TCTA

Summary

TCTA (T cell leukemia translocation altered, HGNC:11692) is a protein-coding gene on chromosome 3p21.31, encoding T-cell leukemia translocation-altered gene protein (P57738). May be required for cellular fusion during osteoclastogenesis.

Involved in negative regulation of osteoclast differentiation and osteoclast fusion. Predicted to be located in membrane.

Source: NCBI Gene 6988 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_022171

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11692
Approved symbol	TCTA
Name	T cell leukemia translocation altered
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145022
Ensembl biotype	protein_coding
OMIM	600690
Entrez	6988

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000273590, ENST00000482193, ENST00000487432, ENST00000488385, ENST00000493381, ENST00000497786, ENST00000908965, ENST00000934100

RefSeq mRNA: 1 — MANE Select: NM_022171 NM_022171

CCDS: CCDS2796

Canonical transcript exons

ENST00000273590 — 3 exons

Exon	Start	End
ENSE00000968360	49412423	49412640
ENSE00001204510	49414820	49416476
ENSE00003558102	49413056	49413110

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9827 / max 1073.5115, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36627	14.0612	1779
36624	4.8599	1586
36626	1.5302	1078
36625	0.5314	294

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	94.00	gold quality
right lobe of thyroid gland	UBERON:0001119	93.71	gold quality
adenohypophysis	UBERON:0002196	93.70	gold quality
left adrenal gland	UBERON:0001234	93.48	gold quality
right adrenal gland cortex	UBERON:0035827	93.47	gold quality
pituitary gland	UBERON:0000007	93.32	gold quality
left lobe of thyroid gland	UBERON:0001120	93.17	gold quality
left adrenal gland cortex	UBERON:0035825	93.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.99	gold quality
adult mammalian kidney	UBERON:0000082	92.86	gold quality
thyroid gland	UBERON:0002046	92.69	gold quality
adrenal cortex	UBERON:0001235	92.48	gold quality
islet of Langerhans	UBERON:0000006	92.45	gold quality
metanephros cortex	UBERON:0010533	92.41	gold quality
spinal cord	UBERON:0002240	92.02	gold quality
right coronary artery	UBERON:0001625	91.94	gold quality
pancreatic ductal cell	CL:0002079	91.75	gold quality
adrenal gland	UBERON:0002369	91.62	gold quality
right frontal lobe	UBERON:0002810	91.62	gold quality
cingulate cortex	UBERON:0003027	91.58	gold quality
anterior cingulate cortex	UBERON:0009835	91.51	gold quality
prefrontal cortex	UBERON:0000451	91.41	gold quality
amygdala	UBERON:0001876	91.27	gold quality
left coronary artery	UBERON:0001626	91.13	gold quality
decidua	UBERON:0002450	91.10	gold quality
putamen	UBERON:0001874	91.08	gold quality
caudate nucleus	UBERON:0001873	91.04	gold quality
nucleus accumbens	UBERON:0001882	91.00	gold quality
mucosa of transverse colon	UBERON:0004991	90.94	gold quality
coronary artery	UBERON:0001621	90.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	413.12
E-CURD-89	no	207.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting TCTA, 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-6748-5P	100.00	65.81	1057
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6852-5P	99.17	66.69	2073

Literature-anchored findings (GeneRIF, showing 3)

• TCTA is a novel protein expressed in synovial tissues of rheumatoid arthritis that regulate human osteoclastogenesis. (PMID:19560569)
• It expressed in synovial tissues from patients with RA and inhibits human osteoclastogenesis. (review) (PMID:20046013)
• TCTA protein has roles in lung cancer cell lines and human osteoclastogenesis [review] (PMID:22174563)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcta	ENSDARG00000044194
mus_musculus	Tcta	ENSMUSG00000039461
rattus_norvegicus	Tcta	ENSRNOG00000048237

Protein

Protein identifiers

T-cell leukemia translocation-altered gene protein — P57738 (reviewed: P57738)

Alternative names: T-cell leukemia translocation-associated gene protein

All UniProt accessions (1): P57738

UniProt curated annotations — full annotation on UniProt →

Function. May be required for cellular fusion during osteoclastogenesis.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous. Highest level of expression in kidney. Present in monocytes, osteoclasts, macrophages, synoviocytes and synovial lining cells (at protein level).

Disease relevance. A chromosomal aberration involving TCTA is associated with T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(1;3)(p34;p21).

Similarity. Belongs to the TCTA family.

RefSeq proteins (1): NP_071503* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016560	TCTA	Family

Pfam: PF15128

UniProt features (12 total): topological domain 3, transmembrane region 2, initiator methionine 1, chain 1, glycosylation site 1, sequence conflict 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57738-F1	66.03	0.11

Functional residue map

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

Post-translational modifications (1): 2

Glycosylation sites (1): 77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, TGCGCANK_UNKNOWN, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GGGTGGRR_PAX4_03, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, NFKB_C, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (2): negative regulation of osteoclast differentiation (GO:0045671), osteoclast fusion (GO:0072675)

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
syncytium formation by cell-cell fusion	1
multinuclear osteoclast differentiation	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCTA	GPR25	O00155	508
TCTA	AK9	Q5TCS8	504
TCTA	OTOP3	Q7RTS5	484
TCTA	GGTLC3	B5MD39	447
TCTA	RIIAD1	A6NNX1	430
TCTA	BLOC1S3	Q6QNY0	422
TCTA	GGT2P	P36268	396
TCTA	ZNRF2	Q8NHG8	390
TCTA	EEIG2	Q5T8I3	384
TCTA	TRABD2B	A6NFA1	371
TCTA	ATP6V1F	Q16864	365
TCTA	TRAPPC6B	Q86SZ2	348
TCTA	GUCY2C	P25092	323
TCTA	MAGEB18	Q96M61	320
TCTA	GMPS	P49915	315

IntAct

16 interactions, top by confidence:

A	B	Type	Score
YIPF6	TCTA	psi-mi:“MI:0915”(physical association)	0.560
TCTA	SLC35A1	psi-mi:“MI:0915”(physical association)	0.560
BMP10	TCTA	psi-mi:“MI:0915”(physical association)	0.560
TCTA	CMTM7	psi-mi:“MI:0915”(physical association)	0.560
TCTA	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
TCTA	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
TCTA	ATXN1	psi-mi:“MI:0915”(physical association)	0.370
SMAD4	TCTA	psi-mi:“MI:0915”(physical association)	0.370
SLC35A1	TCTA	psi-mi:“MI:0915”(physical association)	0.000
BMP10	TCTA	psi-mi:“MI:0915”(physical association)	0.000
CMTM7	TCTA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): CMTM7 (Two-hybrid), BMP10 (Two-hybrid), SLC35A1 (Two-hybrid), YIPF6 (Two-hybrid), TCTA (Two-hybrid), TCTA (Affinity Capture-RNA), TCTA (Two-hybrid), TCTA (Two-hybrid)

ESM2 similar proteins: A0A1B0GTK4, A0A1B0GTK5, A0JNL8, A2RUT3, A4D250, B2KGE5, F1MQW7, F2Z3F1, F5HHT4, O93195, O95411, P04610, P05905, P0C733, P0C7M3, P0DP71, P16722, P17758, P47939, P47940, P57738, Q0VD86, Q1HVB5, Q1RN00, Q1X6Y7, Q1X6Z1, Q1X6Z2, Q3ZN08, Q5PR19, Q5PXH1, Q5TC04, Q5TEZ4, Q64902, Q66669, Q66HF0, Q67863, Q6DGF6, Q6UYE1, Q7L4S7, Q8AZJ3

Diamond homologs: A4IHD1, P57738, Q3KPU7, Q5EAA5, Q5R7E2, Q5XIF1, Q6DGY3, Q8VEA7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

