TCL1B

Summary

TCL1B (TCL1 family AKT coactivator B, HGNC:11649) is a protein-coding gene on chromosome 14q32.13, encoding T-cell leukemia/lymphoma protein 1B (O95988). Enhances the phosphorylation and activation of AKT1 and AKT2.

Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in intracellular signal transduction.

Source: NCBI Gene 9623 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_004918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11649
Approved symbol	TCL1B
Name	TCL1 family AKT coactivator B
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	TML1
Ensembl gene	ENSG00000213231
Ensembl biotype	protein_coding
OMIM	603769
Entrez	9623

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000340722, ENST00000464815, ENST00000556665, ENST00000916734, ENST00000916735, ENST00000916736

RefSeq mRNA: 1 — MANE Select: NM_004918 NM_004918

CCDS: CCDS32151

Canonical transcript exons

ENST00000340722 — 4 exons

Exon	Start	End
ENSE00001875989	95686426	95686629
ENSE00003433526	95691931	95692628
ENSE00003473394	95691268	95691336
ENSE00003581427	95690736	95690906

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 89.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3719 / max 174.9637, expressed in 97 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141300	0.3409	93
141301	0.0310	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.23	gold quality
granulocyte	CL:0000094	68.38	gold quality
lymph node	UBERON:0000029	63.39	gold quality
testis	UBERON:0000473	58.25	gold quality
placenta	UBERON:0001987	58.18	gold quality
left testis	UBERON:0004533	57.47	gold quality
tonsil	UBERON:0002372	56.74	gold quality
right testis	UBERON:0004534	56.32	gold quality
bone marrow cell	CL:0002092	54.13	gold quality
spleen	UBERON:0002106	54.05	gold quality
blood	UBERON:0000178	53.66	gold quality
bone marrow	UBERON:0002371	52.22	gold quality
vermiform appendix	UBERON:0001154	50.34	gold quality
colonic epithelium	UBERON:0000397	45.32	gold quality
mucosa of transverse colon	UBERON:0004991	45.30	gold quality
gall bladder	UBERON:0002110	43.80	gold quality
leukocyte	CL:0000738	42.42	gold quality
monocyte	CL:0000576	39.95	silver quality
skeletal muscle tissue	UBERON:0001134	36.55	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right coronary artery	UBERON:0001625	34.96	gold quality
muscle tissue	UBERON:0002385	34.58	gold quality
adrenal tissue	UBERON:0018303	34.29	gold quality
liver	UBERON:0002107	33.25	silver quality
small intestine	UBERON:0002108	33.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	32.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting TCL1B, 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-4481	100.00	66.42	1669
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-6894-3P	96.73	65.64	798

Literature-anchored findings (GeneRIF, showing 1)

• subcellular localization of activated AKT is dependent on TCL1B expression in estrogen receptor- and progesterone receptor-expressing breast cancer (PMID:20228224)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tcl1b5	ENSMUSG00000000701
mus_musculus	Tcl1b2	ENSMUSG00000060863
mus_musculus	Tcl1b1	ENSMUSG00000066359
mus_musculus	Tcl1b3	ENSMUSG00000068940
mus_musculus	Tcl1b4	ENSMUSG00000079007

Paralogs (2): TCL1A (ENSG00000100721), MTCP1 (ENSG00000214827)

Protein

Protein identifiers

T-cell leukemia/lymphoma protein 1B — O95988 (reviewed: O95988)

Alternative names: Oncogene TCL-1B, SYN-1, Syncytiotrophoblast-specific protein, TCL1/MTCP1-like protein 1

All UniProt accessions (1): O95988

UniProt curated annotations — full annotation on UniProt →

Function. Enhances the phosphorylation and activation of AKT1 and AKT2.

Subunit / interactions. Interacts with AKT1 and AKT2 (via PH domain). Does not interact with AKT3.

Tissue specificity. Expressed in a variety of tissues including placenta and testis.

Miscellaneous. Activated in chronic T-cell leukemias (T-CLL) carrying rearrangements of the 14q32.1 region.

Similarity. Belongs to the TCL1 family.

RefSeq proteins (1): NP_004909* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004832	TCL1_MTCP1	Family
IPR036672	TCL1_MTCP1_sf	Homologous_superfamily

Pfam: PF01840

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95988-F1	79.37	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, HATADA_METHYLATED_IN_LUNG_CANCER_DN, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOMF_KINASE_ACTIVATOR_ACTIVITY, chr14q32, WORSCHECH_TUMOR_REJECTION_UP, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVATOR_ACTIVITY, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_KINASE_BINDING, SU_PANCREAS, BRUINS_UVC_RESPONSE_EARLY_LATE, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, DCA_UP.V1_DN, IWANAGA_CARCINOGENESIS_BY_KRAS_PTEN_UP

GO Biological Process (1): intracellular signal transduction (GO:0035556)

GO Molecular Function (3): protein kinase binding (GO:0019901), protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	1
signal transduction	1
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
binding	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCL1B	PRDM14	Q9GZV8	641
TCL1B	AKT1	P31749	641
TCL1B	CD5	P06127	631
TCL1B	DNMT3A	Q9Y6K1	624
TCL1B	ESRRB	O95718	620
TCL1B	IGHV4-38-2	P0DP08	610
TCL1B	SIK2	Q9H0K1	547
TCL1B	KDM3A	Q9Y4C1	547
TCL1B	KDM4C	Q9H3R0	546
TCL1B	NANOG	Q9H9S0	543
TCL1B	CLEC4C	Q8WTT0	543
TCL1B	TBX3	O15119	540
TCL1B	BTK	Q06187	540
TCL1B	ROR1	Q01973	530
TCL1B	AKT2	P31751	514

IntAct

54 interactions, top by confidence:

A	B	Type	Score
LSM1	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
LSM5	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
LSM7	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
SNRPG	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
BAG4	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	TCL1B	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	MARK1	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	ZNF330	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	MEIS3	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	LSM5	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	PLEKHA3	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	LSM7	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	SNRPG	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	EFCAB2	psi-mi:“MI:0915”(physical association)	0.560
TCL1B	MED14	psi-mi:“MI:0914”(association)	0.530
TCL1B	MAGI3	psi-mi:“MI:0914”(association)	0.350
TCL1B	BAG4	psi-mi:“MI:0915”(physical association)	0.000
TCL1B	GLRX3	psi-mi:“MI:0915”(physical association)	0.000
TCL1B	PNMA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (88): ACAD11 (Affinity Capture-MS), MED13 (Affinity Capture-MS), HPS3 (Affinity Capture-MS), MED1 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), STRN4 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MAGI3 (Affinity Capture-MS), HPS6 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), MED23 (Affinity Capture-MS), MED4 (Affinity Capture-MS), MED16 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS)

ESM2 similar proteins: A0K4L0, A1BI65, A1VM62, A1WLP2, A6TG77, A7N128, A8GYI0, A9AH76, A9KBK6, A9MIA3, A9MZA2, A9N8X1, B0RRA0, B1JVU9, B1YTD6, B2FNX7, B2SVL7, B4SQT4, B4SZX0, B4TBW0, B5BJ27, B5F000, B5FP17, B5QWW2, B5RFE5, B5XZI4, C1DAD5, D2Z024, O82258, O95988, P04866, P55415, Q01RT2, Q0A777, Q1BZ40, Q1GFL4, Q21YC5, Q2NAM2, Q2P0V7, Q39JJ5

Diamond homologs: O95988, P56278, P56280, Q60945, P56279

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TCL1B	up-regulates	AKT	binding
TCL1B	up-regulates	AKT1	binding
TCL1B	up-regulates	AKT2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

574 predictions. Top by Δscore:

