TFAP2B

Summary

TFAP2B (transcription factor AP-2 beta, HGNC:11743) is a protein-coding gene on chromosome 6p12.3, encoding Transcription factor AP-2-beta (Q92481). Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives.

Source: NCBI Gene 7021 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TFAP2B-related congenital heart disease spectrum disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 104
• Clinical variants (ClinVar): 190 total — 14 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 39
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_003221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11743
Approved symbol	TFAP2B
Name	transcription factor AP-2 beta
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	AP2-B, AP-2beta
Ensembl gene	ENSG00000008196
Ensembl biotype	protein_coding
OMIM	601601
Entrez	7021

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000344788, ENST00000393655, ENST00000489228

RefSeq mRNA: 1 — MANE Select: NM_003221 NM_003221

CCDS: CCDS4934

Canonical transcript exons

ENST00000393655 — 7 exons

Exon	Start	End
ENSE00000755942	50836061	50836280
ENSE00000756011	50840156	50840297
ENSE00001376604	50843092	50847619
ENSE00001662429	50837975	50838093
ENSE00003459906	50823407	50823865
ENSE00003790823	50828619	50828679
ENSE00003846010	50818871	50818972

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 97.38.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1926 / max 1079.5924, expressed in 297 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68211	2.4991	259
68210	0.6978	155
68209	0.5563	128
68216	0.4148	146
68207	0.3633	97
68212	0.1207	53
68204	0.1047	47
68206	0.0991	25
68218	0.0829	52
68217	0.0791	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	97.38	gold quality
cauda epididymis	UBERON:0004360	94.67	gold quality
oocyte	CL:0000023	92.66	gold quality
secondary oocyte	CL:0000655	91.35	gold quality
parotid gland	UBERON:0001831	88.79	gold quality
buccal mucosa cell	CL:0002336	87.00	gold quality
palpebral conjunctiva	UBERON:0001812	86.41	gold quality
renal medulla	UBERON:0000362	86.17	gold quality
epithelium of mammary gland	UBERON:0003244	83.62	gold quality
mammary duct	UBERON:0001765	83.46	gold quality
metanephros cortex	UBERON:0010533	80.22	gold quality
paraflocculus	UBERON:0005351	78.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.32	gold quality
frontal pole	UBERON:0002795	77.84	gold quality
mammary gland	UBERON:0001911	77.47	gold quality
thoracic mammary gland	UBERON:0005200	77.37	gold quality
middle frontal gyrus	UBERON:0002702	76.99	gold quality
upper leg skin	UBERON:0004262	76.76	gold quality
hair follicle	UBERON:0002073	76.23	gold quality
adult mammalian kidney	UBERON:0000082	76.00	gold quality
skin of hip	UBERON:0001554	75.89	gold quality
nipple	UBERON:0002030	75.20	gold quality
esophagus squamous epithelium	UBERON:0006920	74.98	gold quality
zone of skin	UBERON:0000014	74.76	gold quality
skin of abdomen	UBERON:0001416	74.37	gold quality
skin of leg	UBERON:0001511	73.85	gold quality
kidney	UBERON:0002113	73.55	gold quality
endometrium epithelium	UBERON:0004811	72.84	gold quality
esophagus mucosa	UBERON:0002469	72.69	gold quality
saliva-secreting gland	UBERON:0001044	72.63	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	2317.69
E-MTAB-6911	yes	1256.88
E-MTAB-10018	yes	457.03
E-HCAD-38	yes	277.97
E-GEOD-137537	yes	10.25
E-ANND-3	yes	7.36
E-MTAB-9388	yes	6.54

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ADIPOQ	Repression
APOE
BMP2	Unknown
BMP4	Unknown
CCL2	Activation
CD36	Activation
CRX	Repression
CRYAB	Activation
DRD1	Unknown
ERBB2	Unknown
FABP2
GNAS
IGFBP5	Repression
INS
IRAK2
IRS1
KISS1
LEP
MMP2	Activation
PLAUR
PNMT
PTGDS	Activation
RBL2
SOD2
TERT
TFAP2A
TNF	Activation
YEATS4

JASPAR motifs

Motif	Name	Family
MA0811.1	TFAP2B	AP-2
MA0811.2	TFAP2B	AP-2
MA0812.1	TFAP2B	AP-2
MA0812.2	TFAP2B	AP-2
MA0813.1	TFAP2B	AP-2

JASPAR matrix evidence (PMIDs): PMID:16420676

miRNA regulators (miRDB)

204 targeting TFAP2B, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4723-5P	99.97	68.70	2034

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Novel TFAP2B mutations causing Char syndrome have a dominant-negative effect and provide a genotype-phenotype correlation. (PMID:11505339)
• AP2 regulates human reduced folate carrier gene expression (PMID:12228234)
• no association between a transcription factor Activating Protein 2beta (AP-2beta) gene variant and schizophrenia (PMID:12270648)
• AP-2beta intron 2 genotype is associated with low levels of anxiety-related personality traits in women. (PMID:14673213)
• No association between the AP-2beta genotype and measures of dopamine receptor density, or CSF 5-HIAA concentrations. (PMID:15057523)
• AP-2beta expression was observed in the low-stage subtypes of renal cell carcinoma, and this transcription factor may be related to early carcinogenesis. (PMID:15245963)
• Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2 (PMID:15569994)
• No differences are observed in AP-2 beta genotype frequencies between 176 subjects with premenstrual dysphoric disorder (PMDD) and 91 healthy controls. (PMID:15722186)
• Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus. (PMID:15940393)
• TFAP2B may contribute to the pathogenesis of type 2 diabetes through regulation of adipocytokine gene expression, and that TFAP2B may be a promising target for treatment or prevention of this disease. (PMID:16373396)
• AP-2beta directly inhibits adiponectin gene expression by displacing NF-YA and binding to its promoter. (PMID:16954217)
• Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2beta genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance. (PMID:17123722)
• Investigators speculate on the possible role of TFAP2B gene on the duplicated segment in the three reported cases of partial trisomy. (PMID:17185054)
• TFAP2B was validated as direct target gene mediating the anti-apoptotic function of PAX3/FKHR (PMID:17525748)
• L-PGDS gene expression in TE671 cells was activated by USF1 through the aE-box within intron 4 and cooperatively by AP-2beta in the promoter in a cell-type-specific manner. (PMID:17574780)
• activating enhancer-binding protein-2beta (AP-2beta) as a novel transcription factor that specifically binds to and activates the hTERT promoter in human lung cancer cells. (PMID:17630431)
• a potential usefulness of AP-2beta polymorphisms in explaining or predicting central nervous diseases, drug effects and side effects. (PMID:18358611)
• Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus is reported. (PMID:18752453)
• Reduction of TFAP2B expression could have a protective effect against future risk of complications associated with decreased insulin sensitivity and central adiposity, such as type 2 diabetes and coronary heart disease. (PMID:19325541)
• TFAP2B, LYPLAL1 and MSRA are associated with adiposity and fat distribution. (PMID:19557161)
• The present study identifies TFAP2b as a suggestive candidate gene in alcohol dependence. (PMID:19778525)
• TFAP2B seems to regulate the expression of various adipokines in vivo (PMID:20019683)
• Loss of TFAP2B is associated with retinoblastoma. (PMID:20607706)
• A novel splice-junction in TFAP-2B gene might lead to hereditary patent ductus arteriosus in a Chinese family. (PMID:21215182)
• This study supports a role of the SLC6A4, DRD4 and TFAP2B genes in the temperament, including a gene-gene interaction between SLC6A4 and TFAP2B. It also provides evidence about an effect of the TFAP2B polymorphism in TFAP2B gene transcription. (PMID:21504541)
• TFAP2B mutation should be considered a risk factor for isolated PDA. However, the detailed genetic mechanism underlying nonsyndromic the PDA-causing TFAP2B mutation is yet to be elucidated. (PMID:21643846)
• central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B (PMID:21674055)
• It causes accumulation of neutral fats and causes insulin resistance through exaggerated glucose uptake independent of insulin and induces abnormal adipokine secretion, fat cell enlargement and insulin resistance. (PMID:21766608)
• The findings suggest the lack of involvement of known mutations of TFAP2B with syndromic or nonsyndromic CHDs in Mysore patients (PMID:22199100)
• Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction (PMID:22952648)
• genomic GATA4 and TFAP2B missense mutations may be associated with nonfamilial congenital heart disease with diverse clinical phenotypes in patients with congenital heart disease from southern China (PMID:22959235)
• The presence of the nine-repeat variant of the TFAP-2beta intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression. (PMID:23824473)
• The AP-2beta polymorphism significantly influenced cognitive performance, whereas the MAOA and COMT polymorphisms did not. (PMID:23881096)
• TFAP2B rs987237 and dietary protein/carbohydrate interacted to modify weight maintenance. (PMID:24081236)
• A haploinsufficiency effect of TFAP2B could be involved in familial isolated patent ductus arteriosus. (PMID:24507797)
• TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling. (PMID:24766673)
• The expression of TFAP-2beta mRNA in tissue of patients with endometrial carcinoma was higher than that of normal endometrium. The expression of TFAP-2beta mRNA in endometrial tissue of patients with metabolism syndrome was higher than that of lean ones. (PMID:26189251)
• results suggest that TFAP2B is playing a vital role in retaining retinoic acid responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. (PMID:26598443)
• Single nucleotide polymorphisms (SNP) in angiotensin II receptor, type 1 (AGTR1), transcription factor AP-2 beta (TFAP2B), and tumor necrosis factor receptor-associated factor 1 (TRAF1) have been reported to be associated with the incidence of PDA in preterm infants. (PMID:26615960)
• AP-2 beta and beta-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2 beta and the 1-9 Armadillo repeats of beta-catenin. (PMID:28277615)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfap2b	ENSDARG00000012667
mus_musculus	Tfap2b	ENSMUSG00000025927
rattus_norvegicus	Tfap2b	ENSRNOG00000011823
drosophila_melanogaster	TfAP-2	FBGN0261953
caenorhabditis_elegans		WBGENE00009202
caenorhabditis_elegans		WBGENE00009203
caenorhabditis_elegans		WBGENE00013383
caenorhabditis_elegans		WBGENE00019424

Paralogs (4): TFAP2D (ENSG00000008197), TFAP2C (ENSG00000087510), TFAP2E (ENSG00000116819), TFAP2A (ENSG00000137203)

Protein

Protein identifiers

Transcription factor AP-2-beta — Q92481 (reviewed: Q92481)

Alternative names: Activating enhancer-binding protein 2-beta

All UniProt accessions (2): Q92481, X6R4Y8

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5’-GCCNNNGGC-3’ and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia.

Subunit / interactions. Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with CITED4. Interacts with UBE2I. Interacts with KCTD1; this interaction represses transcription activation. Interacts with CITED2 (via C-terminus); the interaction stimulates TFAP2B-transcriptional activity.

Subcellular location. Nucleus.

Post-translational modifications. Sumoylated on Lys-21; which inhibits transcriptional activity.

Disease relevance. Char syndrome (CHAR) [MIM:169100] An autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies. The disease is caused by variants affecting the gene represented in this entry. Patent ductus arteriosus 2 (PDA2) [MIM:617035] A congenital heart defect characterized by the persistent opening of fetal ductus arteriosus that fails to close after birth. Fetal ductus arteriosus connects the pulmonary artery to the descending aorta, allowing unoxygenated blood to bypass the lung and flow to the placenta. Normally, the ductus occludes shortly after birth. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AP-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92481-1	1	yes
Q92481-2	2

RefSeq proteins (1): NP_003212* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004979	TF_AP2	Family
IPR008122	TF_AP2_beta	Family
IPR013854	TF_AP2_C	Domain

Pfam: PF03299

UniProt features (29 total): helix 9, sequence variant 6, compositionally biased region 3, region of interest 2, sequence conflict 2, strand 2, chain 1, turn 1, modified residue 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J0Q	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92481-F1	65.95	0.35

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 (2): 258, 21

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-8866904	Negative regulation of activity of TFAP2 (AP-2) family transcription factors
R-HSA-8866907	Activation of the TFAP2 (AP-2) family of transcription factors
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9834899	Specification of the neural plate border
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-9758941	Gastrulation

MSigDB gene sets: 412 (showing top): RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_METANEPHROS_DEVELOPMENT, JAEGER_METASTASIS_DN, GOBP_HINDLIMB_MORPHOGENESIS, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_ARTERY_DEVELOPMENT, TACAATC_MIR508

GO Biological Process (35): negative regulation of transcription by RNA polymerase II (GO:0000122), kidney development (GO:0001822), glucose metabolic process (GO:0006006), transcription by RNA polymerase II (GO:0006366), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), retina layer formation (GO:0010842), regulation of BMP signaling pathway (GO:0030510), forelimb morphogenesis (GO:0035136), hindlimb morphogenesis (GO:0035137), aorta morphogenesis (GO:0035909), regulation of cell population proliferation (GO:0042127), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of neuron apoptotic process (GO:0043525), skin development (GO:0043588), fat cell differentiation (GO:0045444), regulation of cell differentiation (GO:0045595), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), sympathetic nervous system development (GO:0048485), smooth muscle tissue development (GO:0048745), regulation of insulin secretion (GO:0050796), neuron apoptotic process (GO:0051402), distal tubule development (GO:0072017), collecting duct development (GO:0072044), metanephric nephron development (GO:0072210), ductus arteriosus closure (GO:0097070), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), sensory organ development (GO:0007423), gene expression (GO:0010467)

GO Molecular Function (13): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), protein heterodimerization activity (GO:0046982), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	3
SUMO E3 ligases SUMOylate target proteins	1
Gastrulation	1
RNA Polymerase II Transcription	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	3
transcription cis-regulatory region binding	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
animal organ development	2
regulation of cell population proliferation	2
limb morphogenesis	2
regulation of cellular process	2
regulation of neuron apoptotic process	2
neuron apoptotic process	2
cell differentiation	2
binding	2
protein dimerization activity	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
renal system development	1
hexose metabolic process	1
DNA-templated transcription	1
system development	1
positive regulation of cellular process	1
negative regulation of cellular process	1
response to chemical	1
neural retina development	1
anatomical structure formation involved in morphogenesis	1
retina morphogenesis in camera-type eye	1
BMP signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to growth factor stimulus	1
aorta development	1
artery morphogenesis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of apoptotic process	1
positive regulation of apoptotic process	1
regulation of developmental process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

1306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFAP2B	KCTD1	Q719H9	789
TFAP2B	GNPDA2	Q8TDQ7	663
TFAP2B	SEC16B	Q96JE7	658
TFAP2B	TMEM18	Q96B42	657
TFAP2B	KCTD15	Q96SI1	647
TFAP2B	MTCH2	Q9Y6C9	579
TFAP2B	CITED2	Q99967	574
TFAP2B	V9GXZ4	V9GXZ4	574
TFAP2B	FAIM2	Q9BWQ8	570
TFAP2B	LYPLAL1	Q5VWZ2	567
TFAP2B	TMEM160	Q9NX00	550
TFAP2B	MC4R	P32245	544
TFAP2B	YEATS4	O95619	542
TFAP2B	TNNI3K	Q59H18	529
TFAP2B	NEGR1	Q7Z3B1	527

IntAct

50 interactions, top by confidence:

A	B	Type	Score
YWHAG	TFAP2B	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	TFAP2B	psi-mi:“MI:0915”(physical association)	0.560
KAT5	TFAP2B	psi-mi:“MI:0915”(physical association)	0.560
LMO3	TFAP2B	psi-mi:“MI:0915”(physical association)	0.560
SMURF2	TFAP2B	psi-mi:“MI:0407”(direct interaction)	0.440
CITED2	TFAP2B	psi-mi:“MI:0915”(physical association)	0.400
CCL11	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
CCL27	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
CCL4L1	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
CCL5	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
CSF2	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL12B	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL15	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL17B	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL18	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL20	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL22	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370
IL3	TFAP2B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (24): CREBBP (Affinity Capture-Western), TFAP2B (Affinity Capture-Western), TFAP2B (Reconstituted Complex), TFAP2B (Affinity Capture-MS), TFAP2B (Reconstituted Complex), TFAP2B (Reconstituted Complex), TFAP2B (Reconstituted Complex), TFAP2B (Affinity Capture-MS), TFAP2B (Affinity Capture-Western), TFAP2A (Affinity Capture-MS), AK4 (Affinity Capture-MS), TFAP2B (Affinity Capture-MS), TFAP2D (Affinity Capture-MS), KLHL20 (Affinity Capture-MS), TFAP2B (Affinity Capture-MS)