240 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49412565:GTGT:G	donor_gain	0.9900
3:49412566:TGTT:T	donor_gain	0.9900
3:49412568:T:G	donor_gain	0.9800
3:49412625:T:TA	donor_gain	0.9700
3:49412636:TCCAG:T	donor_loss	0.9700
3:49412637:CCAG:C	donor_loss	0.9700
3:49412638:CAGGT:C	donor_loss	0.9700
3:49412639:AGG:A	donor_loss	0.9700
3:49412640:GGTGA:G	donor_loss	0.9700
3:49412641:G:A	donor_loss	0.9700
3:49412642:T:G	donor_loss	0.9700
3:49413108:GTG:G	donor_gain	0.9500
3:49412626:T:TA	donor_gain	0.9400
3:49413111:G:GG	donor_gain	0.9400
3:49413112:T:TG	donor_loss	0.9400
3:49413113:G:GG	donor_loss	0.9400
3:49413114:A:AC	donor_loss	0.9400
3:49414865:G:T	donor_gain	0.9400
3:49412567:GTTA:G	donor_gain	0.9300
3:49413115:G:C	donor_loss	0.9300
3:49414818:AG:A	acceptor_gain	0.9100
3:49414819:GG:G	acceptor_gain	0.9100
3:49414819:GGGAA:G	acceptor_gain	0.8900
3:49412563:T:A	donor_gain	0.8800
3:49412794:C:G	donor_gain	0.8800
3:49414814:TTTCA:T	acceptor_loss	0.8600
3:49414815:TTCA:T	acceptor_loss	0.8600
3:49414816:TCAG:T	acceptor_loss	0.8600
3:49414817:CAGG:C	acceptor_loss	0.8600
3:49414818:AGG:A	acceptor_gain	0.8600

AlphaMissense

652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49412571:A:C	S49R	0.998
3:49412573:T:A	S49R	0.998
3:49412573:T:G	S49R	0.998
3:49412559:T:A	W45R	0.997
3:49412559:T:C	W45R	0.997
3:49412511:T:A	W29R	0.989
3:49412511:T:C	W29R	0.989
3:49412513:G:C	W29C	0.988
3:49412513:G:T	W29C	0.988
3:49412595:T:A	W57R	0.988
3:49412595:T:C	W57R	0.988
3:49412500:T:C	F25S	0.985
3:49412597:G:C	W57C	0.982
3:49412597:G:T	W57C	0.982
3:49412593:C:A	A56E	0.981
3:49412575:T:C	L50P	0.978
3:49412551:T:G	L42R	0.976
3:49412580:G:C	G52R	0.975
3:49412575:T:A	L50H	0.972
3:49412499:T:C	F25L	0.971
3:49412501:C:A	F25L	0.971
3:49412501:C:G	F25L	0.971
3:49412575:T:G	L50R	0.971
3:49412607:G:T	G61W	0.968
3:49412541:T:C	F39L	0.967
3:49412543:C:A	F39L	0.967
3:49412543:C:G	F39L	0.967
3:49412551:T:C	L42P	0.967
3:49412617:T:A	V64E	0.965
3:49412584:T:A	I53N	0.964

dbSNP variants (sampled 300 via entrez): RS1000203507 (3:49412305 C>G,T), RS1000291791 (3:49411270 T>A), RS1000322619 (3:49411534 C>T), RS1000840696 (3:49415169 T>G), RS1001008481 (3:49411271 C>A,G), RS1001358351 (3:49415458 G>A), RS1002520524 (3:49410588 T>C), RS1003348157 (3:49415141 G>A), RS1003787257 (3:49415591 C>G,T), RS1004287291 (3:49412382 G>A,T), RS1004302454 (3:49416277 C>T), RS1004754296 (3:49414988 T>G), RS1004903505 (3:49411672 T>C), RS1005495105 (3:49411853 G>A), RS1005580526 (3:49411803 G>A)

Disease associations

OMIM: gene MIM:600690 | disease phenotypes: MIM:605899

GenCC curated gene-disease

Mondo (1): glycine encephalopathy (MONDO:0011612)

Orphanet (1): Glycine encephalopathy (Orphanet:407)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002774_6	Cognitive function	8.000000e-06
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005196_105	Coronary artery disease	1.000000e-08
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST009391_1716	Metabolite levels	5.000000e-06
GCST009524_332	Household income (MTAG)	1.000000e-13
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0010341	cholesteryl ester 16:0 measurement
EFO:0009695	household income
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
M-VAC protocol	increases response to substance	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
ICG 001	decreases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diuron	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Isotretinoin	decreases expression	1
Cadmium Chloride	increases expression, increases abundance	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan