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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NOG
noggin
Chromosome 17 Β· 17q22
NCBI Gene: 9241Ensembl: ENSG00000183691.6HGNC: HGNC:7866UniProt: Q13253
113PubMed Papers
25Diseases
0Drugs
50Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of cell migrationembryonic skeletal system developmentnegative regulation of BMP signaling pathwaynegative regulation of osteoblast differentiationproximal symphalangism 1Abrachydactyly type B2multiple synostoses syndrome 1tarsal-carpal coalition syndrome
✦AI Summary

NOG encodes noggin, a secreted polypeptide that functions as an inhibitor of bone morphogenetic proteins (BMP) signaling, which is essential for growth and patterning during human development, particularly in cartilage and bone formation 1. The protein plays a critical role in regulating multiple signaling pathways, with its hallmark clinical feature being proximal symphalangism, characterized by abnormal fusion of the proximal interphalangeal joints of the hands and feet 1. Mechanistically, noggin inhibits chondrocyte differentiation through interactions with growth differentiation factors and negatively regulates SMAD protein signaling pathways. Mutations in NOG cause a spectrum of autosomal dominant syndromes including proximal symphalangism, multiple synostoses syndrome 1, stapes ankylosis with broad thumbs and toes, tarsal-carpal coalition syndrome, and brachydactyly type B2 1. Clinical variants such as 672 C/A and 567 G/C have been associated with mandibular micrognathism 2. The overlapping phenotypic spectrum of NOG-related disorders has led to the proposed unifying term 'NOG-related symphalangism spectrum disorder (NOG-SSD)' for improved clinical recognition 1. Additionally, Myo/Nog cells expressing noggin have been identified in retinal tissues where they provide neuroprotective effects against hypoxia-induced cell death 3.

Sources cited
1
NOG encodes noggin, a secreted polypeptide important for regulating signaling pathways during development, with proximal symphalangism as the hallmark feature
PMID: 21538686
2
NOG mutations cause five autosomal dominant syndromes with overlapping characteristics, leading to the proposed unifying term NOG-SSD
PMID: 21538686
3
Clinical variants 672 C/A and 567 G/C in NOG gene are associated with mandibular micrognathism
PMID: 34592770
4
Myo/Nog cells expressing noggin provide neuroprotective effects against hypoxia-induced cell death in retinal tissues
PMID: 26688580
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜25
proximal symphalangism 1AOpen Targets
0.78Strong
brachydactyly type B2Open Targets
0.77Strong
multiple synostoses syndrome 1Open Targets
0.76Strong
tarsal-carpal coalition syndromeOpen Targets
0.76Strong
stapes ankylosis with broad thumbs and toesOpen Targets
0.73Strong
genetic disorderOpen Targets
0.49Moderate
NOG-related symphalangism spectrum disorderOpen Targets
0.46Moderate
multiple synostoses syndromeOpen Targets
0.37Weak
proximal symphalangismOpen Targets
0.37Weak
Progressive visual lossOpen Targets
0.34Weak
amyotrophic lateral sclerosisOpen Targets
0.33Weak
placenta praeviaOpen Targets
0.29Weak
cleft lipOpen Targets
0.29Weak
ventral herniaOpen Targets
0.29Weak
diaphragmatic herniaOpen Targets
0.27Weak
Umbilical herniaOpen Targets
0.27Weak
Bethlem myopathy 2Open Targets
0.27Weak
osteoarthritisOpen Targets
0.26Weak
Incisional herniaOpen Targets
0.26Weak
osteoarthritis, kneeOpen Targets
0.26Weak
Brachydactyly B2UniProt
Multiple synostoses syndrome 1UniProt
Stapes ankylosis with broad thumb and toesUniProt
Symphalangism, proximal 1AUniProt
Tarsal-carpal coalition syndromeUniProt
Pathogenic Variants50
NM_005450.6(NOG):c.665A>G (p.Tyr222Cys)Pathogenic
Proximal symphalangism 1A|Tarsal-carpal coalition syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 222
NM_005450.6(NOG):c.509C>T (p.Pro170Leu)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 170
NM_005450.6(NOG):c.328C>T (p.Gln110Ter)Pathogenic
Stapes ankylosis with broad thumbs and toes|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 110
NM_005450.6(NOG):c.104C>G (p.Pro35Arg)Pathogenic
Tarsal-carpal coalition syndrome|Proximal symphalangism 1A|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 35
NM_005450.6(NOG):c.379G>T (p.Glu127Ter)Pathogenic
Brachydactyly type B2|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 127
NM_005450.6(NOG):c.343del (p.Ala115fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 115
NM_005450.6(NOG):c.149_150del (p.Pro50fs)Likely pathogenic
Bethlem myopathy 2
β˜…β˜†β˜†β˜†2025β†’ Residue 50
NM_005450.6(NOG):c.605_615dup (p.Arg206fs)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 206
NM_005450.6(NOG):c.581dup (p.Ser195fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 195
NM_005450.6(NOG):c.167C>G (p.Pro56Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 56
NM_005450.6(NOG):c.461del (p.Phe154fs)Pathogenic
Symphalangism-brachydactyly syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 154
NM_005450.6(NOG):c.449G>A (p.Trp150Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 150
NM_005450.6(NOG):c.613dup (p.Trp205fs)Pathogenic
Stapes ankylosis with broad thumbs and toes
β˜…β˜†β˜†β˜†2024β†’ Residue 205
NM_005450.6(NOG):c.355G>T (p.Glu119Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 119
NM_005450.6(NOG):c.551G>C (p.Cys184Ser)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 184
NM_005450.6(NOG):c.621T>A (p.Cys207Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 207
NM_005450.6(NOG):c.613T>C (p.Trp205Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 205
NM_005450.6(NOG):c.553T>C (p.Ser185Pro)Likely pathogenic
Stapes ankylosis with broad thumbs and toes
β˜…β˜†β˜†β˜†2023β†’ Residue 185
NM_005450.6(NOG):c.470T>A (p.Val157Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 157
NM_005450.6(NOG):c.613T>G (p.Trp205Gly)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 205
View on ClinVar β†—
Related Genes
BGLAPProtein interaction100%FGF8Protein interaction100%FGF13Protein interaction100%SHHProtein interaction100%GDF7Protein interaction97%EGFProtein interaction97%
Tissue Expression6 tissues
Brain
100%
Lung
52%
Heart
13%
Bone Marrow
9%
Liver
3%
Ovary
3%
Gene Interaction Network
Click a node to explore
NOGBGLAPFGF8FGF13SHHGDF7EGF
PROTEIN STRUCTURE
Preparing viewer…
PDB1M4U Β· 2.42 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.37Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.12 [0.05–0.37]
RankingsWhere NOG stands among ~20K protein-coding genes
  • #4,194of 20,598
    Most Researched113 Β· top quartile
  • #1,334of 5,498
    Most Pathogenic Variants50 Β· top quartile
  • #1,681of 17,882
    Most Constrained (LOEUF)0.37 Β· top 10%
Genes detectedNOG
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Bispecific immune cell engager enhances the anticancer activity of CD16+ NK cells and macrophages in vitro, and eliminates cancer metastasis in NK humanized NOG mice.
PMID: 38490714
J Immunother Cancer Β· 2024
1.00
2
Clinical and Molecular Study of the NOG Gene in Families with Mandibular Micrognathism.
PMID: 34592770
Eur J Dent Β· 2021
0.90
3
A comprehensive review of reported heritable noggin-associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG-related-symphalangism spectrum disorder (NOG-SSD).
PMID: 21538686
Hum Mutat Β· 2011
0.80
4
Human interleukin-4-dependent facilitation of human IgG production in PBL-NOG-hIL-4-Tg mice.
PMID: 41383609
Front Immunol Β· 2025
0.70
5
Mice with human livers.
PMID: 24042096
Gastroenterology Β· 2013
0.60