FAM20C

Chr 7AR

FAM20C golgi associated secretory pathway kinase

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

NCBI Gene: 56975 ENSG00000177706 UniProt: Q8IXL6 OMIM: 611061

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the family of secreted protein kinases. The encoded protein binds calcium and phosphorylates proteins involved in bone mineralization. Mutations in this gene are associated with the autosomal recessive disorder Raine syndrome. [provided by RefSeq, Apr 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.491 OMIM phenotype

Clinical Summary— FAM20C

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Gene-Disease Validity (ClinGen)

lethal osteosclerotic bone dysplasia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 191 VUS of 582 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.315

Z-score 3.30

OE 0.23 (0.12–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.02Z-score

OE missense 0.84 (0.76–0.93)

263 obs / 314.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.12–0.49)

0≤0.351.4

Missense OE?0.84 (0.76–0.93)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 5 / 21.5Missense obs/exp: 263 / 314.0Syn Z: -0.39

ClinVar Variant Classifications

582 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic8

VUS191

Likely Benign249

Benign87

Conflicting16

Pathogenic

Likely Pathogenic

191

VUS

249

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	7	4	0	21
Likely Pathogenic	2	6	0	0	8
VUS	5	173	13	0	191
Likely Benign	0	10	105	134	249
Benign	1	5	70	11	87
Conflicting	—				16
Total	18	201	192	145	572

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 68) ClinVar copy-number / structural variants overlap FAM20C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →