ZFPM1
protein-codingzinc finger protein, FOG family member 1, the group of Zinc fingers C2HC-type|Zinc fingers C2H2-type|MicroRNA protein coding host genes|SET domain containing|PR/SET domain family
Gene summary
Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and transcription corepressor activity. Involved in platelet formation; regulation of definitive erythrocyte differentiation; and regulation of gene expression. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~83.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*ZFPM1* was first reported in relation to autosomal dominant congenital heart disease in 2019 (Alankarage et al., PMID: 30293987). At least three unique variants (1 missense, 2 frameshift) were reported in three individuals with CHD (PMID: 30293987, 34328347), but only one of them with a frameshift variant was included in this curation. The other two were not scored due to high minor allele frequency (>0.00001) on gnomAD v.4.1.0. This gene-disease relationship is also supported by evidence showing localized expression in the developing heart in mouse embryo, protein interaction studies with GATA4, a null mouse model showing heart defects, and a rescue in morpholino knockdown zebrafish embryos with murine *Fog1* (PMID: 14614148, 16316643). In summary, there is limited evidence supporting the relationship between *ZFPM1* and autosomal dominant congenital heart disease. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date July 8th, 2024 (SOP Version 10)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZFPM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153813.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 11 | 1 | 13 | ||
| missense | 283 | 10 | 2 | 295 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 286 | 21 | 3 | 310 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_722520.2 | 10 | MANE Select | |
| Ensembl | ENSP00000326630.2 | 10 | MANE Select | |
| Ensembl | ENSP00000480412.1 | 5 | Standard | |
| Ensembl | ENSP00000480412.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| zfpm1 | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Generic Transcription Pathway
- Factors involved in megakaryocyte development and platelet production
- RNA Polymerase II Transcription
- RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
Biological Process
- negative regulation of transcription by RNA polymerase II
- T-helper cell lineage commitment
- outflow tract morphogenesis
- atrioventricular valve morphogenesis
- mitral valve formation
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II transcription factor binding
- RNA polymerase II activating transcription factor binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- transcriptional repressor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319555
- Coding exons
- 10
- Length
- 83700
- Individuals with no LoFs
- 125242
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 69
- Defined
- 125311
- p
- 0.000275
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0470 | 437 | 434 | 1.01 | 0.0000276 | 6159 |
| Missense (PolyPhen) | 121 | 137.07 | 0.88274 | 1710 | ||
| Synonymous | -2.64 | 253 | 205 | 1.23 | 0.0000149 | 2160 |
| Loss of Function | 3.52 | 6 | 25.0 | 0.240 | 0.00000116 | 350 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.0029 | 0.0029 | notable |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2 (By similarity). {ECO:0000250}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.919
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |