ZFPM2

Summary

ZFPM2 (zinc finger protein, FOG family member 2, HGNC:16700) is a protein-coding gene on chromosome 8q23, encoding Zinc finger protein ZFPM2 (Q8WW38). Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.

The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence.

Source: NCBI Gene 23414 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tetralogy of fallot (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 149
• Clinical variants (ClinVar): 315 total — 4 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 84
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_012082

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16700
Approved symbol	ZFPM2
Name	zinc finger protein, FOG family member 2
Location	8q23
Locus type	gene with protein product
Status	Approved
Aliases	PRDM19, FOG2, hFOG-2, ZNF89B
Ensembl gene	ENSG00000169946
Ensembl biotype	protein_coding
OMIM	603693
Entrez	23414

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000407775, ENST00000511341, ENST00000517361, ENST00000518180, ENST00000520027, ENST00000520492, ENST00000521923, ENST00000522160, ENST00000522296, ENST00000524235, ENST00000941376

RefSeq mRNA: 3 — MANE Select: NM_012082 NM_001362836, NM_001362837, NM_012082

CCDS: CCDS47908, CCDS94333

Canonical transcript exons

ENST00000407775 — 8 exons

Exon	Start	End
ENSE00001549408	105318438	105318981
ENSE00002135760	105801047	105804539
ENSE00003476852	105634246	105634357
ENSE00003531617	105419144	105419302
ENSE00003568162	105561363	105561481
ENSE00003591321	105788718	105788924
ENSE00003630571	105798724	105798948
ENSE00003663608	105444280	105444381

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 93.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8705 / max 707.9248, expressed in 1103 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90190	9.0653	1030
90191	2.4462	688
90189	0.4540	217
90193	0.4456	197
90195	0.3623	144
90188	0.3002	158
90194	0.2631	122
90197	0.1921	78
90187	0.1621	82
90192	0.0921	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.87	gold quality
germinal epithelium of ovary	UBERON:0001304	93.81	gold quality
biceps brachii	UBERON:0001507	93.64	gold quality
cartilage tissue	UBERON:0002418	92.40	gold quality
vastus lateralis	UBERON:0001379	92.36	gold quality
gluteal muscle	UBERON:0002000	92.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.80	gold quality
triceps brachii	UBERON:0001509	91.45	gold quality
quadriceps femoris	UBERON:0001377	91.39	gold quality
pons	UBERON:0000988	91.06	gold quality
parietal pleura	UBERON:0002400	90.61	gold quality
left ventricle myocardium	UBERON:0006566	90.60	gold quality
myocardium	UBERON:0002349	90.54	gold quality
skeletal muscle tissue	UBERON:0001134	90.52	gold quality
deltoid	UBERON:0001476	90.44	gold quality
cortical plate	UBERON:0005343	90.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.25	gold quality
muscle tissue	UBERON:0002385	90.07	gold quality
cerebellum	UBERON:0002037	89.41	gold quality
endothelial cell	CL:0000115	89.29	silver quality
ovary	UBERON:0000992	89.20	gold quality
sural nerve	UBERON:0015488	89.11	gold quality
left ovary	UBERON:0002119	88.64	gold quality
heart right ventricle	UBERON:0002080	88.62	gold quality
cerebellar cortex	UBERON:0002129	88.47	gold quality
cerebellar hemisphere	UBERON:0002245	88.35	gold quality
blood vessel layer	UBERON:0004797	87.90	gold quality
right ovary	UBERON:0002118	87.45	gold quality
cauda epididymis	UBERON:0004360	87.34	gold quality
cerebellar vermis	UBERON:0004720	87.17	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	1743.33
E-GEOD-131882	yes	1364.43
E-HCAD-35	yes	69.76
E-HCAD-25	yes	16.61
E-ANND-3	yes	8.18

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ADAM2
ATP2A2	Repression
CISH
DCN
DLD
GADD45G
GATA4
KCND2	Unknown
KL
LHX9
MAP3K14
NOTCH1
NPPA
SOX9	Unknown

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 28)

• FOG-2 has specific role in fetal ovaries counteracting transactivation of mullerian-inhibiting substance gene by GATA-4. Important role for FOG-2 and GATA transcription factors in developing ovary. (PMID:12606418)
• AML1-FOG2 and FOG2-AML1 are expressed in myelodysplastic syndrome; results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of AML1 and GATA developmental programs in the disease pathogenesis (PMID:15705784)
• FOG-2 affects not only cardiac development but also gonadal function and its preservation (PMID:17309641)
• sequence variation in diaphragmatic hernia (PMID:17568391)
• SERCA2 is an important target of FOG-2 and that increased FOG-2 expression may contribute to a decline in cardiac function in end-stage heart failure by impaired T3 signaling (PMID:18658259)
• Comparative analyses identify USH and its human homolog, FOG2, as the targets of fly miR-8 and human miR-200, respectively; USH/FOG2 inhibits PI3K activity, suppressing cell growth in both flies and humans. (PMID:20005803)
• These results implicate FOG1 and 2 and CTBPs as partners of GATA proteins in the control of adipocyte proliferation and differentiation. (PMID:20705609)
• New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle (PMID:20807224)
• Variants of the ZFPM2/FOG2 gene might be a common cause of Double outlet right ventricle. (PMID:21919901)
• association of the ZFPM2 SNP, rs12678719, with antipsychotic-induced parkinsonism (PMID:21947317)
• Sex Cord Stromal Tumors in childhood exhibited an embryonal gonadal phenotype, expressing a FOG-2/GATA-4 pattern in keeping with embryonal gonads. (PMID:23029311)
• FOG1, FOG2 and GATA-6 modulate the transcriptional up-regulation of HAMP in hepatocytes during inflammation. (PMID:24179092)
• our results provide strong evidence regarding the susceptibility of the ZFPM2 gene to the development of non-syndromic TOF/DORV. (PMID:24469719)
• Whole exome sequencing identified independent missense mutations in FOG2 in two patients with 46,XY gonadal dysgenesis. (PMID:24549039)
• Isolated congenital diaphragmatic hernia was the predominant phenotype observed in our ZFPM2 mutation patients. (PMID:24702427)
• Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes. (PMID:24743694)
• Findings indicate that zinc finger protein, multitype 2 protein (ZFPM2) plays a role in diaphragm and cardiovascular development. (PMID:24769157)
• screened a larger CTD population, which comprised 145 tetralogy of Fallot (TOF), 37 double-outlet ventricle outflow (DORV), and 18 transposition of the great artery (TGA), to investigate exon mutations as well as copy number variations in ZFPM2/FOG2 (PMID:25025186)
• ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity. The balancing selection acting on ZFPM2 may relate to its roles in multiple organ development or associated disease etiology. (PMID:26207917)
• Aberrant methylation status at the promoter CpG island shore of ZFPM2 gene may be associated with its gene transcription regulation in the tetralogy of fallot patients (PMID:26959486)
• Genetic Analysis of Venous Thromboembolism in UK Biobank Identifies the ZFPM2 Locus and Implicates Obesity as a Causal Risk Factor. (PMID:28373160)
• when ZFPM2R698Q was co-transfected with GATA4, BNP promoter activity increased significantly, whereas co-transfection with ZFPM2R736L and GATA4 did not significantly increase BNP promoter activity. This suggests that the R698Q mutation may affect the ability of ZFPM2 to bind GATA4. (PMID:29018978)
• The single nucleotide polymorphisms (SNPs) of NKX2.5, GATA4, and TBX5 are highly associated with congenital heart diseases in the Chinese population, but not significant in the SNPs of FOG2. (PMID:29972125)
• LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. (PMID:31919993)
• Analysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development. (PMID:31962012)
• EphA3 promotes the proliferation of NPC cells through negatively regulating the ability of FOG2. (PMID:32633364)
• Long noncoding RNA CCDC26 as a modulator of transcriptional switching between fetal and embryonic globins. (PMID:33340546)
• A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network. (PMID:38189150)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfpm2a	ENSDARG00000040123
mus_musculus	Zfpm2	ENSMUSG00000022306
rattus_norvegicus	Zfpm2	ENSRNOG00000004109
drosophila_melanogaster	ush	FBGN0003963

Paralogs (1): ZFPM1 (ENSG00000179588)

Protein

Protein identifiers

Zinc finger protein ZFPM2 — Q8WW38 (reviewed: Q8WW38)

Alternative names: Friend of GATA protein 2, Zinc finger protein 89B, Zinc finger protein multitype 2

All UniProt accessions (3): Q8WW38, E5RJX0, E7ET52

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulating expression of SRY. Probably acts a corepressor of NR2F2.

Subunit / interactions. Interacts with the N-terminal zinc-finger of GATA4, GATA5 and probably GATA6. Interacts with retinoid nuclear receptor RXRA when ligand bound. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity. Able to bind GATA1 in vitro. Interacts with NR2F2 and NR2F6. Interacts with ATOH8; mediates indirect interaction with GATA4.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed at low level.

Post-translational modifications. Sumoylation reduces transcriptional repression activity.

Disease relevance. Tetralogy of Fallot (TOF) [MIM:187500] A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. The disease may be caused by variants affecting the gene represented in this entry. Diaphragmatic hernia 3 (DIH3) [MIM:610187] A form of congenital diaphragmatic hernia, a posterolateral defect of the diaphragm, generally located on the left side, that permits the herniation of abdominal viscera into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. The disease is caused by variants affecting the gene represented in this entry. 46,XY sex reversal 9 (SRXY9) [MIM:616067] A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females or have ambiguous external genitalia. The disease is caused by variants affecting the gene represented in this entry. Conotruncal heart malformations (CTHM) [MIM:217095] A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CCHC FOG-type zinc fingers 1, 2, 3 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers.

Miscellaneous. Sequence incomplete.

Similarity. Belongs to the FOG (Friend of GATA) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WW38-1	1	yes
Q8WW38-2	2

RefSeq proteins (3): NP_001349765, NP_001349766, NP_036214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR034731	Znf_CCHC_FOG	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039746	FOG	Family
IPR049361	ZFPM1/2_PR	Domain
IPR059121	CCHC_ZFPM2-like	Domain

Pfam: PF21182, PF25445

UniProt features (65 total): binding site 20, sequence variant 9, zinc finger region 8, compositionally biased region 8, region of interest 5, cross-link 5, modified residue 4, splice variant 2, sequence conflict 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WW38-F1	51.93	0.06

Functional residue map

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

Ligand- & substrate-binding residues (20): 252; 255; 268; 273; 550; 553; 566; 571; 689; 692; 705; 710 …

Post-translational modifications (9): 532, 581, 904, 1014, 324, 444, 471, 915, 955

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9690406	Transcriptional regulation of testis differentiation
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 539 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, TGCACTT_MIR519C_MIR519B_MIR519A

GO Biological Process (23): negative regulation of transcription by RNA polymerase II (GO:0000122), vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), outflow tract septum morphogenesis (GO:0003148), right ventricular cardiac muscle tissue morphogenesis (GO:0003221), gonadal mesoderm development (GO:0007506), heart development (GO:0007507), cell differentiation (GO:0030154), lung development (GO:0030324), fat cell differentiation (GO:0045444), negative regulation of fat cell differentiation (GO:0045599), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic organ development (GO:0048568), positive regulation of cardiac muscle cell proliferation (GO:0060045), ventricular septum morphogenesis (GO:0060412), positive regulation of male gonad development (GO:2000020), negative regulation of female gonad development (GO:2000195), outflow tract morphogenesis (GO:0003151), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), cardiac muscle tissue development (GO:0048738), cardiac muscle tissue morphogenesis (GO:0055008)

GO Molecular Function (7): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
animal organ development	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
cell differentiation	2
cardiac septum morphogenesis	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
transcription coregulator activity	2
blood vessel morphogenesis	1
chordate embryonic development	1
outflow tract morphogenesis	1
cardiac right ventricle morphogenesis	1
ventricular cardiac muscle tissue morphogenesis	1
developmental process involved in reproduction	1
mesoderm development	1
gonad development	1
mesenchyme development	1
circulatory system development	1
cellular developmental process	1
respiratory tube development	1
respiratory system development	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
embryo development	1
positive regulation of cell population proliferation	1
positive regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
regulation of cardiac muscle cell proliferation	1
ventricular septum development	1
male gonad development	1
positive regulation of gonad development	1
regulation of male gonad development	1
female gonad development	1
negative regulation of gonad development	1
regulation of female gonad development	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFPM2	GATA4	P43694	997
ZFPM2	PIK3R1	P27986	961
ZFPM2	GATA6	P78327	876
ZFPM2	NR2F2	P24468	787
ZFPM2	GATA1	P15976	766
ZFPM2	NKX2-5	P52952	731
ZFPM2	CTBP2	P56545	719
ZFPM2	TBX20	Q9UMR3	700
ZFPM2	TBX5	Q99593	673
ZFPM2	HAND2	P61296	656
ZFPM2	MEF2C	Q06413	650
ZFPM2	MECOM	Q03112	640
ZFPM2	AMH	P03971	627
ZFPM2	GATA5	Q9BWX5	627
ZFPM2	ICAM2	P13598	567

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PRPF3	ZFPM2	psi-mi:“MI:0915”(physical association)	0.560
ZFPM2	DMWD	psi-mi:“MI:0915”(physical association)	0.560
ZFPM2	GFAP	psi-mi:“MI:0915”(physical association)	0.560
LMNA	ZFPM2	psi-mi:“MI:0915”(physical association)	0.560
ZFPM2	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ZFPM2	FMR1	psi-mi:“MI:0915”(physical association)	0.370
ZFPM2	STAT3	psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RBBP4	PHF20L1	psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
GATA1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
GATA2	BCL9	psi-mi:“MI:2364”(proximity)	0.270
GATA3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
PRPF3	ZFPM2	psi-mi:“MI:0915”(physical association)	0.000
UBQLN4	ZFPM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (55): ZFPM2 (Two-hybrid), ZFPM2 (Two-hybrid), ZFPM2 (Affinity Capture-MS), ZFPM2 (Affinity Capture-MS), ZFPM2 (Affinity Capture-MS), ZFPM2 (Two-hybrid), ZFPM2 (Two-hybrid), ZFPM2 (Two-hybrid), ZFPM2 (Affinity Capture-Western), ZFPM2 (Reconstituted Complex), ZFPM2 (Two-hybrid), ZFPM2 (Affinity Capture-MS), GATA1 (Reconstituted Complex), ZFPM2 (Reconstituted Complex), ZFPM2 (Two-hybrid)

ESM2 similar proteins: A0A0R4IYX6, A0A1D5NVS8, A0A1L8H0H2, A0AVK6, A5GFT6, A7XYH5, A7XYJ6, B7ZS37, B8A5Y1, D4A666, E1B7L7, E1BKK0, E1BLP6, F1LMN3, F6YVB9, F8VPJ6, Q12766, Q13029, Q14B70, Q2HNT1, Q2HNT2, Q2KHR2, Q4V9H5, Q58FA4, Q5DTH5, Q5ZIE8, Q5ZIX8, Q5ZJ69, Q5ZM88, Q63679, Q63755, Q68FE9, Q69ZF8, Q6DRC5, Q6P4F7, Q6PCM1, Q6ZSZ6, Q76L83, Q80Y19, Q8BHZ4

Diamond homologs: A2A884, E9PZZ1, J9VE33, O35615, P15822, P31629, P39770, P39806, P60622, Q00900, Q02032, Q03172, Q3UHF7, Q5JPB2, Q5T1R4, Q6DCW1, Q8CCH7, Q8IX07, Q8WUU4, Q8WW38, Q9BXA9, Q9ER74, Q9H165, Q9H4Q3, Q9I9K0, Q9NSC2, Q9QYE3, Q00453, Q8BI69, Q9UJQ4, Q5SVQ8, Q811F1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZFPM2	“down-regulates activity”	GATA4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell population proliferation	6	11.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	8
Uncertain significance	179
Likely benign	60
Benign	27

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1451277	NM_012082.4(ZFPM2):c.931C>T (p.Arg311Ter)	Pathogenic
156583	NM_012082.4(ZFPM2):c.1206T>A (p.Ser402Arg)	Pathogenic
1706571	NM_012082.4(ZFPM2):c.349C>T (p.Arg117Ter)	Pathogenic
39517	NM_012082.4(ZFPM2):c.681T>G (p.Ile227Met)	Pathogenic
1299632	NM_012082.4(ZFPM2):c.192T>G (p.Cys64Trp)	Likely pathogenic
2572676	NM_012082.4(ZFPM2):c.1579C>T (p.Arg527Ter)	Likely pathogenic
3033583	NM_012082.4(ZFPM2):c.10C>T (p.Arg4Ter)	Likely pathogenic
3067633	NM_012082.4(ZFPM2):c.1480_1493del (p.Val494fs)	Likely pathogenic
3235947	GRCh38/hg38 8q23.1(chr8:105628485-105634938)	Likely pathogenic
3356187	NM_012082.4(ZFPM2):c.302-2A>C	Likely pathogenic
4280046	NM_012082.4(ZFPM2):c.964+1G>C	Likely pathogenic
503850	NM_012082.4(ZFPM2):c.1400dup (p.Tyr467Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

7659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:105634291:T:A	W156R	1.000
8:105634291:T:C	W156R	1.000
8:105798730:T:A	I249K	1.000
8:105798732:T:C	F250L	1.000
8:105798733:T:C	F250S	1.000
8:105798733:T:G	F250C	1.000
8:105798734:C:A	F250L	1.000
8:105798734:C:G	F250L	1.000
8:105798738:T:A	C252S	1.000
8:105798738:T:C	C252R	1.000
8:105798739:G:A	C252Y	1.000
8:105798739:G:C	C252S	1.000
8:105798739:G:T	C252F	1.000
8:105798740:C:G	C252W	1.000
8:105798747:T:A	C255S	1.000
8:105798747:T:C	C255R	1.000
8:105798748:G:A	C255Y	1.000
8:105798748:G:C	C255S	1.000
8:105798748:G:T	C255F	1.000
8:105798749:T:G	C255W	1.000
8:105798754:T:A	I257N	1.000
8:105798754:T:G	I257S	1.000
8:105798756:T:A	W258R	1.000
8:105798756:T:C	W258R	1.000
8:105798759:T:G	Y259D	1.000
8:105798765:A:C	S261R	1.000
8:105798767:T:A	S261R	1.000
8:105798767:T:G	S261R	1.000
8:105798774:A:G	N264D	1.000
8:105798776:T:A	N264K	1.000

dbSNP variants (sampled 300 via entrez): RS1000011387 (8:105646692 A>G), RS1000032214 (8:105332111 T>C), RS1000046072 (8:105376219 T>C), RS1000055167 (8:105601095 G>C), RS1000057322 (8:105435004 A>C), RS1000062609 (8:105652266 C>A), RS1000080938 (8:105694332 A>C,G), RS1000090980 (8:105564412 T>G), RS1000098429 (8:105605718 A>G), RS1000100986 (8:105519269 A>T), RS1000104665 (8:105369377 T>A,G), RS1000142247 (8:105395335 G>A,C), RS1000155683 (8:105369615 A>G), RS1000158504 (8:105565778 CAAGT>C), RS1000164662 (8:105744402 T>C)

Disease associations

OMIM: gene MIM:603693 | disease phenotypes: MIM:616067, MIM:187500, MIM:610187, MIM:612965

GenCC curated gene-disease

Disease	Classification	Inheritance
tetralogy of fallot	Strong	Autosomal dominant
diaphragmatic hernia 3	Strong	Autosomal dominant
46,XY sex reversal 9	Strong	Autosomal dominant
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant

Mondo (6): 46,XY sex reversal 9 (MONDO:0014480), tetralogy of fallot (MONDO:0008542), diaphragmatic hernia 3 (MONDO:0012431), 46,XY sex reversal 3 (MONDO:0013066), double outlet right ventricle (MONDO:0018089), 46,XY partial gonadal dysgenesis (MONDO:0016674)

Orphanet (4): 46,XY partial gonadal dysgenesis (Orphanet:251510), Tetralogy of Fallot (Orphanet:3303), Congenital diaphragmatic hernia (Orphanet:2140), Double outlet right ventricle (Orphanet:3426)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000063	Fused labia minora
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000268	Dolichocephaly
HP:0000337	Broad forehead
HP:0000403	Recurrent otitis media
HP:0000520	Proptosis
HP:0000729	Autistic behavior
HP:0000771	Gynecomastia
HP:0000776	Congenital diaphragmatic hernia
HP:0000786	Primary amenorrhea
HP:0000812	Abnormal internal genitalia
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000846	Adrenal insufficiency

GWAS associations

149 associations (top):

Study	Trait	p-value
GCST001099_2	Sudden cardiac arrest	1.000000e-06
GCST001155_2	Vascular endothelial growth factor levels	5.000000e-23
GCST001337_23	Platelet count	4.000000e-17
GCST001493_1	Glaucoma (primary open-angle)	9.000000e-10
GCST001877_72	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-07
GCST002097_44	Coronary artery calcification	6.000000e-06
GCST002198_13	Tuberculosis	3.000000e-06
GCST002808_1	Venous thromboembolism	5.000000e-07
GCST003383_8	Platelet count	3.000000e-08
GCST003403_5	Vascular endothelial growth factor levels	4.000000e-55
GCST004256_7	Venous thromboembolism	5.000000e-10
GCST004599_65	Mean platelet volume	1.000000e-34
GCST004603_76	Platelet count	1.000000e-67
GCST004607_168	Plateletcrit	7.000000e-40
GCST004616_196	Platelet distribution width	2.000000e-52
GCST004618_14	White blood cell count (basophil)	2.000000e-09
GCST004776_43	Systolic blood pressure	7.000000e-09
GCST004776_93	Systolic blood pressure	5.000000e-07
GCST005194_225	Coronary artery disease	1.000000e-08
GCST005195_78	Coronary artery disease	2.000000e-08
GCST005991_92	Platelet count	2.000000e-11
GCST006575_53	Takayasu arteritis	2.000000e-06
GCST007045_32	PR interval	4.000000e-10
GCST007627_4	Impulsivity (attentional)	2.000000e-06
GCST007656_3	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-11
GCST008362_180	Birth weight	6.000000e-13
GCST009030_9	Venous thromboembolism	7.000000e-14
GCST009097_4	Venous thromboembolism	4.000000e-19
GCST009243_3	Cytokine levels	1.000000e-07
GCST009244_9	Cytokine network levels (multivariate analysis)	5.000000e-08

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0004309	platelet count
EFO:0004723	coronary artery calcification
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0005090	basophil count
EFO:0006335	systolic blood pressure
EFO:0004462	PR interval
EFO:0006946	behavioural disinhibition measurement
EFO:0004344	birth weight
EFO:0004753	interleukin 12 measurement
EFO:0004750	interleukin 10 measurement
EFO:0004810	interleukin-6 measurement
EFO:0008165	interferon gamma measurement
EFO:0008174	interleukin 17 measurement
EFO:0008184	interleukin 4 measurement
EFO:0008293	stromal cell-derived factor 1 alpha measurement
EFO:0010116	choline measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004469	HOMA-B
EFO:0005260	response to antimicrotubule agent
EFO:0004327	electrocardiography
EFO:0007828	daytime rest measurement
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004310	Double Outlet Right Ventricle	C14.240.400.560.540.500; C14.240.400.915.300; C14.280.400.560.540.500; C14.280.400.915.300; C16.131.240.400.560.540.500; C16.131.240.400.915.300
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
C565710	Diaphragmatic Hernia 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	affects methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression, increases expression	1
o,p’-DDT	increases methylation	1
nickel chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
bisphenol S	increases methylation	1
MT19c compound	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cytarabine	decreases expression	1
DDT	increases methylation	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Malathion	increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6XP	LCHi002-A	Induced pluripotent stem cell	Male
CVCL_A6XQ	LCHi002-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905	PHASE2	UNKNOWN	Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
NCT04467671	PHASE2	RECRUITING	Two-Year Study of the Safety and Efficacy of the Second-Generation Tissue Engineered Vascular Grafts
NCT00573066	PHASE1	COMPLETED	Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT04713657	PHASE1	RECRUITING	Beta-blocker Administration for Cardiomyocyte Division
NCT02590679	PHASE2/PHASE3	UNKNOWN	Multi-center Trial of Percutaneous Pulmonary Valve Implantation With Venus-p
NCT05579964	PHASE2/PHASE3	COMPLETED	The Role of Dexmedetomidine as Myocardial Protector in Pediatric Cardiac Surgery Total Correction of Tetralogy of Fallot
NCT05186415	PHASE1/PHASE2	COMPLETED	Contrast Enhanced 3D Echocardiographic Quantification of Right Ventricular Volumes in Repaired CHD
NCT07194304	EARLY_PHASE1	COMPLETED	Effect of Parenteral Alpha-Tocopherol in the Definitive Surgery of Tetralogy of Fallot
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects
NCT00005190	Not specified	COMPLETED	Reproduction and Survival After Cardiac Defect Repair
NCT00112320	Not specified	COMPLETED	Comparison of Two Pulmonary Valve Replacement Methods to Treat Tetralogy of Fallot
NCT00155428	Not specified	UNKNOWN	Biomodel in Tetralogy of Fallot
NCT00243776	Not specified	RECRUITING	Molecular and Cellular Characterization of Cardiac Tissue in Postnatal Development
NCT00266188	Not specified	COMPLETED	Follow up of Post-repair Tetralogy of Fallot
NCT00412685	Not specified	COMPLETED	Myocardial Contrast Echocardiography in Congenital Heart Disease
NCT00536432	Not specified	COMPLETED	Early Re-intervention in Infants and Small Children After Correction of Tetralogy of Fallot
NCT00860327	Not specified	TERMINATED	Examining Developmental Changes in Heart Contractions of Children With Congenital Heart Defects
NCT01419756	Not specified	COMPLETED	Assessment of Right Ventricular Volume in Tetralogy of Fallott (TOF) Patients
NCT01762124	Not specified	COMPLETED	Study of the Native Outflow Tract Transcatheter Pulmonary Valve (TPV)
NCT01824160	Not specified	COMPLETED	Pulmonary Artery Repair With Covered Stents
NCT01941576	Not specified	COMPLETED	Effects of rhBNP in Pediatrics After Corrective Repair of Tetralogy Of Fallot
NCT02161471	Not specified	COMPLETED	Haemodynamics and Function of the Atria in Congenital Heart Disease by Cardiovascular Magnetic Resonance
NCT02364934	Not specified	UNKNOWN	Pharmacokinetics and Pharmacodynamics of Rocuronium in Closed-Loop Infusion System
NCT02534792	Not specified	COMPLETED	Early Revalvulation After Fallot Repair Improves Clinical Outcome
NCT02586740	Not specified	COMPLETED	Retrospective Review of Anesthetic Considerations for Pulmonary Artery Rehabilitation
NCT02643810	Not specified	COMPLETED	Exercise Training in Adults With Corrected Tetralogy of Fallot
NCT02967315	Not specified	COMPLETED	Effects of Changes in Fluid Status on Right Ventricular Volumes and Function
NCT02968264	Not specified	COMPLETED	Tetralogy of Fallot for Life
NCT02980614	Not specified	UNKNOWN	4D Velocity Mapping of the Heart in rTOF Patients
NCT03049995	Not specified	UNKNOWN	Stress Echo 2020 - The International Stress Echo Study
NCT03130777	Not specified	ACTIVE_NOT_RECRUITING	ALTERRA: SAPIEN 3 THV With the Alterra Adaptive Prestent
NCT03234582	Not specified	UNKNOWN	Comparison of RVOT Gradient Under Anaesthesia With Post-operative Gradient in Patients Undergoing TOF Repair
NCT03275844	Not specified	UNKNOWN	Physical Capacity and Activity in Children With Congenital Heart Disease
NCT03441971	Not specified	ACTIVE_NOT_RECRUITING	Evaluation of the GORE PV1 Device in Patients With Pulmonary Valve Dysfunction
NCT03470064	Not specified	UNKNOWN	Early Right Ventricular Function After Repair Of Tetralogy Of Fallot , An Evidence Based Study.
NCT03568357	Not specified	UNKNOWN	Reoxygenation for Cyanotic Pediatric CHD