TBPL2

Summary

TBPL2 (TATA-box binding protein like 2, HGNC:19841) is a protein-coding gene on chromosome 14q22.3, encoding TATA box-binding protein-like 2 (Q6SJ96). Transcription factor required in complex with TAF3 for the differentiation of myoblasts into myocytes.

Predicted to enable RNA polymerase II general transcription initiation factor activity. Predicted to be involved in DNA-templated transcription initiation. Located in cytoplasm and nucleus.

Source: NCBI Gene 387332 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 1 total
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_199047

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19841
Approved symbol	TBPL2
Name	TATA-box binding protein like 2
Location	14q22.3
Locus type	gene with protein product
Status	Approved
Aliases	TRF3, TBP2
Ensembl gene	ENSG00000182521
Ensembl biotype	protein_coding
OMIM	608964
Entrez	387332

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000247219, ENST00000556755

RefSeq mRNA: 1 — MANE Select: NM_199047 NM_199047

CCDS: CCDS9724

Canonical transcript exons

ENST00000247219 — 7 exons

Exon	Start	End
ENSE00000867271	55433630	55433721
ENSE00000940873	55435847	55435934
ENSE00001147383	55436561	55437018
ENSE00001296862	55414210	55414455
ENSE00001366065	55440396	55440616
ENSE00001607727	55428807	55428974
ENSE00001643126	55424159	55424253

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 84.22.

Top tissues by expression

91 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	84.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.12	gold quality
sural nerve	UBERON:0015488	69.49	gold quality
stromal cell of endometrium	CL:0002255	56.03	gold quality
skeletal muscle tissue	UBERON:0001134	49.88	gold quality
cortical plate	UBERON:0005343	48.20	gold quality
bone marrow cell	CL:0002092	47.93	silver quality
tonsil	UBERON:0002372	47.92	gold quality
muscle tissue	UBERON:0002385	46.59	gold quality
urinary bladder	UBERON:0001255	44.23	gold quality
mucosa of transverse colon	UBERON:0004991	43.73	silver quality
ganglionic eminence	UBERON:0004023	43.10	gold quality
bone marrow	UBERON:0002371	42.74	silver quality
mucosa of stomach	UBERON:0001199	41.69	silver quality
right coronary artery	UBERON:0001625	41.49	gold quality
right uterine tube	UBERON:0001302	40.48	silver quality
ventricular zone	UBERON:0003053	40.10	gold quality
rectum	UBERON:0001052	39.18	gold quality
calcaneal tendon	UBERON:0003701	39.02	gold quality
smooth muscle tissue	UBERON:0001135	38.36	gold quality
cortex of kidney	UBERON:0001225	38.22	silver quality
endometrium	UBERON:0001295	37.85	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
blood	UBERON:0000178	36.76	gold quality
apex of heart	UBERON:0002098	35.96	gold quality
right ovary	UBERON:0002118	35.67	gold quality
ovary	UBERON:0000992	34.76	gold quality
kidney	UBERON:0002113	34.58	silver quality
liver	UBERON:0002107	34.51	silver quality
body of uterus	UBERON:0009853	34.25	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
AFM
AP1
CDKN1A
CDX4
LPL
MAPK8
PAM
POLI
TBP
TXN
TXNIP

miRNA regulators (miRDB)

10 targeting TBPL2, 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-4267	99.96	66.53	2368
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-1277-3P	93.47	68.97	156
HSA-MIR-1249-3P	90.34	67.26	42
HSA-MIR-6726-3P	83.39	62.13	46

Literature-anchored findings (GeneRIF, showing 6)

• TRF3 is a nuclear protein that is present in all human and mouse tissues and cell lines examined (PMID:14634207)
• Here we report that differentiation of myoblast to myotubes involves the disruption of the canonical holo-TFIID and replacement by a novel TRF3/TAF3 (TBP-related factor 3/TATA-binding protein-associated factor 3) complex. (PMID:17704303)
• study indicates that the TBP2 gene is not responsible for idiopathic primary ovarian insufficiency in the Chinese Han population (PMID:27642674)
• TATA box-binding protein-related factor 3 drives the mesendoderm specification of human embryonic stem cells by globally interacting with the TATA box of key mesendodermal genes. (PMID:32448362)
• A recurrent mutation in TBPL2 causes diminished ovarian reserve and female infertility. (PMID:33541821)
• A homozygous missense mutation in TBPL2 is associated with oocyte maturation arrest and degeneration. (PMID:33966269)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbpl2	ENSDARG00000097302
mus_musculus	Tbpl2	ENSMUSG00000061809
rattus_norvegicus	Tbpl2	ENSRNOG00000033682

Paralogs (2): TBPL1 (ENSG00000028839), TBP (ENSG00000112592)

Protein

Protein identifiers

TATA box-binding protein-like 2 — Q6SJ96 (reviewed: Q6SJ96)

Alternative names: TATA box-binding protein-related factor 3

All UniProt accessions (2): Q6SJ96, G3V454

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required in complex with TAF3 for the differentiation of myoblasts into myocytes. The complex replaces TFIID at specific promoters at an early stage in the differentiation process.

Subunit / interactions. Interacts with TAF3.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed in all tissues examined with highest levels in heart, lung, ovary, spleen and testes.

Similarity. Belongs to the TBP family.

RefSeq proteins (1): NP_950248* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000814	TBP	Family
IPR012295	TBP_dom_sf	Homologous_superfamily
IPR030491	TBP_CS	Conserved_site
IPR033710	TBP_eukaryotic	Family

Pfam: PF00352

UniProt features (5 total): compositionally biased region 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6SJ96-F1	70.12	0.52

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-1266738	Developmental Biology
R-HSA-9758941	Gastrulation

MSigDB gene sets: 13 (showing top): KEGG_HUNTINGTONS_DISEASE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_GENERAL_TRANSCRIPTION_INITIATION_FACTOR_ACTIVITY, CBX5_TARGET_GENES, MIR6715B_3P, GOMF_RNA_POLYMERASE_II_GENERAL_TRANSCRIPTION_INITIATION_FACTOR_ACTIVITY, ZSCAN4_TARGET_GENES, REACTOME_GERM_LAYER_FORMATION_AT_GASTRULATION, REACTOME_GASTRULATION, KEGG_BASAL_TRANSCRIPTION_FACTORS, chr14q22, TATAAA_TATA_01

GO Biological Process (2): DNA-templated transcription initiation (GO:0006352), transcription by RNA polymerase II (GO:0006366)

GO Molecular Function (2): DNA binding (GO:0003677), RNA polymerase II general transcription initiation factor activity (GO:0016251)

GO Cellular Component (3): female germ cell nucleus (GO:0001674), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gastrulation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
RNA biosynthetic process	1
nucleic acid binding	1
transcription by RNA polymerase II	1
general transcription initiation factor activity	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2131 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBPL2	TAF3	Q5VWG9	990
TBPL2	CDX4	O14627	906
TBPL2	RPS28	P25112	788
TBPL2	TERF1	P54274	774
TBPL2	RPS15	P11174	756
TBPL2	AGO3	Q9H9G7	670
TBPL2	GTF2B	Q00403	646
TBPL2	AGO2	Q9UKV8	638
TBPL2	TAF7L	Q5H9L4	628
TBPL2	AGO1	Q9UL18	625
TBPL2	TAF6	P49848	623
TBPL2	TAF4	O00268	608
TBPL2	BTAF1	O14981	571
TBPL2	ELAC2	Q9BQ52	564
TBPL2	TAF10	Q12962	542

IntAct

12 interactions, top by confidence:

A	B	Type	Score
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
NFKBIB	CHUK	psi-mi:“MI:0914”(association)	0.670
CCAR2	CEP170	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
SPATA25	TAF4	psi-mi:“MI:0914”(association)	0.530
TAF8	TAF4	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
LRRC46	GTPBP6	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): KPNA2 (Two-hybrid), MAP4K4 (Two-hybrid), DNAJB4 (Two-hybrid), KPNA2 (Reconstituted Complex), TBPL2 (Reconstituted Complex), TBPL2 (Affinity Capture-MS), TBPL2 (Affinity Capture-MS), TBPL2 (Affinity Capture-MS), TBPL2 (Affinity Capture-MS), NFYC (Co-localization), DNAJB5 (Reconstituted Complex), TBPL2 (Affinity Capture-Western), TBPL2 (Reconstituted Complex), TBPL2 (Affinity Capture-Western), TBPL2 (Co-fractionation)

ESM2 similar proteins: A2A5N8, A6H907, A6H909, B0JZV4, D3ZWK4, D4A4D7, E1BE02, E9Q0S6, O15021, O88866, P56931, P57058, Q0P4M4, Q16254, Q1JPY4, Q1LVK9, Q28DH2, Q3U1T9, Q5DTV4, Q5TKR9, Q5U5Z8, Q5UE94, Q5XK72, Q60592, Q68UT7, Q6A037, Q6DJS0, Q6IVY4, Q6P0Q8, Q6S7F2, Q6SJ94, Q6SJ95, Q6SJ96, Q7T2V3, Q7TNN8, Q7ZXG4, Q811L6, Q8BRB7, Q8BZ21, Q8CDK2

Diamond homologs: A0B5H8, A1RSQ1, A3MV36, A5UL47, A6H907, A6H909, A6URP5, A6UTF6, A6VIP7, A7UFC2, A9A840, B1Y949, B6YXI6, C4M7H7, C6A0R1, D4GZA2, D4H071, O13270, O17488, O27664, O29874, O43133, O45211, O52004, O52018, O58737, P13393, P17871, P20226, P20227, P26354, P26355, P26356, P26357, P27633, P28147, P28148, P29037, P32085, P32086

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TBPL2	“form complex”	TAF3/TRF3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1282 predictions. Top by Δscore:

Variant	Effect	Δscore
14:55424254:C:CC	acceptor_gain	1.0000
14:55437031:C:T	acceptor_gain	1.0000
14:55440390:CCTCA:C	donor_loss	1.0000
14:55440391:CTCA:C	donor_loss	1.0000
14:55440392:TCA:T	donor_loss	1.0000
14:55440394:AC:A	donor_loss	1.0000
14:55440395:C:CA	donor_loss	1.0000
14:55424152:CACTT:C	donor_loss	0.9900
14:55424153:ACTTA:A	donor_loss	0.9900
14:55424154:CTTA:C	donor_loss	0.9900
14:55424155:TTAC:T	donor_loss	0.9900
14:55424156:TACCT:T	donor_loss	0.9900
14:55424249:CGTAA:C	acceptor_gain	0.9900
14:55424262:A:C	acceptor_gain	0.9900
14:55424264:G:C	acceptor_gain	0.9900
14:55424813:C:CT	donor_gain	0.9900
14:55424813:CTA:C	donor_gain	0.9900
14:55424814:T:TT	donor_gain	0.9900
14:55433729:C:T	acceptor_gain	0.9900
14:55436773:A:AC	donor_gain	0.9900
14:55436774:C:CC	donor_gain	0.9900
14:55437031:C:CT	acceptor_gain	0.9900
14:55437032:A:T	acceptor_gain	0.9900
14:55438906:C:CT	acceptor_gain	0.9900
14:55438907:A:T	acceptor_gain	0.9900
14:55424213:CCATT:C	acceptor_gain	0.9800
14:55424214:CATTC:C	acceptor_gain	0.9800
14:55424251:TAA:T	acceptor_gain	0.9800
14:55424251:TAAC:T	acceptor_loss	0.9800
14:55424252:AA:A	acceptor_gain	0.9800

AlphaMissense

2449 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:55424176:C:A	G345V	1.000
14:55424176:C:T	G345E	1.000
14:55424184:A:C	F342L	1.000
14:55424184:A:T	F342L	1.000
14:55424186:A:G	F342L	1.000
14:55424227:A:G	L328P	1.000
14:55424235:A:C	F325L	1.000
14:55424235:A:T	F325L	1.000
14:55424237:A:G	F325L	1.000
14:55433657:C:A	G254V	1.000
14:55433657:C:T	G254E	1.000
14:55433665:A:C	F251L	1.000
14:55433665:A:T	F251L	1.000
14:55433667:A:G	F251L	1.000
14:55433672:A:G	L249P	1.000
14:55414401:A:G	L369P	0.999
14:55424185:A:C	F342C	0.999
14:55424186:A:T	F342I	0.999
14:55424191:A:G	L340P	0.999
14:55424222:A:C	Y330D	0.999
14:55424230:C:T	G327D	0.999
14:55424236:A:C	F325C	0.999
14:55428881:G:C	N294K	0.999
14:55428881:G:T	N294K	0.999
14:55433639:C:T	G260E	0.999
14:55433658:C:A	G254W	0.999
14:55433666:A:C	F251C	0.999
14:55433667:A:C	F251V	0.999
14:55433667:A:T	F251I	0.999
14:55433669:A:T	I250K	0.999

dbSNP variants (sampled 300 via entrez): RS1000249958 (14:55430758 C>G), RS1000443942 (14:55416865 G>A), RS1000577833 (14:55441119 T>C,G), RS1000671843 (14:55422117 G>C), RS1000862009 (14:55428189 G>A), RS1000991358 (14:55418130 T>A), RS1001050812 (14:55427730 A>G), RS1001278695 (14:55416998 A>T), RS1001323769 (14:55421716 A>G), RS1001345208 (14:55418424 C>T), RS1001436772 (14:55434553 C>T), RS1001526020 (14:55429151 G>A,T), RS1001650364 (14:55416170 G>T), RS1001753228 (14:55422634 T>C), RS1001778362 (14:55422790 T>C,G)

Disease associations

OMIM: gene MIM:608964 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004177_5	Pediatric bone mineral density (femoral neck)	1.000000e-08
GCST004178_12	Pediatric bone mineral density (hip)	4.000000e-06
GCST004179_6	Pediatric bone mineral content (femoral neck)	2.000000e-07
GCST004603_133	Platelet count	3.000000e-10
GCST004635_27	Testicular germ cell tumor	3.000000e-08
GCST008178_1	Early spontaneous preterm birth	5.000000e-06
GCST90002402_182	Platelet count	6.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0007702	hip bone mineral density
EFO:0007621	bone mineral content measurement
EFO:0004309	platelet count
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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