TCF23

Summary

TCF23 (transcription factor 23, HGNC:18602) is a protein-coding gene on chromosome 2p23.3, encoding Transcription factor 23 (Q7RTU1). Inhibits E-box-mediated binding and transactivation of bHLH factors.

The gene encodes a member of the basic helix-loop-helix transcription factor family. Studies of the orthologous gene in mouse have shown the encoded protein does not bind DNA but may negatively regulate other basic helix-loop-helix factors via the formation of a functionally inactive heterodimeric complex.

Source: NCBI Gene 150921 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 36 total
• Transcription factor: yes — 23 downstream targets (CollecTRI)
• MANE Select transcript: NM_175769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18602
Approved symbol	TCF23
Name	transcription factor 23
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	OUT, bHLHa24
Ensembl gene	ENSG00000163792
Ensembl biotype	protein_coding
OMIM	609635
Entrez	150921

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296096, ENST00000407815, ENST00000968520

RefSeq mRNA: 1 — MANE Select: NM_175769 NM_175769

CCDS: CCDS33163

Canonical transcript exons

ENST00000296096 — 3 exons

Exon	Start	End
ENSE00001078277	27150123	27150365
ENSE00001688488	27152688	27156974
ENSE00001835459	27149004	27149355

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 89.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2707 / max 140.2564, expressed in 23 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19327	0.1639	16
19328	0.0654	11
19326	0.0414	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	89.92	gold quality
left uterine tube	UBERON:0001303	89.70	gold quality
myometrium	UBERON:0001296	88.94	gold quality
right ovary	UBERON:0002118	82.68	gold quality
fallopian tube	UBERON:0003889	80.62	gold quality
ovary	UBERON:0000992	80.47	gold quality
left ovary	UBERON:0002119	79.37	gold quality
smooth muscle tissue	UBERON:0001135	76.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.22	gold quality
right uterine tube	UBERON:0001302	68.89	gold quality
endometrium	UBERON:0001295	62.15	gold quality
spleen	UBERON:0002106	62.15	gold quality
uterine cervix	UBERON:0000002	60.70	gold quality
endocervix	UBERON:0000458	60.67	gold quality
ectocervix	UBERON:0012249	58.95	gold quality
apex of heart	UBERON:0002098	56.86	gold quality
vagina	UBERON:0000996	56.35	gold quality
gall bladder	UBERON:0002110	55.85	gold quality
testis	UBERON:0000473	54.94	gold quality
muscle tissue	UBERON:0002385	53.58	gold quality
right testis	UBERON:0004534	52.28	gold quality
left testis	UBERON:0004533	52.24	gold quality
sural nerve	UBERON:0015488	51.58	gold quality
colonic epithelium	UBERON:0000397	49.17	gold quality
right coronary artery	UBERON:0001625	48.62	gold quality
skeletal muscle tissue	UBERON:0001134	46.93	gold quality
lymph node	UBERON:0000029	46.23	silver quality
duodenum	UBERON:0002114	45.82	gold quality
omental fat pad	UBERON:0010414	45.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.01	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.72
E-CURD-6	no	82.19
E-MTAB-4850	no	26.55
E-MTAB-6379	no	17.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

23 targets.

Target	Regulation
ALK
AMELX
CDKN1B
CIITA
CSF3
DBI
FGF21
HSPA4
HSPB1
IL5
INS
KDM6B
KRAS
MEN1
MMP1
MYOD1	Repression
ONECUT3
PARK7
PRDX1
SOD2
TCF3	Repression
TERT
TNF

Literature-anchored findings (GeneRIF, showing 2)

• Study of the orthologous gene in mouse shows the encoded protein does not bind DNA but may negatively regulate other basic helix-loop-helix factors via the formation of a functionally inactive heterodimeric complex. (PMID:10652346)
• Transcription factor 23 (Tcf23), a basic-helix-loop-helix transcription factor, is a new progesterone-induced target gene that requires SRC-2 for full induction. (PMID:24571987)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcf23	ENSDARG00000087381
mus_musculus	Tcf23	ENSMUSG00000006642
rattus_norvegicus	Tcf23	ENSRNOG00000074829
drosophila_melanogaster	twi	FBGN0003900
drosophila_melanogaster	HLH54F	FBGN0022740
drosophila_melanogaster	Hand	FBGN0032209
drosophila_melanogaster	CG33557	FBGN0053557
caenorhabditis_elegans		WBGENE00001953

Paralogs (13): HAND1 (ENSG00000113196), TCF21 (ENSG00000118526), TWIST1 (ENSG00000122691), TCF15 (ENSG00000125878), FERD3L (ENSG00000146618), HAND2 (ENSG00000164107), PTF1A (ENSG00000168267), MSC (ENSG00000178860), FIGLA (ENSG00000183733), BHLHA9 (ENSG00000205899), TWIST2 (ENSG00000233608), SCX (ENSG00000260428), TCF24 (ENSG00000261787)

Protein

Protein identifiers

Transcription factor 23 — Q7RTU1 (reviewed: Q7RTU1)

Alternative names: Class A basic helix-loop-helix protein 24

All UniProt accessions (1): Q7RTU1

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits E-box-mediated binding and transactivation of bHLH factors. Inhibitory effect is similar to that of ID proteins. Inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers. Lacks DNA binding activity. Seems to play a role in the inhibition of myogenesis.

Subunit / interactions. Forms inactive heterodimeric complexes with TCF3.

Subcellular location. Nucleus.

Tissue specificity. Expressed in liver, kidney and spleen.

Domain organisation. Both the bHLH region and the C-terminal portion are essential for inhibitory function.

RefSeq proteins (1): NP_786951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050283	E-box_TF_Regulators	Family

Pfam: PF00010

UniProt features (8 total): region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTU1-F1	62.54	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_DECIDUALIZATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_MATERNAL_PROCESS_INVOLVED_IN_FEMALE_PREGNANCY, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PLACENTA_DEVELOPMENT, GOBP_MATERNAL_PLACENTA_DEVELOPMENT, GOBP_MUSCLE_CELL_DIFFERENTIATION, GOCC_EUCHROMATIN, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), developmental process (GO:0032502), decidualization (GO:0046697), negative regulation of muscle cell differentiation (GO:0051148)

GO Molecular Function (6): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein dimerization activity (GO:0046983), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of gene expression	2
chromatin	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
animal organ development	1
muscle structure development	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
biological_process	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
muscle cell differentiation	1
negative regulation of cell differentiation	1
regulation of muscle cell differentiation	1
transcription cis-regulatory region binding	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
protein binding	1
DNA-binding transcription factor binding	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCF23	CIB4	A0PJX0	436
TCF23	RBKS	Q9H477	416
TCF23	CCDC116	Q8IYX3	412
TCF23	EFCAB5	A4FU69	410
TCF23	OLFM2	O95897	402
TCF23	BABAM2	Q9NXR7	388
TCF23	DEFB112	Q30KQ8	376
TCF23	PRRG3	Q9BZD7	360
TCF23	SNX17	Q15036	358
TCF23	ACCSL	Q4AC99	346
TCF23	GJD4	Q96KN9	345
TCF23	PATL2	C9JE40	337
TCF23	LRRC52	Q8N7C0	329
TCF23	FAM78A	Q5JUQ0	327
TCF23	RASL11A	Q6T310	324

IntAct

20 interactions, top by confidence:

A	B	Type	Score
EMD	TCF23	psi-mi:“MI:0915”(physical association)	0.560
TCF4	TCF23	psi-mi:“MI:0915”(physical association)	0.560
U2AF2	TCF23	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	TCF23	psi-mi:“MI:0915”(physical association)	0.560
TCF23	TCF12	psi-mi:“MI:0915”(physical association)	0.560
FIGLA	TCF23	psi-mi:“MI:0915”(physical association)	0.560
TCF23	CST4	psi-mi:“MI:0914”(association)	0.350
TCF23	TCF4	psi-mi:“MI:0915”(physical association)	0.000
TCF23	TCF12	psi-mi:“MI:0915”(physical association)	0.000
U2AF2	TCF23	psi-mi:“MI:0915”(physical association)	0.000
HNRNPK	TCF23	psi-mi:“MI:0915”(physical association)	0.000
FIGLA	TCF23	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): TCF23 (Two-hybrid), TCF23 (Two-hybrid), TCF23 (Two-hybrid), TCF23 (Two-hybrid), HNRNPK (Two-hybrid), FIGLA (Two-hybrid), TCF4 (Two-hybrid), TCF23 (Affinity Capture-MS), TCF23 (Affinity Capture-MS), TCF12 (Affinity Capture-MS), CST4 (Affinity Capture-MS), CST2 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), TCF4 (Affinity Capture-MS), TCF23 (Co-fractionation)

ESM2 similar proteins: A0A5F9ZHS7, A1YGK1, A2T7E6, A8MZG2, O08574, O43593, O60393, O75593, O88621, O95231, P0C1T1, P0CG20, P20428, P97609, Q04667, Q17QR5, Q2KIS6, Q2M1V0, Q2T9Q7, Q32LE6, Q497V6, Q5JUK2, Q5M844, Q5RJB0, Q5TGS1, Q61645, Q61657, Q6ZMY3, Q6ZN32, Q6ZNG2, Q7RTU1, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8N1L9, Q8N7G0, Q8N944, Q8N9Y4

Diamond homologs: A8E5T6, B6VQA1, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P48985, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70661, P79765, P79782, P97831, P97832, Q02575, Q02576, Q02577, Q0VCE2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

552 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27150362:CAAGG:C	donor_loss	1.0000
2:27150363:AAGG:A	donor_loss	1.0000
2:27150364:AGGTA:A	donor_loss	1.0000
2:27150366:GTAA:G	donor_loss	1.0000
2:27149351:GCAGG:G	donor_gain	0.9900
2:27149354:GG:G	donor_gain	0.9900
2:27149355:GG:G	donor_gain	0.9900
2:27149356:G:GG	donor_gain	0.9900
2:27150121:A:AG	acceptor_gain	0.9900
2:27150122:G:GG	acceptor_gain	0.9900
2:27150122:GA:G	acceptor_gain	0.9900
2:27150122:GAGC:G	acceptor_gain	0.9900
2:27150361:TCAAG:T	donor_gain	0.9900
2:27150362:CAAG:C	donor_gain	0.9900
2:27150363:AAG:A	donor_gain	0.9900
2:27150364:AG:A	donor_gain	0.9900
2:27150365:GG:G	donor_gain	0.9900
2:27150366:G:GG	donor_gain	0.9900
2:27151017:T:G	donor_gain	0.9900
2:27152796:TCCC:T	donor_gain	0.9900
2:27149353:AGGG:A	donor_loss	0.9800
2:27149355:GGTA:G	donor_loss	0.9800
2:27149356:GT:G	donor_loss	0.9800
2:27149357:T:G	donor_loss	0.9800
2:27150121:AGAGC:A	acceptor_gain	0.9800
2:27150122:GAGCG:G	acceptor_gain	0.9800
2:27151045:GGT:G	donor_gain	0.9800
2:27152687:GAA:G	acceptor_gain	0.9800
2:27150122:G:C	acceptor_gain	0.9700
2:27152687:GAAGT:G	acceptor_gain	0.9700

AlphaMissense

1359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27150242:G:C	K114N	0.993
2:27150242:G:T	K114N	0.993
2:27152691:T:A	W157R	0.991
2:27152691:T:C	W157R	0.991
2:27152693:G:C	W157C	0.991
2:27152693:G:T	W157C	0.991
2:27150186:T:C	F96L	0.987
2:27150188:C:A	F96L	0.987
2:27150188:C:G	F96L	0.987
2:27150196:T:C	L99S	0.986
2:27150262:C:A	A121D	0.985
2:27150238:C:T	S113F	0.984
2:27150240:A:G	K114E	0.984
2:27150283:T:C	L128P	0.984
2:27150187:T:C	F96S	0.983
2:27150247:A:T	D116V	0.981
2:27150155:G:C	E85D	0.980
2:27150155:G:T	E85D	0.980
2:27150233:G:C	K111N	0.977
2:27150233:G:T	K111N	0.977
2:27150274:T:A	I125K	0.977
2:27150241:A:T	K114M	0.975
2:27150183:G:C	A95P	0.974
2:27150238:C:A	S113Y	0.974
2:27150154:A:T	E85V	0.970
2:27150187:T:G	F96C	0.970
2:27150365:G:C	K155N	0.970
2:27150365:G:T	K155N	0.970
2:27150253:T:A	L118Q	0.964
2:27150208:T:A	L103Q	0.963

dbSNP variants (sampled 300 via entrez): RS1000390599 (2:27155206 G>A,T), RS1000988473 (2:27153233 G>A), RS1001266350 (2:27153303 A>G), RS1001321785 (2:27151500 A>C), RS1001796715 (2:27154273 C>T), RS1002523321 (2:27156629 G>A,T), RS1002772132 (2:27152985 C>A,T), RS1002946243 (2:27150221 G>A), RS1003273406 (2:27148648 C>T), RS1003327529 (2:27148973 G>A), RS1003680931 (2:27151149 A>G), RS1003788070 (2:27154895 T>C), RS1003869497 (2:27149026 A>T), RS1004025318 (2:27156850 C>A,G,T), RS1004076330 (2:27157243 C>G)

Disease associations

OMIM: gene MIM:609635 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST010697_14	Cortical surface area (min-P)	2.000000e-09
GCST010698_75	Subcortical volume (min-P)	2.000000e-13
GCST010699_41	Brain morphology (min-P)	2.000000e-08
GCST010700_38	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_56	Cortical surface area (MOSTest)	4.000000e-16
GCST010702_20	Subcortical volume (MOSTest)	2.000000e-64
GCST010703_76	Brain morphology (MOSTest)	1.000000e-16
GCST012020_244	Serum metabolite levels	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(2-butoxyethyl) phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7D4	SEES3-1V human TCF23, clone1	Embryonic stem cell	Male
CVCL_A7D5	SEES3-1V human TCF23, clone2	Embryonic stem cell	Male
CVCL_A7D6	SEES3-1V human TCF23, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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