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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FAM20A
FAM20A golgi associated secretory pathway pseudokinase
Chromosome 17 Β· 17q24.2
NCBI Gene: 54757Ensembl: ENSG00000108950.13HGNC: HGNC:23015UniProt: B7Z4Y3
29PubMed Papers
21Diseases
0Drugs
44Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein serine/threonine kinase activitytooth eruptioncalcium ion homeostasisenamel mineralizationamelogenesis imperfecta type 1GAmelogenesis imperfecta and gingival hyperplasia syndromeotosclerosisAlzheimer disease
✦AI Summary

FAM20A is a Golgi-associated pseudokinase that functions as an allosteric activator of FAM20C, a serine/threonine kinase crucial for biomineralization 1. FAM20A forms a complex with FAM20C and enhances its ability to phosphorylate secreted proteins that constitute the extracellular matrix guiding enamel mineral deposition 1. The protein is involved in calcium homeostasis and prevents ectopic calcification through proper phosphorylation of mineralization inhibitors like matrix Gla protein 2. Biallelic loss-of-function mutations in FAM20A cause amelogenesis imperfecta type 1G, also designated enamel-renal syndrome, characterized by severe enamel hypoplasia, gingival fibromatosis, intrapulpal calcifications, and nephrocalcinosis 234. FAM20A dysfunction impairs deciduous dental pulp cell proliferation, migration, and osteogenic differentiation while increasing inflammatory gene expression 5. Mechanistically, FAM20A mutations disrupt BMP signaling pathways and upregulate genes involved in ectopic mineralization in soft tissues 2. Recent bioinformatic studies identified FAM20A as a hub gene with diagnostic value in distinguishing papillary thyroid carcinoma with Hashimoto's thyroiditis background from isolated papillary thyroid carcinoma, with an ROC AUC of 0.825 6. FAM20A is quantifiable in human milk and associates with calcium metabolism proteins 7, suggesting roles beyond dental development.

Sources cited
1
FAM20A is a secreted pseudokinase needed for optimal FAM20C activity and mutations cause Enamel-Renal Syndrome
PMID: 41241263
2
Biallelic FAM20A mutations cause amelogenesis imperfecta type IG/enamel renal syndrome; upregulation of BMP signaling underlies intrapulpal calcifications; FAM20A prevents ectopic mineralization through phosphorylation of matrix Gla protein
PMID: 37159186
3
Enamel renal syndrome caused by biallelic FAM20A mutations presents with amelogenesis imperfecta, gingival hyperplasia, and nephrocalcinosis
PMID: 32835847
4
FAM20A gene variants in amelogenesis imperfecta cause structural damage to FAM20A protein; identified pathogenic nonsense, frameshift, and insertion variants
PMID: 38546520
5
FAM20A reduction in dental pulp cells reduces proliferation, migration, attachment, and osteogenic differentiation while increasing inflammatory gene expression
PMID: 38477421
6
FAM20A identified as hub gene with diagnostic value (ROC AUC 0.825) in distinguishing papillary thyroid carcinoma with Hashimoto's thyroiditis background
PMID: 39510033
7
FAM20A is a low-abundant extracellular matrix protein involved in calcium metabolism; successfully quantified in human milk using mass spectrometry proteomics
PMID: 34957696
Disease Associationsβ“˜21
amelogenesis imperfecta type 1GOpen Targets
0.81Strong
Amelogenesis imperfecta and gingival hyperplasia syndromeOpen Targets
0.37Weak
otosclerosisOpen Targets
0.33Weak
Alzheimer diseaseOpen Targets
0.26Weak
Chorioretinal scarOpen Targets
0.26Weak
cholelithiasisOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
hearing loss, mixed conductive-sensorineuralOpen Targets
0.19Weak
Carney complex, type 1Open Targets
0.15Weak
HypercholesterolemiaOpen Targets
0.14Weak
metabolic diseaseOpen Targets
0.13Weak
hyperlipidemiaOpen Targets
0.13Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
Acrodysostosis 1 with or without hormone resistanceOpen Targets
0.12Weak
familial atrial myxomaOpen Targets
0.12Weak
pigmented nodular adrenocortical disease, primary, 1Open Targets
0.12Weak
familial hyperlipidemiaOpen Targets
