TIGD2

Summary

TIGD2 (tigger transposable element derived 2, HGNC:18333) is a protein-coding gene on chromosome 4q22.1, encoding Tigger transposable element-derived protein 2 (Q4W5G0).

The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known.

Source: NCBI Gene 166815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_145715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18333
Approved symbol	TIGD2
Name	tigger transposable element derived 2
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180346
Ensembl biotype	protein_coding
OMIM	612973
Entrez	166815

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000603357

RefSeq mRNA: 2 — MANE Select: NM_145715 NM_001382380, NM_145715

CCDS: CCDS3633

Canonical transcript exons

ENST00000603357 — 2 exons

Exon	Start	End
ENSE00003469660	89111533	89111883
ENSE00003515242	89112067	89114901

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 90.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1114 / max 157.2748, expressed in 1770 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48823	6.4310	1644
48822	5.4810	1621
48824	0.7631	400
48825	0.4362	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	90.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.91	gold quality
pigmented layer of retina	UBERON:0001782	87.13	gold quality
secondary oocyte	CL:0000655	87.11	gold quality
placenta	UBERON:0001987	86.99	gold quality
palpebral conjunctiva	UBERON:0001812	86.40	gold quality
epithelial cell of pancreas	CL:0000083	85.89	gold quality
liver	UBERON:0002107	85.27	gold quality
oocyte	CL:0000023	85.13	gold quality
right lobe of liver	UBERON:0001114	85.12	gold quality
parotid gland	UBERON:0001831	83.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.83	gold quality
visceral pleura	UBERON:0002401	81.41	gold quality
pancreatic ductal cell	CL:0002079	81.27	silver quality
ileal mucosa	UBERON:0000331	81.26	gold quality
germinal epithelium of ovary	UBERON:0001304	81.21	gold quality
islet of Langerhans	UBERON:0000006	79.29	gold quality
jejunal mucosa	UBERON:0000399	79.10	gold quality
esophagus squamous epithelium	UBERON:0006920	79.08	gold quality
stromal cell of endometrium	CL:0002255	78.94	gold quality
epithelium of mammary gland	UBERON:0003244	77.79	gold quality
saliva-secreting gland	UBERON:0001044	77.70	gold quality
gingival epithelium	UBERON:0001949	77.68	gold quality
mammary duct	UBERON:0001765	77.67	gold quality
epithelium of nasopharynx	UBERON:0001951	77.66	gold quality
mammary gland	UBERON:0001911	77.55	gold quality
thoracic mammary gland	UBERON:0005200	77.54	gold quality
duodenum	UBERON:0002114	77.13	gold quality
minor salivary gland	UBERON:0001830	76.73	gold quality
endothelial cell	CL:0000115	76.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting TIGD2, 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-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-648	98.64	66.13	553
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tigd2	ENSMUSG00000049232
rattus_norvegicus	Tigd2	ENSRNOG00000038449

Paralogs (12): CENPB (ENSG00000125817), TIGD7 (ENSG00000140993), POGK (ENSG00000143157), POGZ (ENSG00000143442), TIGD6 (ENSG00000164296), TIGD4 (ENSG00000169989), TIGD3 (ENSG00000173825), TIGD5 (ENSG00000179886), JRKL (ENSG00000183340), TIGD1 (ENSG00000221944), JRK (ENSG00000234616), (ENSG00000293642)

Protein

Protein identifiers

Tigger transposable element-derived protein 2 — Q4W5G0 (reviewed: Q4W5G0)

All UniProt accessions (2): Q4W5G0, V9HWD1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the tigger transposable element derived protein family.

RefSeq proteins (2): NP_001369309, NP_663761* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004875	DDE_SF_endonuclease_dom	Domain
IPR006600	HTH_CenpB_DNA-bd_dom	Domain
IPR007889	HTH_Psq	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR050863	CenT-Element_Derived	Family

Pfam: PF03184, PF03221, PF04218

UniProt features (8 total): domain 3, DNA-binding region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4W5G0-F1	75.05	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): CHANDRAN_METASTASIS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, WANG_RECURRENT_LIVER_CANCER_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr4q22, PITX2_Q2, NUYTTEN_EZH2_TARGETS_DN, YGCGYRCGC_UNKNOWN, NFAT_Q6, CSHL1_TARGET_GENES, FEV_TARGET_GENES, FOXG1_TARGET_GENES, HES2_TARGET_GENES, HMG20B_TARGET_GENES, KMT2D_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): DNA binding (GO:0003677), nucleic acid binding (GO:0003676)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIGD2	HARBI1	Q96MB7	517
TIGD2	GPRIN3	Q6ZVF9	474
TIGD2	POGK	Q9P215	473
TIGD2	NAIF1	Q69YI7	438
TIGD2	C19orf47	Q8N9M1	433
TIGD2	SMIM13	P0DJ93	428
TIGD2	ACTMAP	Q5BKX5	419
TIGD2	CCSER1	Q9C0I3	416
TIGD2	PYURF	Q96I23	406
TIGD2	EVA1C	P58658	379
TIGD2	ZNF780A	O75290	373
TIGD2	MMRN1	Q13201	370
TIGD2	TTC9B	Q8N6N2	369
TIGD2	ZNF546	Q86UE3	358
TIGD2	CPA6	Q8N4T0	357

IntAct

2 interactions, top by confidence:

A	B	Type	Score
JRKL	TIGD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): TIGD2 (Affinity Capture-MS), TIGD2 (Synthetic Lethality), TIGD2 (Affinity Capture-MS), TIGD2 (Affinity Capture-MS), TIGD2 (Proximity Label-MS), TIGD2 (Proximity Label-MS), TIGD2 (Affinity Capture-MS), TIGD2 (Affinity Capture-MS), TIGD2 (Affinity Capture-MS), TIGD2 (Affinity Capture-MS)

ESM2 similar proteins: A4IFA3, A4Z943, A4Z944, A4Z945, B2RRL2, D3Z4R1, F1NQJ3, O43422, O60108, O60290, O96006, P08770, P0CF97, P12258, P16320, P34601, Q09772, Q0VBL1, Q17RP2, Q3EBC8, Q3YK19, Q49AG3, Q4R6P1, Q4W5G0, Q5SVZ6, Q5SXJ3, Q6EKJ0, Q6NT04, Q6R2W3, Q7L775, Q7M3K2, Q86UP8, Q8BUZ3, Q8IY51, Q8IZ13, Q8TBB0, Q8TCP9, Q8TDG4, Q8VEH5, Q95M72

Diamond homologs: B2RD01, B2RRL2, O75564, Q0VBL1, Q4W5G0, Q60976, Q6NT04, Q9Y4A0, P07199, P27790, P48988, P49451, Q17RP2, Q6B0B8, Q8IY51, Q96MW7, B1WC39, Q499M4, Q8BUZ3, G3MY25, Q53EQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

114 predictions. Top by Δscore:

Variant	Effect	Δscore
4:89111800:A:T	donor_gain	0.9900
4:89111880:GGAG:G	donor_gain	0.9900
4:89111881:GAGG:G	donor_gain	0.9900
4:89112145:GAT:G	donor_gain	0.9700
4:89111879:AGGAG:A	donor_loss	0.9600
4:89111880:GGAGG:G	donor_loss	0.9600
4:89111882:AGGTA:A	donor_loss	0.9600
4:89111883:GGTAG:G	donor_loss	0.9600
4:89111884:G:T	donor_loss	0.9600
4:89111885:T:G	donor_loss	0.9600
4:89112065:A:AG	acceptor_gain	0.9100
4:89112066:G:GG	acceptor_gain	0.9100
4:89111834:G:GT	donor_gain	0.8900
4:89112061:CTTTA:C	acceptor_loss	0.8900
4:89112062:TTTA:T	acceptor_loss	0.8900
4:89112063:TTA:T	acceptor_loss	0.8900
4:89112064:TA:T	acceptor_loss	0.8900
4:89112065:A:AT	acceptor_loss	0.8900
4:89111638:C:G	donor_gain	0.8800
4:89111623:G:GT	donor_gain	0.8600
4:89111834:G:T	donor_gain	0.8600
4:89111799:G:GT	donor_gain	0.8300
4:89112155:A:AG	donor_gain	0.8200
4:89111886:A:C	donor_loss	0.7700
4:89111836:A:T	donor_gain	0.7600
4:89111881:GAG:G	donor_gain	0.7300
4:89111881:G:T	donor_gain	0.7200
4:89111899:C:A	donor_gain	0.6600
4:89111847:C:G	donor_gain	0.6400
4:89111624:A:T	donor_gain	0.6300

AlphaMissense

3480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:89113099:T:A	V42D	0.998
4:89113329:T:C	F119L	0.998
4:89113331:T:A	F119L	0.998
4:89113331:T:G	F119L	0.998
4:89113347:T:A	W125R	0.998
4:89113347:T:C	W125R	0.998
4:89113349:G:C	W125C	0.997
4:89113349:G:T	W125C	0.997
4:89112993:C:A	R7S	0.996
4:89113019:G:C	K15N	0.996
4:89113019:G:T	K15N	0.996
4:89113359:T:C	F129L	0.996
4:89113360:T:C	F129S	0.996
4:89113361:T:A	F129L	0.996
4:89113361:T:G	F129L	0.996
4:89113003:T:C	L10S	0.995
4:89113102:G:C	R43P	0.995
4:89113105:A:T	D44V	0.995
4:89113230:T:A	W86R	0.995
4:89113230:T:C	W86R	0.995
4:89113290:G:C	A106P	0.995
4:89113302:T:C	F110L	0.995
4:89113304:T:A	F110L	0.995
4:89113304:T:G	F110L	0.995
4:89113348:G:C	W125S	0.995
4:89113369:G:C	R132P	0.995
4:89113308:G:C	A112P	0.994
4:89113330:T:C	F119S	0.994
4:89113368:C:A	R132S	0.994
4:89113291:C:A	A106D	0.993

dbSNP variants (sampled 300 via entrez): RS1000129223 (4:89114390 A>G,T), RS1000721064 (4:89110511 C>T), RS1001067770 (4:89110239 T>C), RS1001897578 (4:89111219 C>A,G,T), RS1002330820 (4:89111299 G>A), RS1002615263 (4:89111783 G>A), RS1002798352 (4:89111391 C>T), RS1003617132 (4:89110003 G>A,C), RS1004464659 (4:89111275 G>A,C,T), RS1004799625 (4:89112002 A>C,G), RS1004839210 (4:89110118 G>A), RS1005560150 (4:89110381 T>G), RS1006466446 (4:89113885 G>A,T), RS1006858287 (4:89109418 G>A), RS1007141073 (4:89110621 G>A,C)

Disease associations

OMIM: gene MIM:612973 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003478_2	Hair greying	9.000000e-06
GCST005956_59	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST005957_14	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-06
GCST005962_35	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-08
GCST010002_11	Refractive error	6.000000e-33

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome