943	20056013
ENSE00003576153	20036760	20036854
ENSE00003594113	20053437	20053551
ENSE00003752706	20063338	20063442
ENSE00003790374	20052465	20052584
ENSE00003893650	20064542	20067164

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1991 / max 218.7305, expressed in 1793 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191099	9.6341	1789
191100	0.8784	490
191101	0.3856	206
191098	0.3010	153

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.59	gold quality
granulocyte	CL:0000094	96.43	gold quality
blood	UBERON:0000178	95.77	gold quality
monocyte	CL:0000576	95.71	gold quality
right atrium auricular region	UBERON:0006631	95.65	gold quality
left ventricle myocardium	UBERON:0006566	95.58	silver quality
leukocyte	CL:0000738	95.46	gold quality
cardiac atrium	UBERON:0002081	95.29	gold quality
heart left ventricle	UBERON:0002084	95.26	gold quality
right lobe of thyroid gland	UBERON:0001119	94.92	gold quality
cardiac ventricle	UBERON:0002082	94.83	gold quality
right coronary artery	UBERON:0001625	94.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.59	gold quality
metanephros cortex	UBERON:0010533	94.57	gold quality
left lobe of thyroid gland	UBERON:0001120	94.42	gold quality
spleen	UBERON:0002106	94.38	gold quality
heart	UBERON:0000948	93.95	gold quality
descending thoracic aorta	UBERON:0002345	93.75	gold quality
thyroid gland	UBERON:0002046	93.68	gold quality
body of stomach	UBERON:0001161	93.56	gold quality
popliteal artery	UBERON:0002250	93.44	gold quality
tibial artery	UBERON:0007610	93.44	gold quality
thoracic aorta	UBERON:0001515	93.41	gold quality
ascending aorta	UBERON:0001496	93.40	gold quality
aorta	UBERON:0000947	93.35	gold quality
right adrenal gland	UBERON:0001233	93.12	gold quality
right adrenal gland cortex	UBERON:0035827	93.06	gold quality
left adrenal gland cortex	UBERON:0035825	93.02	gold quality
left adrenal gland	UBERON:0001234	92.99	gold quality
left coronary artery	UBERON:0001626	92.84	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	27.42
E-MTAB-9388	yes	7.76
E-MTAB-7303	no	252.01
E-GEOD-100618	no	233.54
E-MTAB-7249	no	72.09
E-HCAD-10	no	2.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting TANGO2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-122B-3P	99.21	68.90	1333

Literature-anchored findings (GeneRIF, showing 11)

• Exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations. (PMID:26805781)
• Variants from the 14 patients described are shown above the gene depiction with red bars for deletions and lines for single nucleotide variants (SNV), and pathogenic variants from prior studies are shown below (light blue bars for deletions and lines for SNV) based on TANGO2 transcript NM152906.6 (2623 bp). (PMID:30245509)
• TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism. (PMID:31276219)
• Clinical presentation and proteomic signature of patients with TANGO2 mutations. (PMID:31339582)
• The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria. (PMID:32909282)
• Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect. (PMID:32929747)
• Clinical phenotype associated with TANGO2 gene mutation. (PMID:33342685)
• Variable clinical severity in TANGO2 deficiency: Case series and literature review. (PMID:34668327)
• Mitochondrial dysfunction associated with TANGO2 deficiency. (PMID:35197517)
• Molecular insight into CREBBP and TANGO2 variants causing intellectual disability. (PMID:37721116)
• Lipidomic analysis of human TANGO2-deficient cells suggests a lipid imbalance as a cause of TANGO2 deficiency disease. (PMID:38718569)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tango2	ENSDARG00000056550
mus_musculus	Tango2	ENSMUSG00000013539
rattus_norvegicus	Tango2	ENSRNOG00000030245
drosophila_melanogaster	Tango2	FBGN0030503
caenorhabditis_elegans		WBGENE00011305
caenorhabditis_elegans		WBGENE00013587

Protein

Protein identifiers

Transport and Golgi organization protein 2 homolog — Q6ICL3 (reviewed: Q6ICL3)

All UniProt accessions (9): Q6ICL3, A0A0A0MSI5, A8MWT1, B7Z4A5, C9J695, C9JDT9, C9JKN2, F6S117, F8WDT9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in lipid homeostasis.

Subcellular location. Cytoplasm. Mitochondrion. Golgi apparatus.

Disease relevance. Metabolic 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, intellectual disability, and mild diffuse cerebral atrophy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Tango2 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q6ICL3-1	1	yes
Q6ICL3-2	2
Q6ICL3-3	3
Q6ICL3-4	4
Q6ICL3-5	5
Q6ICL3-6	6

RefSeq proteins (34): NP_001270035, NP_001270045, NP_001270058, NP_001270077, NP_001270083, NP_001270108, NP_001270115, NP_001270128, NP_001270144, NP_001270164, NP_001270177, NP_001309070, NP_001309071, NP_001309072, NP_001309073, NP_001309074, NP_001309075, NP_001309076, NP_001309077, NP_001309078, NP_001309079, NP_001309082, NP_001309084, NP_001309089, NP_001309092, NP_001309095, NP_001309096, NP_001309098, NP_001309100, NP_001309101, NP_001309102, NP_001309103, NP_001309104, NP_690870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008551	TANGO2	Family

Pfam: PF05742

UniProt features (27 total): sequence variant 18, splice variant 7, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8SV7	X-RAY DIFFRACTION	1.53
9BWA	X-RAY DIFFRACTION	1.7
9N1S	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ICL3-F1	95.43	0.90

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 (1):

Position	Phenotype
1–40	abolishes mitochondrial localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 246 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, TGCTGAY_UNKNOWN, GOBP_SECRETION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GOLGI_ORGANIZATION, STARK_HYPPOCAMPUS_22Q11_DELETION_DN, YOSHIMURA_MAPK8_TARGETS_UP, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN, PILON_KLF1_TARGETS_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, LIM_MAMMARY_STEM_CELL_DN

GO Biological Process (2): Golgi organization (GO:0007030), protein secretion (GO:0009306)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
organelle organization	1
endomembrane system organization	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
binding	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TANGO2	MRPL40	Q9NQ50	761
TANGO2	ZDHHC8	Q9ULC8	686
TANGO2	SLC25A1	P53007	666
TANGO2	ARVCF	O00192	665
TANGO2	TRMT2A	Q8IZ69	622
TANGO2	TXNRD2	Q9NNW7	602
TANGO2	PRODH	O43272	585
TANGO2	PRODH	O43272	551
TANGO2	UFD1	Q92890	536
TANGO2	DGCR2	P98153	522
TANGO2	GNB1L	Q9BYB4	488
TANGO2	RANBP1	P43487	471
TANGO2	EMC1	Q8N766	462
TANGO2	SEPTIN5	Q99719	459
TANGO2	SEZ6L	Q9BYH1	456

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TANGO2	SH3GL2	psi-mi:“MI:0915”(physical association)	0.590
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): SH3GL2 (Affinity Capture-MS), BPNT1 (Co-fractionation), PNPO (Co-fractionation), PRDX1 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation), TANGO2 (Co-fractionation)

ESM2 similar proteins: B5FYY5, C9WPN6, F1LTR1, F1QGW6, F6RQL9, O43504, P06730, P20461, P22234, P23258, P29338, P41091, P63073, P63074, P81795, Q0VC00, Q0VCD2, Q13126, Q13888, Q17QI2, Q2KHU8, Q2TBV5, Q2VIR3, Q3MHF7, Q3SZ68, Q4KLK9, Q5HZM6, Q5R797, Q5SP67, Q5ZHS1, Q5ZJQ7, Q5ZMS3, Q66X52, Q6ICL3, Q6NVL5, Q6P1K8, Q8WU67, Q91ZH7, Q969G6, Q99LG2

Diamond homologs: P54797, Q29RZ5, Q6ICL3, Q9VYA8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	13
Uncertain significance	152
Likely benign	238
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075620	NC_000022.10:g.(?20030878)(20049206_?)del	Pathogenic
1312508	NM_152906.7(TANGO2):c.262C>T (p.Arg88Ter)	Pathogenic
1381938	NM_152906.7(TANGO2):c.119G>A (p.Trp40Ter)	Pathogenic
1456250	NC_000022.10:g.(?20030858)(20052185_?)del	Pathogenic
1456565	NM_152906.7(TANGO2):c.607C>T (p.Gln203Ter)	Pathogenic
2106051	NM_152906.7(TANGO2):c.107T>G (p.Leu36Ter)	Pathogenic
224770	NM_152906.5(TANGO2):c.57-1743_*10769del	Pathogenic
224772	NM_152906.7(TANGO2):c.146-3605_451+2245del	Pathogenic
224774	NM_152906.7(TANGO2):c.418C>T (p.Arg140Ter)	Pathogenic
2427422	NC_000022.10:g.(?20039968)(20043556_?)del	Pathogenic
2500728	NC_000022.11:g.20041466_20075200del	Pathogenic
2671601	Single allele	Pathogenic
2710212	NM_152906.7(TANGO2):c.357_358del (p.Phe119fs)	Pathogenic
2732479	NM_152906.7(TANGO2):c.183del (p.Trp61fs)	Pathogenic
2765581	NM_152906.7(TANGO2):c.436dup (p.Ile146fs)	Pathogenic
2829728	NM_152906.7(TANGO2):c.491G>A (p.Trp164Ter)	Pathogenic
3000647	NM_152906.7(TANGO2):c.492G>A (p.Trp164Ter)	Pathogenic
3248139	NC_000022.10:g.(?20039968)(20052185_?)del	Pathogenic
3337652	NM_152906.7(TANGO2):c.250C>T (p.Gln84Ter)	Pathogenic
3343270	NM_152906.7(TANGO2):c.120G>A (p.Trp40Ter)	Pathogenic
3623368	NM_152906.7(TANGO2):c.232C>T (p.Gln78Ter)	Pathogenic
3649351	NM_152906.7(TANGO2):c.183G>A (p.Trp61Ter)	Pathogenic
3697479	NM_152906.7(TANGO2):c.157_160del (p.Glu53fs)	Pathogenic
3906122	GRCh37/hg19 22q11.21(chr22:20030878-20052185)x0	Pathogenic
4056473	Single allele	Pathogenic
4056474	Single allele	Pathogenic
4076039	GRCh37/hg19 22q11.21(chr22:20030823-20053554)x1	Pathogenic
4279120	GRCh37/hg19 22q11.21(chr22:20029992-20053554)x1	Pathogenic
4528934	NC_000022.11:g.20041486_20075431del	Pathogenic
4535883	NC_000022.10:g.(20024378_20030877)(20054688?)del	Pathogenic

SpliceAI

1769 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20043441:GTG:G	donor_gain	1.0000
22:20043443:GGTGA:G	donor_loss	1.0000
22:20043444:G:GA	donor_loss	1.0000
22:20043444:G:GG	donor_gain	1.0000
22:20043445:TGAG:T	donor_loss	1.0000
22:20043446:GAGTC:G	donor_loss	1.0000
22:20052459:CCACA:C	acceptor_loss	1.0000
22:20052460:CACAG:C	acceptor_loss	1.0000
22:20052463:A:AG	acceptor_gain	1.0000
22:20052463:A:C	acceptor_loss	1.0000
22:20052463:AG:A	acceptor_gain	1.0000
22:20052463:AGG:A	acceptor_gain	1.0000
22:20052464:G:A	acceptor_loss	1.0000
22:20052464:G:GG	acceptor_gain	1.0000
22:20052464:GG:G	acceptor_gain	1.0000
22:20052464:GGG:G	acceptor_gain	1.0000
22:20052464:GGGCT:G	acceptor_gain	1.0000
22:20052581:CGAG:C	donor_loss	1.0000
22:20052583:AGGTA:A	donor_loss	1.0000
22:20052584:GGTA:G	donor_loss	1.0000
22:20052585:G:T	donor_loss	1.0000
22:20053431:CTACA:C	acceptor_loss	1.0000
22:20053432:TACAG:T	acceptor_loss	1.0000
22:20053434:CAGGT:C	acceptor_loss	1.0000
22:20053435:AGGTG:A	acceptor_loss	1.0000
22:20053547:CTGAG:C	donor_loss	1.0000
22:20053548:TGAG:T	donor_loss	1.0000
22:20053550:AGGT:A	donor_loss	1.0000
22:20053551:GGTG:G	donor_loss	1.0000
22:20053552:GT:G	donor_loss	1.0000

AlphaMissense

1812 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20053526:T:C	F119L	0.999
22:20053528:C:A	F119L	0.999
22:20053528:C:G	F119L	0.999
22:20043375:G:T	R26M	0.998
22:20052500:T:A	W61R	0.998
22:20052500:T:C	W61R	0.998
22:20043376:G:C	R26S	0.997
22:20043376:G:T	R26S	0.997
22:20053533:T:C	L121P	0.997
22:20043375:G:C	R26T	0.996
22:20043377:G:C	D27H	0.996
22:20043378:A:T	D27V	0.996
22:20061549:C:A	N157K	0.996
22:20061549:C:G	N157K	0.996
22:20043378:A:C	D27A	0.995
22:20064595:G:C	R255P	0.995
22:20043368:G:C	A24P	0.994
22:20043440:A:C	S48R	0.994
22:20043442:T:A	S48R	0.994
22:20043442:T:G	S48R	0.994
22:20052502:G:C	W61C	0.994
22:20052502:G:T	W61C	0.994
22:20052531:C:A	A71E	0.994
22:20052544:C:A	N75K	0.994
22:20052544:C:G	N75K	0.994
22:20053531:C:A	N120K	0.994
22:20053531:C:G	N120K	0.994
22:20061544:A:C	S156R	0.994
22:20061546:C:A	S156R	0.994
22:20061546:C:G	S156R	0.994

dbSNP variants (sampled 300 via entrez): RS1000022300 (22:20015424 G>A,T), RS1000039476 (22:20059806 C>G), RS1000054830 (22:20023163 T>TC), RS1000092855 (22:20016541 G>A,C,T), RS1000167592 (22:20056454 C>T), RS1000256619 (22:20027486 G>A), RS1000298392 (22:20032726 G>A), RS1000431833 (22:20059507 A>G,T), RS1000534842 (22:20051583 G>C), RS1000577636 (22:20061217 C>T), RS1000858715 (22:20028812 A>G), RS1000864865 (22:20066313 A>G), RS1000875570 (22:20061999 T>A), RS1000880530 (22:20035299 C>T), RS1000888770 (22:20066376 T>C)

Disease associations

OMIM: gene MIM:616830 | disease phenotypes: MIM:616878, MIM:209850, MIM:160120

GenCC curated gene-disease

Disease	Classification	Inheritance
recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome	Definitive	Autosomal recessive
metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration	Moderate	Autosomal recessive

Mondo (6): recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (MONDO:0018820), intellectual disability (MONDO:0001071), cardiac rhythm disease (MONDO:0007263), autism (MONDO:0005260), hereditary episodic ataxia (MONDO:0016227), (MONDO:0014812)

Orphanet (3): Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (Orphanet:480864), Hereditary episodic ataxia (Orphanet:211062), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

92 total (30 of 92 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001259	Coma
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001297	Stroke
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001639	Hypertrophic cardiomyopathy
HP:0001657	Prolonged QT interval
HP:0001662	Bradycardia
HP:0001663	Ventricular fibrillation

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004607_190	Plateletcrit	5.000000e-12
GCST005580_284	Intraocular pressure	1.000000e-09
GCST007676_8	3-month functional outcome in ischaemic stroke (modified Rankin score)	5.000000e-06
GCST009413_6	Intraocular pressure	4.000000e-06
GCST009414_16	Central corneal thickness	9.000000e-07
GCST009415_8	Intraocular pressure and central corneal thickness (multi-trait analysis)	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0004695	intraocular pressure measurement
EFO:0009603	stroke outcome severity measurement
EFO:0005213	central corneal thickness

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Acetaminophen	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	increases expression	2
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases expression	1
Arsenic	increases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression	1
Ozone	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00146822	PHASE4	COMPLETED	REFLEx Study (ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance
NCT00187239	PHASE4	COMPLETED	Reduce Ventricular Pacing in Dual Chamber Implantable Cardioverter Defibrillators Using AutoIntrinsic Conduction Search Study
NCT00247533	PHASE4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00282620	PHASE4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00290056	PHASE4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	PHASE4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	PHASE4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	PHASE4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	PHASE4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
NCT01819064	PHASE4	COMPLETED	Heart Rate Response to Atropine Doses Less Than 0.1mg IV to Anesthetized Infants
NCT01834872	PHASE4	UNKNOWN	Safety and Feasibility of Arrhythmia Ablation Using the Amigo Remote Robotic System as Compared With Manual Ablation
NCT01841242	PHASE4	COMPLETED	Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation
NCT01991223	PHASE4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02203630	PHASE4	TERMINATED	Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
NCT02565069	PHASE4	COMPLETED	Identification for the Treatment of Complex Arrhythmias
NCT03273634	PHASE4	COMPLETED	The Effect of Proton Pump Inhibition on Palpitations
NCT03289429	PHASE4	UNKNOWN	Antiarrhythmic and Cardioprotective Effects of Atorvastatin Versus Magnesium Sulfate in Cardiac Valve Replacement Surgery
NCT03895411	PHASE4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05486377	PHASE4	COMPLETED	Remimazolam vs Desflurane for General Anesthesia for Ablation of Arrhythmia
NCT06574555	PHASE4	COMPLETED	Norepinephrine ED90 Bolus After Spinal Anesthesia in Cesarean Section
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000476	PHASE3	COMPLETED	Digitalis Investigation Group (DIG)
NCT00000480	PHASE3	COMPLETED	Multicenter Unsustained Tachycardia Trial (MUSTT)
NCT00000492	PHASE3	COMPLETED	Beta-Blocker Heart Attack Trial (BHAT)
NCT00000502	PHASE3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000517	PHASE3	COMPLETED	Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF)
NCT00000518	PHASE3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00000531	PHASE3	COMPLETED	Antiarrhythmics Versus Implantable Defibrillators (AVID)
NCT00000540	PHASE3	COMPLETED	Coronary Artery Bypass Graft (CABG) Patch Trial
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)