FAM20C

Chr 7AR

FAM20C golgi associated secretory pathway kinase

Also known as: DMP-4, DMP4, G-CK, GEF-CK, RNS

FAM20C encodes a Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins and plays a key role in biomineralization of bones and teeth, as well as maintaining endoplasmic reticulum homeostasis. Mutations cause Raine syndrome, an autosomal recessive disorder affecting skeletal development and mineralization. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.489), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.491 OMIM phenotype
Clinical SummaryFAM20C
🧬
Gene-Disease Validity (ClinGen)
lethal osteosclerotic bone dysplasia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 32 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.315
Z-score 3.30
OE 0.23 (0.120.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.02Z-score
OE missense 0.84 (0.760.93)
263 obs / 314.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.120.49)
00.351.4
Missense OE0.84 (0.760.93)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 5 / 21.5Missense obs/exp: 263 / 314.0Syn Z: -0.39

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS32
Likely Benign57
Benign1
Conflicting1
5
Pathogenic
4
Likely Pathogenic
32
VUS
57
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
3
0
5
Likely Pathogenic
2
2
0
0
4
VUS
0
30
2
0
32
Likely Benign
0
1
17
39
57
Benign
0
1
0
0
1
Conflicting
1
Total3352239100

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

View in ClinVar →

Protein Context — Lollipop Plot

FAM20C · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