FAM20A

Chr 17AR

FAM20A golgi associated secretory pathway pseudokinase

Also known as: AI1G, AIGFS, FP2747

NCBI Gene: 54757ENSG00000108950UniProt: Q96MK3

This locus encodes a protein that is likely secreted and may function in hematopoiesis. A mutation at this locus has been associated with amelogenesis imperfecta and gingival hyperplasia syndrome. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IG (enamel-renal syndrome)MIM #204690
AR
1
Active trials
59
Pathogenic / LP
374
ClinVar variants
17
Pubs (1 yr)
-0.0
Missense Z
0.86
LOEUF
Clinical Summary— FAM20A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 174 VUS of 374 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.10
OE 0.56 (0.38–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.02Z-score
OE missense 1.00 (0.91–1.10)
306 obs / 305.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.38–0.86)
0≤0.351.4
Missense OE1.00 (0.91–1.10)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 15 / 26.7Missense obs/exp: 306 / 305.0Syn Z: -0.43
DN
DN
0.6743th %ile
GOF
0.5072th %ile
LOF
0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic22
VUS174
Likely Benign91
Benign40
Conflicting10
37
Pathogenic
22
Likely Pathogenic
174
VUS
91
Likely Benign
40
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
20
0
37
Likely Pathogenic
12
2
8
0
22
VUS
1
154
17
2
174
Likely Benign
0
10
22
59
91
Benign
0
4
29
7
40
Conflicting
—10
Total301709668374

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

View in ClinVar →

FAM20A · protein map & ClinVar variants

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

Gene2Phenotype Curations

FAM20A-related amelogenesis imperfecta and gingival fibromatosis syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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