TRABD2A

Summary

TRABD2A (TraB domain containing 2A, HGNC:27013) is a protein-coding gene on chromosome 2p11.2, encoding Metalloprotease TIKI1 (Q86V40). Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins.

Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in negative regulation of Wnt signaling pathway and proteolysis. Located in organelle membrane and plasma membrane.

Source: NCBI Gene 129293 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001277053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27013
Approved symbol	TRABD2A
Name	TraB domain containing 2A
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	TIKI1
Ensembl gene	ENSG00000186854
Ensembl biotype	protein_coding
OMIM	614912
Entrez	129293

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000335459, ENST00000409133, ENST00000409520, ENST00000436322, ENST00000460991, ENST00000474298, ENST00000479944, ENST00000489999, ENST00000495990, ENST00000496500, ENST00000889653, ENST00000889654, ENST00000915223, ENST00000966430, ENST00000966431

RefSeq mRNA: 3 — MANE Select: NM_001277053 NM_001080824, NM_001277053, NM_001307978

CCDS: CCDS46349, CCDS62946, CCDS77428

Canonical transcript exons

ENST00000409520 — 7 exons

Exon	Start	End
ENSE00001332103	84821666	84822100
ENSE00003499954	84832055	84832145
ENSE00003505277	84841861	84842007
ENSE00003514957	84823953	84824204
ENSE00003687307	84839149	84839323
ENSE00003841855	84880932	84881084
ENSE00003889565	84870225	84870785

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6904 / max 281.3734, expressed in 1062 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29362	1.6302	426
29365	1.0617	285
29364	0.5329	95
29363	0.4036	199
29366	0.2855	80
29370	0.2774	133
29369	0.2438	98
29371	0.1766	57
29367	0.0788	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.79	gold quality
rectum	UBERON:0001052	95.73	gold quality
ileal mucosa	UBERON:0000331	95.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.15	gold quality
colonic mucosa	UBERON:0000317	92.93	gold quality
left testis	UBERON:0004533	91.19	gold quality
right testis	UBERON:0004534	91.03	gold quality
granulocyte	CL:0000094	88.02	gold quality
transverse colon	UBERON:0001157	87.34	gold quality
left ovary	UBERON:0002119	87.22	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.13	gold quality
testis	UBERON:0000473	87.08	gold quality
left ventricle myocardium	UBERON:0006566	86.97	gold quality
colonic epithelium	UBERON:0000397	86.78	gold quality
blood	UBERON:0000178	86.25	gold quality
vermiform appendix	UBERON:0001154	84.78	gold quality
right ovary	UBERON:0002118	84.68	gold quality
lymph node	UBERON:0000029	83.18	gold quality
ovary	UBERON:0000992	82.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.59	gold quality
caecum	UBERON:0001153	81.52	gold quality
myocardium	UBERON:0002349	79.79	gold quality
small intestine	UBERON:0002108	79.45	gold quality
large intestine	UBERON:0000059	79.34	gold quality
intestine	UBERON:0000160	79.34	gold quality
colon	UBERON:0001155	78.87	gold quality
sperm	CL:0000019	78.54	silver quality
stromal cell of endometrium	CL:0002255	77.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.91	gold quality
kidney epithelium	UBERON:0004819	76.14	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	43.02
E-ANND-3	yes	8.26
E-MTAB-7606	no	197.62
E-MTAB-7008	no	21.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting TRABD2A, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6724-5P	96.41	63.11	507

Literature-anchored findings (GeneRIF, showing 3)

• Tiki1 antagonizes Wnt function in embryos and human cells via a TIKI homology domain that is conserved from bacteria to mammals and acts likely as a protease to cleave eight amino-terminal residues of a Wnt protein, resulting in oxidized Wnt oligomers that exhibit normal secretion but minimized receptor-binding capability. (PMID:22726442)
• Metalloprotease TRABD2A Restriction of HIV-1 Production in Monocyte-Derived Dendritic Cells. (PMID:31282173)
• Inhibition of Metalloprotease TRABD2A Facilitates the Study of HIV-1 Replication in Resting CD4(+) T Cells. (PMID:31801864)

Cross-species orthologs

0 orthologs

Paralogs (1): TRABD2B (ENSG00000269113)

Protein

Protein identifiers

Metalloprotease TIKI1 — Q86V40 (reviewed: Q86V40)

Alternative names: TRAB domain-containing protein 2A

All UniProt accessions (2): C9IYB5, Q86V40

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required for head formation.

Subcellular location. Cell membrane.

Cofactor. Divalent metal cations. Mn(2+) or Co(2+).

Miscellaneous. Was named TIKI in reference to large-headed humanoid in Polynesian mythology.

Similarity. Belongs to the TIKI family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86V40-1	1	yes
Q86V40-2	2

RefSeq proteins (3): NP_001074293, NP_001263982, NP_001294907 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002816	TraB/PrgY/GumN_fam	Family
IPR040230	TIKI1/2-like	Family

Pfam: PF01963

UniProt features (16 total): glycosylation site 4, sequence variant 3, topological domain 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V40-F1	69.50	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (4): 336, 220, 229, 278

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, ZHAN_MULTIPLE_MYELOMA_HP_UP, LEE_EARLY_T_LYMPHOCYTE_DN, GOBP_HEAD_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, chr2p11, GOBP_NEGATIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_PROTEOLYSIS, GOMF_WNT_PROTEIN_BINDING, GOMF_PEPTIDASE_ACTIVITY, ARNT2_TARGET_GENES

GO Biological Process (5): proteolysis (GO:0006508), Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), positive regulation of protein-containing complex assembly (GO:0031334), head development (GO:0060322)

GO Molecular Function (7): endopeptidase activity (GO:0004175), metalloendopeptidase activity (GO:0004222), Wnt-protein binding (GO:0017147), metal ion binding (GO:0046872), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), organelle membrane (GO:0031090)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
membrane	2
protein metabolic process	1
cell surface receptor signaling pathway	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
anatomical structure development	1
endopeptidase activity	1
metallopeptidase activity	1
protein binding	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cell periphery	1
cellular anatomical structure	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

196 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRABD2A	APCDD1	Q8J025	571
TRABD2A	TPBG	Q13641	507
TRABD2A	TRABD	Q9H4I3	487
TRABD2A	NOTUM	Q6P988	450
TRABD2A	SOST	Q9BQB4	443
TRABD2A	NDP	Q00604	434
TRABD2A	WIF1	Q9Y5W5	408
TRABD2A	DKK4	Q9UBT3	405
TRABD2A	DKK1	O94907	381
TRABD2A	DKK2	Q9UBU2	353
TRABD2A	GAB4	Q2WGN9	320
TRABD2A	FAM78B	Q5VT40	314
TRABD2A	RSPO1	Q2MKA7	308
TRABD2A	SLC5A9	Q2M3M2	304
TRABD2A	SLITRK6	Q9H5Y7	303

IntAct

2 interactions, top by confidence:

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

BioGRID (1): TRABD2A (Affinity Capture-RNA)

ESM2 similar proteins: A0A8C2LVE3, A0MGZ5, A0MGZ7, A4IID1, A5D7I4, A9X1C8, O08889, O12971, O60243, O93336, O97583, P0DJQ9, P52849, P52850, P61642, P69478, P97464, Q16394, Q56UJ5, Q5IGR7, Q5IGR8, Q5R621, Q5RBC3, Q5U4X8, Q6GQK9, Q6KFX9, Q6ZXD2, Q76KB1, Q76KB2, Q7LFX5, Q7LGA3, Q7T3S3, Q800H9, Q80UW0, Q86V40, Q8CHI9, Q8IZP7, Q8R3H7, Q91XQ5, Q91ZB4

Diamond homologs: A6NFA1, A7RX69, B1ATG9, E7F4V6, E7F6V0, F6PTN1, I1FQB6, P0DJQ9, Q17678, Q86V40

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2352 predictions. Top by Δscore:

Variant	Effect	Δscore
2:84822101:C:CC	acceptor_gain	1.0000
2:84832053:A:AC	donor_gain	1.0000
2:84832054:C:CC	donor_gain	1.0000
2:84839140:ACTAC:A	donor_loss	1.0000
2:84839143:ACT:A	donor_loss	1.0000
2:84839144:CTCA:C	donor_loss	1.0000
2:84839145:T:TC	donor_loss	1.0000
2:84839146:C:CC	donor_loss	1.0000
2:84839147:A:AC	donor_gain	1.0000
2:84839148:C:CA	donor_loss	1.0000
2:84839148:C:CC	donor_gain	1.0000
2:84839148:CCAG:C	donor_gain	1.0000
2:84839330:CAAAA:C	acceptor_gain	1.0000
2:84839331:A:T	acceptor_gain	1.0000
2:84839334:A:AC	acceptor_gain	1.0000
2:84841856:CTCA:C	donor_loss	1.0000
2:84841857:TCAC:T	donor_loss	1.0000
2:84841858:CACC:C	donor_loss	1.0000
2:84841859:A:T	donor_loss	1.0000
2:84841860:C:A	donor_loss	1.0000
2:84843646:A:C	acceptor_gain	1.0000
2:84870219:TCTTA:T	donor_loss	1.0000
2:84870220:CTTA:C	donor_loss	1.0000
2:84870221:TTA:T	donor_loss	1.0000
2:84870222:TA:T	donor_loss	1.0000
2:84870223:A:AC	donor_gain	1.0000
2:84870224:C:CA	donor_loss	1.0000
2:84870224:C:CC	donor_gain	1.0000
2:84870781:CTTTG:C	acceptor_gain	1.0000
2:84870782:TTTG:T	acceptor_gain	1.0000

AlphaMissense

3291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:84870483:C:A	W137C	0.998
2:84870483:C:G	W137C	0.998
2:84870485:A:G	W137R	0.998
2:84870485:A:T	W137R	0.998
2:84870693:C:A	W67C	0.998
2:84870693:C:G	W67C	0.998
2:84870308:C:G	A196P	0.997
2:84870416:A:G	W160R	0.997
2:84870416:A:T	W160R	0.997
2:84870724:C:T	G57D	0.997
2:84870761:A:G	W45R	0.997
2:84870761:A:T	W45R	0.997
2:84841982:A:G	L232P	0.996
2:84870307:G:T	A196D	0.996
2:84870331:A:G	L188S	0.996
2:84870414:C:A	W160C	0.996
2:84870414:C:G	W160C	0.996
2:84841982:A:T	L232H	0.995
2:84870291:T:A	K201N	0.995
2:84870291:T:G	K201N	0.995
2:84870370:A:G	L175P	0.995
2:84870395:A:G	W167R	0.995
2:84870395:A:T	W167R	0.995
2:84870526:A:G	L123P	0.995
2:84870669:C:A	K75N	0.995
2:84870669:C:G	K75N	0.995
2:84870695:A:G	W67R	0.995
2:84870695:A:T	W67R	0.995
2:84870725:C:G	G57R	0.995
2:84870759:C:A	W45C	0.995

dbSNP variants (sampled 300 via entrez): RS1000007927 (2:84840794 T>C), RS1000010704 (2:84833347 A>T), RS1000044367 (2:84873848 C>T), RS1000100003 (2:84869242 T>C), RS1000190569 (2:84840228 G>A), RS1000200994 (2:84830356 A>G), RS1000289764 (2:84833098 C>T), RS1000332562 (2:84845166 C>G,T), RS1000448678 (2:84845331 A>G), RS1000453614 (2:84882555 C>G), RS1000489470 (2:84862308 G>A,T), RS1000607285 (2:84849294 C>G,T), RS1000677142 (2:84850764 A>G), RS1000727905 (2:84852828 A>G), RS1000783776 (2:84844012 G>T)

Disease associations

OMIM: gene MIM:614912 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008310_2	Cardiac Troponin-T levels	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases mutagenesis	2
Dexamethasone	increases expression, affects cotreatment	2
Aflatoxin B1	increases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	increases expression	1
Temozolomide	decreases expression	1
Aldehydes	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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