HORMAD2

Chr 22

HORMA domain containing 2

Also known as: CT46.2

NCBI Gene: 150280ENSG00000176635UniProt: Q8N7B1

Predicted to be involved in meiotic cell cycle and meiotic sister chromatid cohesion. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

55
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HORMAD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 28 VUS of 55 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.99LOEUF
pLI 0.000
Z-score 1.61
OE 0.57 (0.34–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.86 (0.74–0.99)
128 obs / 149.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.34–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.74–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 9 / 15.9Missense obs/exp: 128 / 149.6Syn Z: -0.14

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS28
Likely Benign2
Benign1
18
Pathogenic
1
Likely Pathogenic
28
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
26
2
0
28
Likely Benign
0
2
0
0
2
Benign
0
1
0
0
1
Total02921050

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HORMAD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy.
Wang YN et al.·Kidney Int
2023
Genome-wide association study of pulpal and apical diseases.
Salminen A et al.·Nat Commun
2025
Genetic study of Hormad1 and Hormad2 with non-obstructive azoospermia patients in the male Chinese population.
Song B et al.·J Assist Reprod Genet
2014Cohort
A homozygous stop codon in HORMAD2 in a patient with recurrent digynic triploid miscarriage.
Liang M et al.·Mol Genet Genomic Med
2024
Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy.
Feenstra B et al.·J Med Genet
2017
The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular Mechanisms.
Suzuki Y et al.·Kidney360
2021Review
IgA Nephropathy Susceptibility Loci and Disease Progression.
Shi M et al.·Clin J Am Soc Nephrol
2018
Human hepatic gene expression signature of non-alcoholic fatty liver disease progression, a meta-analysis.
Ryaboshapkina M et al.·Sci Rep
2017Meta-analysis
Genome-wide DNA methylation and RNA expression differences correlate with invasiveness in melanoma cell lines.
Motwani J et al.·Epigenomics
2021
Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?
Batista-Liz JC et al.·Int J Mol Sci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools