HORMAD2
protein-codingHORMA domain containing 2
Gene summary
Predicted to be involved in meiotic recombination checkpoint signaling; meiotic sister chromatid cohesion; and synaptonemal complex assembly. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~96.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HORMAD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152510.4. 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 | 0 | |||||
| missense | 26 | 2 | 1 | 29 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 26 | 2 | 1 | 29 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689723.1 | 10 | MANE Select | |
| Ensembl | ENSP00000336984.6 | 10 | MANE Select | |
| RefSeq | NP_001316386.1 | 10 | Standard | |
| RefSeq | NP_001316387.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- meiotic sister chromatid cohesion
- meiotic cell cycle
Cellular Component
- synaptonemal complex
- nucleus
- chromosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336726
- Coding exons
- 10
- Length
- 96902
- Individuals with no LoFs
- 124325
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 253
- Defined
- 124580
- p
- 0.00102
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.627 | 128 | 150 | 0.856 | 0.00000717 | 2043 |
| Missense (PolyPhen) | 37 | 53.098 | 0.69682 | 739 | ||
| Synonymous | -0.143 | 53 | 51.7 | 1.03 | 0.00000249 | 526 |
| Loss of Function | 1.61 | 9 | 15.9 | 0.565 | 8.46e-7 | 214 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00041 | 0.00039 | rare |
| Latino/Admixed American | 0.00076 | 0.00070 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0036 | 0.0035 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00071 | 0.00059 | rare |
| South Asian | 0.0030 | 0.0028 | notable |
| Other | 0.0018 | 0.0017 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes. Required for the DNA double-strand break-independent, BRCA1-dependent activation of ATR on the sex chromosomes that is essential for normal sex body formation (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0945
Intolerance Scores
- LoFtool
- 0.785
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.260
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |