ZMYM2
protein-codingzinc finger MYM-type containing 2, the group of Zinc fingers MYM-type
Gene summary
The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex. Translocation of this gene with the fibroblast growth factor receptor-1 gene (FGFR1) results in a fusion gene, which may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]
- ZNF198
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~133.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019719
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0019719
Submitter: Franklin by Genoox
Total 14 different heterozygous loss-of-function mutations in ZMYM2 gene in 15 unrelated Congenital anomalies of the kidney and urinary tract affected families were identified. These findings establish that loss-of-function mutations of ZMYM2 gene may cause of human CAKUT.
Inheritance Pattern: AD
Disease ID:MONDO:0859190
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0859190
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0800439
Submitter: ClinGen
*ZMYM2* was first reported in association with syndromic urinary tract malformations in 2020 (Connaughton et al. PMID: 32891193). Phenotypic features include congenital malformations of the kidney and urinary tract, cardiac defects, dysmorphic features, global developmental delay, variable intellectual disability, and autism spectrum disorder. Less common findings include hypotonia, microcephaly, and seizures. All individuals reported with renal malformations also had neurologic features. Some individuals have isolated neurodevelopmental features without congenital malformations. This curation includes 10 heterozygous loss of function variants (6 nonsense, 3 frameshift, 1 splice site) that are reported in 10 individuals with phenotypic similarity (PMIDs: 32891193, 37383123). Of these 10 variants, 2 have functional data to support a loss of function effect. All distinct variants available in the literature in association with congenital malformations of the kidney and urinary tract with neurodevelopmental delays are scored. Additional probands are reported in the literature, but as the maximum score for genetic evidence (12 points) has already been reached, those individuals were not included in this curation. There are also additional probands reported in the literature harboring heterozygous putative loss of function variants in association with cerebral palsy and schizophrenia. These were not scored. In summary, there is definitive evidence supporting the relationship between *ZMYM2* and autosomal dominant syndromic complex neurodevelopmental disorder. This has been repeatedly demonstrated in the clinical diagnostic setting, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on the meeting date May 22, 2025 (SOP Version 10).
Inheritance Pattern: AD
Disease ID:MONDO:0859190
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0859190
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal
Intervention: Cardiovascular; Renal
Rationale: Among other findings, individuals may have congenital cardiovascular and renal anomalies, which may lead to sequelae, and awareness may allow prompt diagnosis and medical or surgical management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZMYM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_197968.4. 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 | 3 | 22 | 5 | 30 | ||
| missense | 261 | 11 | 1 | 273 | ||
| nonsense | 16 | 27 | 7 | 50 | ||
| start loss | 0 | |||||
| frameshift | 29 | 28 | 18 | 75 | ||
| splice donor/acceptor (+/-2bp) | 2 | 13 | 9 | 24 | ||
| Total | 47 | 68 | 298 | 33 | 6 | 452 |
Highest pathogenic variant AF is 0.00008718806
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_932072.1 | 23 | MANE Select | |
| Ensembl | ENSP00000479904.1 | 23 | MANE Select | |
| RefSeq | NP_001177893.1 | 23 | Standard | |
| RefSeq | NP_001177894.1 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- Signaling by FGFR in disease
- Signaling by cytosolic FGFR1 fusion mutants
- FGFR1 mutant receptor activation
- Signaling by FGFR1 in disease
Biological Process
- regulation of transcription by RNA polymerase II
- biological_process
- peptidyl-tyrosine phosphorylation
- regulation of cell morphogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- protein tyrosine kinase activity
- protein binding
- zinc ion binding
- ubiquitin conjugating enzyme binding
Cellular Component
- nucleus
- cytosol
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382869
- Coding exons
- 23
- Length
- 133159
- Individuals with no LoFs
- 125671
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125696
- p
- 0.0000995
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.01 | 451 | 671 | 0.672 | 0.0000324 | 9073 |
| Missense (PolyPhen) | 109 | 257.93 | 0.4226 | 3605 | ||
| Synonymous | 1.17 | 211 | 234 | 0.903 | 0.0000119 | 2483 |
| Loss of Function | 6.06 | 15 | 69.5 | 0.216 | 0.00000395 | 895 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00017 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May function as a transcription factor.;
- Disease
- DISEASE: Note=A chromosomal aberration involving ZMYM2 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with FGFR1. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow. {ECO:0000269|PubMed:9716603}.;
Recessive Scores
- pRec
- 0.210
Intolerance Scores
- LoFtool
- 0.773
- RVIS EVS
- -1.28
- RVIS percentile EVS
- 5.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.951
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |