GZF1
protein-codingGDNF inducible zinc finger protein 1, the group of Zinc fingers C2H2-type|BTB domain containing
Gene summary
Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]
- ZNF336
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0060556
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0060556
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0060556
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0060556
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0007875
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Musculoskeletal; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Individuals are at risk for ophthalmologic features such as retinal detachment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GZF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022482.5. 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 | 84 | 1 | 86 | ||
| missense | 137 | 7 | 3 | 147 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 8 | 3 | 5 | 16 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 11 | 4 | 144 | 91 | 4 | 254 |
Highest pathogenic variant AF is 0.0000030976707
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071927.1 | 5 | MANE Select | |
| Ensembl | ENSP00000338290.5 | 5 | MANE Select | |
| RefSeq | NP_001303941.1 | 5 | Standard | |
| RefSeq | NP_001303948.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- branching involved in ureteric bud morphogenesis
- negative regulation of transcription, DNA-templated
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II distal enhancer sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- sequence-specific DNA binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338121
- Coding exons
- 5
- Length
- 10914
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.95 | 323 | 438 | 0.738 | 0.0000271 | 4720 |
| Missense (PolyPhen) | 91 | 175.43 | 0.51874 | 1862 | ||
| Synonymous | 0.434 | 175 | 182 | 0.959 | 0.0000126 | 1337 |
| Loss of Function | 2.88 | 9 | 24.3 | 0.370 | 0.00000120 | 316 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor that binds the GZF1 responsive element (GRE) (consensus: 5'-TGCGCN[TG][CA]TATA-3'). May be regulating VSX2/HOX10 expression. {ECO:0000269|PubMed:14522971, ECO:0000269|PubMed:16049025}.;
- Disease
- DISEASE: Joint laxity, short stature, and myopia (JLSM) [MIM:617662]: An autosomal recessive disease characterized by generalized joint laxity, joint dislocation, pectus carinatum, short stature, and severe myopia with retinal detachment. {ECO:0000269|PubMed:28475863}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.527
- RVIS EVS
- -0.57
- RVIS percentile EVS
- 18.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.494
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |