NOBOX

Chr 7AD

NOBOX oogenesis homeobox

Also known as: OG-2, OG2, OG2X, POF5, TCAG_12042

NCBI Gene: 135935ENSG00000106410UniProt: O60393

This homeobox gene encodes a transcription factor that is thought to play a role in oogenesis. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes. Defects in this gene result in premature ovarian failure type 5.[provided by RefSeq, May 2011]

Primary Disease Associations & Inheritance

Premature ovarian failure 5MIM #611548
AD
271
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NOBOX
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 140 VUS of 271 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.
0.76LOEUF
pLI 0.000
Z-score 2.49
OE 0.47 (0.30–0.76)
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.
0.48Z-score
OE missense 0.93 (0.85–1.02)
358 obs / 384.6 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.0.47 (0.30–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.85–1.02)
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.0.91
0≤1.21.6
LoF obs/exp: 12 / 25.6Missense obs/exp: 358 / 384.6Syn Z: 0.87

ClinVar Variant Classifications

271 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic8
VUS140
Likely Benign27
Benign32
Conflicting7
57
Pathogenic
8
Likely Pathogenic
140
VUS
27
Likely Benign
32
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
51
0
57
Likely Pathogenic
1
3
4
0
8
VUS
1
98
38
3
140
Likely Benign
0
8
11
8
27
Benign
0
8
24
0
32
Conflicting
—7
Total711812811271

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

View in ClinVar →

Protein Context — Lollipop Plot

NOBOX · 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

Premature ovarian failure 5

MIM #611548

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants.
Luo W et al.·J Ovarian Res
2023Cohort
Oocyte/zygote/embryo maturation arrest: a clinical study expanding the phenotype of NOBOX variants.
Van Der Kelen A et al.·J Assist Reprod Genet
2025
Screening of premature ovarian insufficiency associated genes in Hungarian patients with next generation sequencing.
Illés A et al.·BMC Med Genomics
2024Cohort
NOBOX gene variants in premature ovarian insufficiency: ethnicity-dependent insights.
Jordan P et al.·J Assist Reprod Genet
2024
A homozygous NOBOX truncating variant causes defective transcriptional activation and leads to primary ovarian insufficiency.
Li L et al.·Hum Reprod
2017
Reclassifying NOBOX variants in primary ovarian insufficiency cases with a corrected gene model and a novel quantitative framework.
Veitia RA et al.·Hum Reprod
2025Cohort
Hypo-Hydroxymethylation of Nobox is Associated with Ovarian Dysfunction in Rat Offspring Exposed to Prenatal Hypoxia.
Yao C et al.·Reprod Sci
2022
Genetic variants in diminished ovarian reserve and premature ovarian insufficiency: implications for assisted reproductive outcomes.
Xu Q et al.·J Assist Reprod Genet
2025
Selected Genetic Factors Associated with Primary Ovarian Insufficiency.
Chen M et al.·Int J Mol Sci
2023Review
Compound heterozygous null mutations of NOBOX in sisters with delayed puberty and primary amenorrhea.
Sassi A et al.·Mol Genet Genomic Med
2021Case report
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