ESM2 similar proteins: A1A4R9, A9CB91, O54835, O70436, P05549, P06435, P08651, P09286, P09414, P0C734, P11823, P11824, P13623, P17923, P19893, P21999, P30119, P34056, P42003, P58197, P70257, Q02780, Q09585, Q0ZME3, Q12857, Q14938, Q14EA6, Q15796, Q1HVD3, Q1W668, Q2T9K2, Q3KPS4, Q5R7C0, Q5RJ20, Q61312, Q61313, Q62432, Q6SW29, Q6SWP7, Q76HI7

Diamond homologs: A1A4R9, P05549, P34056, P58197, Q09585, Q2T9K2, Q5RJ20, Q61312, Q61313, Q6P0E7, Q6VUC0, Q6VUP9, Q76HI7, Q7Z6R9, Q91ZK0, Q92481, Q92754, Q9N0N3, G2HK15

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TFAP2B	“up-regulates quantity by expression”	CRYAB	“transcriptional regulation”
TFAP2B	“down-regulates quantity by repression”	ADIPOQ	“transcriptional regulation”
TFAP2B	“up-regulates quantity by stabilization”	TP53	binding
TFAP2B	“up-regulates quantity by expression”	PTGDS	“transcriptional regulation”
PRKD1	“down-regulates activity”	TFAP2B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Interleukin-10 signaling	5	43.2×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
antimicrobial humoral immune response mediated by antimicrobial peptide	5	26.1×	1e-04
cellular response to lipopolysaccharide	7	22.1×	4e-06
cell-cell signaling	7	15.7×	2e-05
immune response	10	15.2×	3e-07
inflammatory response	10	12.2×	1e-06
positive regulation of cell migration	5	10.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	12
Uncertain significance	91
Likely benign	41
Benign	23

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1176512	NM_003221.4(TFAP2B):c.276dup (p.Tyr93fs)	Pathogenic
1683496	NM_003221.4(TFAP2B):c.602-5_606del	Pathogenic
21359	NM_003221.4(TFAP2B):c.601+5G>A	Pathogenic
2284052	NM_003221.4(TFAP2B):c.601+1G>A	Pathogenic
243018	NM_003221.4(TFAP2B):c.541-2A>T	Pathogenic
243019	NM_003221.4(TFAP2B):c.439_442del (p.Pro147fs)	Pathogenic
3003446	NM_003221.4(TFAP2B):c.853C>T (p.Arg285Ter)	Pathogenic
3325591	NM_003221.4(TFAP2B):c.219dup (p.Tyr74fs)	Pathogenic
3390549	NM_003221.4(TFAP2B):c.328C>T (p.Gln110Ter)	Pathogenic
599040	NM_003221.4(TFAP2B):c.650del (p.Gly217fs)	Pathogenic
8039	NM_003221.4(TFAP2B):c.824C>A (p.Ala275Asp)	Pathogenic
8041	NM_003221.4(TFAP2B):c.706C>T (p.Arg236Cys)	Pathogenic
8042	NM_003221.4(TFAP2B):c.706C>A (p.Arg236Ser)	Pathogenic
8044	NM_003221.4(TFAP2B):c.218C>G (p.Pro73Arg)	Pathogenic
1326927	NM_003221.4(TFAP2B):c.707G>A (p.Arg236His)	Likely pathogenic
1344682	NM_003221.4(TFAP2B):c.3G>A (p.Met1Ile)	Likely pathogenic
1344683	NM_003221.4(TFAP2B):c.601+2T>A	Likely pathogenic
1344684	NM_003221.4(TFAP2B):c.827A>G (p.Lys276Arg)	Likely pathogenic
1344685	NM_003221.4(TFAP2B):c.1144C>T (p.Arg382Ter)	Likely pathogenic
2576106	NM_003221.4(TFAP2B):c.595A>T (p.Lys199Ter)	Likely pathogenic
2627564	NM_003221.4(TFAP2B):c.981C>A (p.Cys327Ter)	Likely pathogenic
3065996	NM_003221.4(TFAP2B):c.66C>G (p.Tyr22Ter)	Likely pathogenic
3253401	NM_003221.4(TFAP2B):c.899G>A (p.Arg300His)	Likely pathogenic
3910791	NM_003221.4(TFAP2B):c.620C>A (p.Ser207Ter)	Likely pathogenic
4532031	NM_003221.4(TFAP2B):c.767G>A (p.Arg256Gln)	Likely pathogenic
8040	NM_003221.4(TFAP2B):c.898C>T (p.Arg300Cys)	Likely pathogenic

SpliceAI

1341 predictions. Top by Δscore:

Variant	Effect	Δscore
6:50818970:GAG:G	donor_gain	1.0000
6:50818971:AGGT:A	donor_loss	1.0000
6:50818972:GGTG:G	donor_loss	1.0000
6:50818973:G:GG	donor_gain	1.0000
6:50818973:GTG:G	donor_loss	1.0000
6:50828618:GTCA:G	acceptor_gain	1.0000
6:50840298:G:GG	donor_gain	1.0000
6:50818974:T:G	donor_loss	0.9900
6:50828617:A:AG	acceptor_gain	0.9900
6:50828618:G:GG	acceptor_gain	0.9900
6:50828618:GT:G	acceptor_gain	0.9900
6:50828618:GTC:G	acceptor_gain	0.9900
6:50836059:A:AG	acceptor_gain	0.9900
6:50836060:G:GG	acceptor_gain	0.9900
6:50836060:GTTCC:G	acceptor_gain	0.9900
6:50843386:G:GT	donor_gain	0.9900
6:50843387:A:T	donor_gain	0.9900
6:50818971:AG:A	donor_gain	0.9800
6:50818972:GG:G	donor_gain	0.9800
6:50823402:CCCA:C	acceptor_loss	0.9800
6:50823403:CCAG:C	acceptor_loss	0.9800
6:50823405:AGGA:A	acceptor_loss	0.9800
6:50823406:G:GT	acceptor_gain	0.9800
6:50823861:TCCAG:T	donor_loss	0.9800
6:50823862:CCAG:C	donor_loss	0.9800
6:50823863:CAG:C	donor_loss	0.9800
6:50823864:AGGTA:A	donor_loss	0.9800
6:50823865:GGTAA:G	donor_loss	0.9800
6:50823866:G:T	donor_loss	0.9800
6:50823867:T:C	donor_loss	0.9800

AlphaMissense

2981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:50823530:T:C	Y69H	1.000
6:50823533:T:C	F70L	1.000
6:50823535:C:A	F70L	1.000
6:50823535:C:G	F70L	1.000
6:50836147:T:C	F230L	1.000
6:50836148:T:C	F230S	1.000
6:50836148:T:G	F230C	1.000
6:50836149:T:A	F230L	1.000
6:50836149:T:G	F230L	1.000
6:50836150:T:C	C231R	1.000
6:50836151:G:A	C231Y	1.000
6:50836152:C:G	C231W	1.000
6:50836157:T:A	V233D	1.000
6:50836159:C:T	P234S	1.000
6:50836160:C:A	P234Q	1.000
6:50836160:C:G	P234R	1.000
6:50836160:C:T	P234L	1.000
6:50836162:G:C	G235R	1.000
6:50836162:G:T	G235C	1.000
6:50836163:G:A	G235D	1.000
6:50836163:G:T	G235V	1.000
6:50836165:C:A	R236S	1.000
6:50836165:C:G	R236G	1.000
6:50836165:C:T	R236C	1.000
6:50836166:G:A	R236H	1.000
6:50836166:G:C	R236P	1.000
6:50836166:G:T	R236L	1.000
6:50836169:T:C	L237S	1.000
6:50836169:T:G	L237W	1.000
6:50836170:G:C	L237F	1.000

dbSNP variants (sampled 300 via entrez): RS1000092751 (6:50843730 T>A), RS1000211167 (6:50824873 A>C), RS1000272538 (6:50818748 G>A,C,T), RS1000363989 (6:50830458 A>G), RS1000820527 (6:50835459 C>T), RS1000871150 (6:50835649 A>C), RS1001009525 (6:50842729 A>G), RS1001039192 (6:50842382 G>A,C,T), RS1001084842 (6:50819180 T>C), RS1001216721 (6:50823267 G>C,T), RS1001346652 (6:50831992 T>C), RS1001425247 (6:50831770 A>G), RS1001483748 (6:50829432 T>A), RS1001503981 (6:50842444 A>G), RS1001598228 (6:50847050 G>T)

Disease associations

OMIM: gene MIM:601601 | disease phenotypes: MIM:169100, MIM:123100, MIM:617035

GenCC curated gene-disease

Disease	Classification	Inheritance
Char syndrome	Definitive	Autosomal dominant
patent ductus arteriosus 2	Strong	Autosomal dominant
familial patent arterial duct	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TFAP2B-related congenital heart disease spectrum disorder	Definitive	AD

Mondo (6): Char syndrome (MONDO:0008209), craniosynostosis (MONDO:0015469), chronic intestinal pseudoobstruction (MONDO:0017574), patent ductus arteriosus 2 (MONDO:0014878), TFAP2B-related congenital heart disease spectrum disorder (MONDO:1010098), (MONDO:0018758)

Orphanet (3): Char syndrome (Orphanet:46627), Craniosynostosis (Orphanet:1531), Chronic intestinal pseudoobstruction syndrome (Orphanet:2978)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000207	Triangular mouth
HP:0000232	Everted lower lip vermilion
HP:0000269	Prominent occiput
HP:0000272	Malar flattening
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000455	Broad nasal tip
HP:0000457	Depressed nasal ridge
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0001161	Hand polydactyly
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001629	Ventricular septal defect
HP:0001643	Patent ductus arteriosus
HP:0001770	Toe syndactyly
HP:0002360	Sleep disturbance
HP:0002553	Highly arched eyebrow
HP:0002558	Supernumerary nipple
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004218	Fifth finger symphalangism

GWAS associations

104 associations (top):

Study	Trait	p-value
GCST000428_3	Adiposity	2.000000e-11
GCST000830_29	Body mass index	3.000000e-20
GCST001007_3	Metabolic syndrome (bivariate traits)	1.000000e-07
GCST001240_2	Obesity (extreme)	3.000000e-08
GCST001610_13	Renal function-related traits (BUN)	2.000000e-07
GCST001953_1	Obesity	5.000000e-22
GCST001953_46	Obesity	3.000000e-19
GCST001953_52	Obesity	7.000000e-16
GCST001955_6	Body mass index	2.000000e-11
GCST002461_16	Body mass index	4.000000e-07
GCST002783_389	Body mass index	8.000000e-31
GCST002783_475	Body mass index	4.000000e-29
GCST002783_580	Body mass index	2.000000e-19
GCST002783_76	Body mass index	2.000000e-16
GCST003177_39	Childhood body mass index	2.000000e-12
GCST003830_36	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	1.000000e-07
GCST003997_19	Myopia	2.000000e-11
GCST004064_24	Waist-hip ratio	1.000000e-08
GCST004064_71	Waist-hip ratio	8.000000e-07
GCST004065_73	Waist circumference	1.000000e-10
GCST004065_74	Waist circumference	7.000000e-19
GCST004065_76	Waist circumference	1.000000e-11
GCST004066_35	Hip circumference	9.000000e-10
GCST004066_6	Hip circumference	7.000000e-11
GCST004066_87	Hip circumference	3.000000e-17
GCST004495_109	BMI (adjusted for smoking behaviour)	4.000000e-12
GCST004495_110	BMI (adjusted for smoking behaviour)	9.000000e-19
GCST004495_111	BMI (adjusted for smoking behaviour)	4.000000e-09
GCST004497_50	Body mass index (joint analysis main effects and smoking interaction)	4.000000e-21
GCST004497_51	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-13

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0000195	metabolic syndrome
EFO:0005921	FEV change measurement
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0006941	grip strength measurement
EFO:0004847	age at onset
EFO:0007041	obese body mass index status
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0009924	Drugs used in diabetes use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009963	bipolar I disorder
EFO:0005937	longitudinal BMI measurement
EFO:0008007	age at assessment
EFO:0008111	diet measurement
EFO:0004632	nevus count
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
C566815	Char syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs987237	TFAP2B		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, decreases methylation, affects cotreatment	8
trichostatin A	affects cotreatment, increases expression, affects expression, decreases reaction	4
Panobinostat	increases reaction, affects cotreatment, increases expression, affects expression	3
Nickel	decreases expression, decreases reaction, affects expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	affects expression, increases reaction, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
methylmercuric chloride	increases expression	1
ascorbate-2-phosphate	affects cotreatment, increases expression, affects binding	1
ethyl-p-hydroxybenzoate	increases expression	1
methylparaben	increases expression	1
manganese chloride	increases expression	1
sulindac sulfide	increases expression	1
butylparaben	increases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Chir 99021	affects binding, affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Cadmium	decreases expression	1
Hydrocortisone	affects cotreatment, 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_A7G7	SEES3-1V human TFAP2B, clone1	Embryonic stem cell	Male
CVCL_A7G8	SEES3-1V human TFAP2B, clone2	Embryonic stem cell	Male
CVCL_A7G9	SEES3-1V human TFAP2B, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00793247	PHASE2	COMPLETED	Efficacy Study of Prucalopride to Treat Chronic Intestinal Pseudo-Obstruction (CIP)
NCT04118699	PHASE2	UNKNOWN	Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial
NCT05724069	PHASE2	COMPLETED	Velusetrag for the Treatment of Chronic Intestinal Pseudo-Obstruction (CIPO).
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT00077831	Not specified	COMPLETED	Child and Infant Learning Project
NCT00106977	Not specified	COMPLETED	Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
NCT00367796	Not specified	COMPLETED	Genetic Analysis of Craniosynostosis, Philadelphia Type
NCT00769847	Not specified	WITHDRAWN	Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
NCT00773643	Not specified	COMPLETED	Osteogenic Profiling of Tissue From Children With Craniosynostosis
NCT01898650	Not specified	COMPLETED	MRI for Non-invasive Evaluation of Brain Stress
NCT02287805	Not specified	COMPLETED	Qualitative and Quantitative Study Which Aims to Determine the Specifics of the Announcement for the Diagnosis of Patients With Craniosynostosis and Their Parents to Better Support Them in Their Care
NCT02561728	Not specified	WITHDRAWN	Hanger Helmet Study
NCT03025763	Not specified	ACTIVE_NOT_RECRUITING	Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
NCT03231085	Not specified	COMPLETED	Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child
NCT04704284	Not specified	COMPLETED	Comparing MRI to CT on Pediatric Craniosynostosis.
NCT05911139	Not specified	ENROLLING_BY_INVITATION	Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
NCT06928727	Not specified	RECRUITING	Ocular Characteristics in Patients With Craniosynostosis
NCT02731183	Not specified	COMPLETED	Efficacy and Safety of Fecal Microbiota Transplantation for Chronic Intestinal Pseudo-obstruction
NCT04193735	Not specified	UNKNOWN	Pseudo-obstruction Assessment With MRI
NCT04506593	Not specified	RECRUITING	Indiana University Gastrointestinal Motility Diagnosis Registry
NCT06943417	Not specified	NOT_YET_RECRUITING	Safety and Efficacy of Endoscopic Full Thickness Biopsy in Patients With Chronic Intestinal Pseudo-obstruction