Variant	Effect	Δscore
14:95686553:G:T	donor_gain	1.0000
14:95690855:G:GT	donor_gain	1.0000
14:95691313:A:T	donor_gain	1.0000
14:95686544:A:G	donor_gain	0.9900
14:95686549:G:GT	donor_gain	0.9900
14:95686553:G:GT	donor_gain	0.9900
14:95686574:T:TA	donor_gain	0.9900
14:95686625:GCAGA:G	donor_gain	0.9900
14:95686628:GA:G	donor_gain	0.9900
14:95686630:G:GG	donor_gain	0.9900
14:95690724:T:TA	acceptor_gain	0.9900
14:95690734:A:AG	acceptor_gain	0.9900
14:95690735:G:GC	acceptor_gain	0.9900
14:95690735:GT:G	acceptor_gain	0.9900
14:95690735:GTAT:G	acceptor_gain	0.9900
14:95691327:G:GT	donor_gain	0.9900
14:95690732:TCAGT:T	acceptor_loss	0.9800
14:95690733:CA:C	acceptor_loss	0.9800
14:95690734:A:AT	acceptor_loss	0.9800
14:95690734:AGTAT:A	acceptor_gain	0.9800
14:95690735:GTATG:G	acceptor_gain	0.9800
14:95691266:A:AG	acceptor_gain	0.9800
14:95691267:G:GG	acceptor_gain	0.9800
14:95690855:G:T	donor_gain	0.9700
14:95691267:GATT:G	acceptor_gain	0.9700
14:95691312:G:GT	donor_gain	0.9700
14:95686550:A:T	donor_gain	0.9600
14:95686593:GC:G	donor_gain	0.9600
14:95690735:GTA:G	acceptor_gain	0.9600
14:95690886:G:T	donor_gain	0.9600

AlphaMissense

827 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:95690859:T:C	Y96H	0.983
14:95690885:G:C	W104C	0.980
14:95690885:G:T	W104C	0.980
14:95690860:A:C	Y96S	0.979
14:95690835:T:A	W88R	0.976
14:95690835:T:C	W88R	0.976
14:95690859:T:G	Y96D	0.975
14:95686563:G:C	W32C	0.974
14:95686563:G:T	W32C	0.974
14:95690837:G:C	W88C	0.973
14:95690837:G:T	W88C	0.973
14:95690883:T:A	W104R	0.967
14:95690883:T:C	W104R	0.967
14:95690860:A:G	Y96C	0.966
14:95691293:T:C	L120P	0.965
14:95686561:T:A	W32R	0.956
14:95686561:T:C	W32R	0.956
14:95690836:G:C	W88S	0.952
14:95691287:T:C	L118P	0.946
14:95686537:T:G	Y24D	0.945
14:95690859:T:A	Y96N	0.945
14:95691293:T:A	L120Q	0.938
14:95690884:G:C	W104S	0.937
14:95690755:T:A	V61E	0.936
14:95686543:G:C	D26H	0.933
14:95690761:T:C	L63S	0.931
14:95686537:T:A	Y24N	0.926
14:95686532:G:A	G22D	0.901
14:95686531:G:C	G22R	0.899
14:95690827:C:A	P85H	0.895

dbSNP variants (sampled 300 via entrez): RS1000018427 (14:95691683 G>A), RS1000206699 (14:95692300 A>G), RS1000507741 (14:95686219 C>A), RS1000540314 (14:95686068 G>C), RS1000977308 (14:95690673 T>C,G), RS1002216314 (14:95684591 C>T), RS1002221872 (14:95689540 A>C,T), RS1002604954 (14:95691054 T>C), RS1002615055 (14:95684799 C>A), RS1004105272 (14:95689286 C>T), RS1004184016 (14:95685139 C>T), RS1004279409 (14:95684868 T>C), RS1005316088 (14:95687070 A>G), RS1005452756 (14:95689091 C>T), RS1005880191 (14:95693077 G>C)

Disease associations

OMIM: gene MIM:603769 | 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
GCST010002_159	Refractive error	9.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	decreases expression, increases expression	2
Estradiol	increases expression, increases activity, increases localization, increases phosphorylation, increases reaction (+1 more)	2
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Endosulfan	decreases expression	1
Valproic Acid	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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