0.11Weak
response to statinOpen Targets
0.10Suggestive
Hypoplastic amelogenesis imperfectaOpen Targets
0.08Suggestive
amelogenesis imperfectaOpen Targets
0.08Suggestive
Amelogenesis imperfecta 1GUniProt
Pathogenic Variants44
NM_017565.4(FAM20A):c.915_918del (p.Phe305fs)Pathogenic
Amelogenesis imperfecta type 1G|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 305
NM_017565.4(FAM20A):c.590-5T>APathogenic
Amelogenesis imperfecta type 1G|not provided
β˜…β˜…β˜†β˜†2024
NM_017565.4(FAM20A):c.721C>T (p.Gln241Ter)Pathogenic
not provided|Amelogenesis imperfecta type 1G
β˜…β˜…β˜†β˜†2024β†’ Residue 241
NM_017565.4(FAM20A):c.813-2A>GPathogenic
Amelogenesis imperfecta type 1G
β˜…β˜…β˜†β˜†2024
NM_017565.4(FAM20A):c.907_908del (p.Ser303fs)Pathogenic
not provided|Amelogenesis imperfecta type 1G
β˜…β˜…β˜†β˜†2024β†’ Residue 303
NM_017565.4(FAM20A):c.1447del (p.Glu483fs)Pathogenic
not provided|Amelogenesis imperfecta type 1G
β˜…β˜…β˜†β˜†2024β†’ Residue 483
NM_017565.4(FAM20A):c.406C>T (p.Arg136Ter)Pathogenic
Amelogenesis imperfecta type 1G|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 136
NM_017565.4(FAM20A):c.752TCT[1] (p.Phe252del)Likely pathogenic
FAM20A-related disorder|Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2025β†’ Residue 252
NM_017565.4(FAM20A):c.720-2A>GPathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2025
NM_017565.4(FAM20A):c.1310del (p.Arg437fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 437
NM_017565.4(FAM20A):c.720-1G>CLikely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2025
NM_017565.4(FAM20A):c.343_362del (p.Ser115fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 115
NM_017565.4(FAM20A):c.719+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017565.4(FAM20A):c.278_281dup (p.Leu95fs)Likely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024β†’ Residue 95
NM_017565.4(FAM20A):c.1351C>T (p.Gln451Ter)Likely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024β†’ Residue 451
NM_017565.4(FAM20A):c.590-3_590-2delinsAGLikely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024
NM_017565.4(FAM20A):c.466C>T (p.Arg156Ter)Pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024β†’ Residue 156
NM_017565.4(FAM20A):c.813-1G>CLikely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024
NM_017565.4(FAM20A):c.1092_1093del (p.Leu365fs)Likely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024β†’ Residue 365
NM_017565.4(FAM20A):c.1207G>A (p.Asp403Asn)Likely pathogenic
Amelogenesis imperfecta type 1G
β˜…β˜†β˜†β˜†2024β†’ Residue 403
View on ClinVar β†—
Related Genes
AMTNProtein interaction99%AMBNProtein interaction83%ENAMProtein interaction83%PRSS23Protein interaction72%MXRA8Protein interaction72%WDR72Protein interaction71%
Tissue Expression6 tissues
Liver
100%
Lung
25%
Ovary
13%
Heart
5%
Bone Marrow
1%
Brain
1%
Gene Interaction Network
Click a node to explore
FAM20AAMTNAMBNENAMPRSS23MXRA8WDR72
PROTEIN STRUCTURE
Preparing viewer…
PDB5WRR Β· 2.51 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.11LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.66–1.11]
RankingsWhere FAM20A stands among ~20K protein-coding genes
  • #12,142of 20,598
    Most Researched29
  • #1,452of 5,498
    Most Pathogenic Variants44
  • #11,344of 17,882
    Most Constrained (LOEUF)1.11
Genes detectedFAM20A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Biomarkers associated with papillary thyroid carcinoma and Hashimoto's thyroiditis: Bioinformatic analysis and experimental validation.
PMID: 39510033
Int Immunopharmacol Β· 2024
1.00
2
FAM20C and FAM20A in normal and ectopic mineralization: A focus on oro-renal syndromes.
PMID: 41241263
Matrix Biol Β· 2025
0.90
3
Quantification of FAM20A in human milk and identification of calcium metabolism proteins.
PMID: 34957696
Physiol Rep Β· 2021
0.80
4
FAM20A-Associated Amelogenesis Imperfecta: Gene Variants with Functional Verification and Histological Features.
PMID: 38546520
Chin J Dent Res Β· 2024
0.70
5
Molecular Study of FAM20A Gene and Biochemical Analysis for Amelogenesis Imperfecta Patients.
PMID: 39661899
Wiad Lek Β· 2024
0.60