NOG

Chr 17AD

noggin

Also known as: SYM1, SYNS1, SYNS1A

NCBI Gene: 9241ENSG00000183691UniProt: Q13253OMIM: 602991

The protein is a secreted inhibitor of bone morphogenetic proteins (BMPs) that is essential for neural tube development, cartilage morphogenesis, and joint formation. Mutations cause proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1), both characterized by multiple joint fusions, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function mutations, reflecting its critical role in early development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.425 OMIM phenotypes
Clinical Summary— NOG
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Gene-Disease Validity (ClinGen)
NOG-related symphalangism spectrum disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.890
Z-score 2.48
OE 0.00 (0.00–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.32Z-score
OE missense 0.68 (0.58–0.81)
94 obs / 137.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.42)
0≤0.351.4
Missense OE0.68 (0.58–0.81)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 0 / 7.2Missense obs/exp: 94 / 137.5Syn Z: -0.56
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNOG-related-symphalangism spectrum disorderLOFAD
DN
0.3793th %ile
GOF
0.1799th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.42

Literature Evidence

LOFAutosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding nogginPMID:12089654

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NOG · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Humanized-liver TK-NOG mice lacking plasma carboxylesterase 1c improve the prediction of human carboxylesterase 1-mediated drug metabolism.
Uehara S et al.·Drug Metab Dispos
2026
A humanized NOG-EXL mouse model for producing severe fever with thrombocytopenia syndrome virus-reactive human antibodies.
Lee DH et al.·Animal Model Exp Med
2026Open AccessFunctional
Repeated surgical oocyte collection from severe immunodeficient NOG mice after repeated superovulation with inhibin antiserum and eCG.
Takezawa K et al.·Exp Anim
2026
The Suggestive Association Between the NOG rs227731 Polymorphism and Non-Syndromic Cleft Lip With or Without Palate Subtypes in a Japanese Cohort.
Anh LK et al.·Congenit Anom (Kyoto)
2026Cohort
Variants Near NOG and SOX9 Are Associated with Mandibular Retrognathia.
Juuri E et al.·J Dent Res
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients