FAM20C

FAM20C golgi associated secretory pathway kinase, the group of Golgi associated kinase family

Basic information

Region (hg38): 7:192571-260772

Links

ENSG00000177706 ∙ NCBI:56975 ∙ OMIM:611061 ∙ HGNC:22140 ∙ Uniprot:Q8IXL6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal osteosclerotic bone dysplasia (Definitive), mode of inheritance: AR
• lethal osteosclerotic bone dysplasia (Strong), mode of inheritance: AR
• lethal osteosclerotic bone dysplasia (Moderate), mode of inheritance: AR
• lethal osteosclerotic bone dysplasia (Strong), mode of inheritance: AR
• lethal osteosclerotic bone dysplasia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis (Raine syndrome)	AR	Renal	The condition includes hypophosphatemia an urinary phosphate wasting, and medical management (with oral phosphate supplements) has been described, and may be beneficial	Craniofacial; Dental; Musculoskeletal; Neurologic; Renal	2614802; 2020859; 12868469; 14564151; 17924334; 19250384; 20825432; 23325605

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAM20C gene.

• not_provided (364 variants)
• Inborn_genetic_diseases (104 variants)
• Lethal_osteosclerotic_bone_dysplasia (37 variants)
• FAM20C-related_disorder (25 variants)
• not_specified (7 variants)
• Cortical_dysplasia (1 variants)
• ketotic_hypoglycaemia (1 variants)
• Abnormal_facial_shape (1 variants)
• Severe_brain_malformation (1 variants)
• Neonatal_death (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAM20C gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020223.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				125	7	132
missense	6	9	159	16	3	193
nonsense	4	1	1			6
start loss						0
frameshift	3	2	2			7
splice donor/acceptor (+/-2bp)	2		1			3
Total	15	12	163	141	10

Highest pathogenic variant AF is 0.00000685414

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FAM20C	protein_coding	protein_coding	ENST00000313766	10	107743

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.315	0.685	123791	0	3	123794	0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	263	314	0.838	0.0000202	3724
Missense in Polyphen		65	101.37	0.64123		1191
Synonymous	-0.386	150	144	1.04	0.0000104	1189
Loss of Function	3.30	5	21.5	0.232	9.20e-7	265

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000303	0.0000303
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000902	0.00000891
Middle Eastern	0.00	0.00
South Asian	0.0000330	0.0000329
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth (PubMed:22582013, PubMed:23754375, PubMed:25789606). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (PubMed:26091039). Mainly phosphorylates proteins within the Ser- x-Glu/pSer motif, but also displays a broader substrate specificity (PubMed:26091039). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:22582013, PubMed:25789606). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (PubMed:26091039). {ECO:0000269|PubMed:22582013, ECO:0000269|PubMed:23754375, ECO:0000269|PubMed:25789606, ECO:0000269|PubMed:26091039}.
• Disease: DISEASE: Raine syndrome (RNS) [MIM:259775]: Autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly. {ECO:0000269|PubMed:17924334, ECO:0000269|PubMed:22582013, ECO:0000269|PubMed:25789606}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Intolerance Scores

• loftool: 0.167
• rvis_EVS: 1.57
• rvis_percentile_EVS: 95.71

Haploinsufficiency Scores

• pHI: 0.0756
• hipred: N
• hipred_score: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fam20c
• Phenotype: digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protein phosphorylation;positive regulation of bone mineralization;biomineral tissue development;osteoclast maturation;regulation of fibroblast growth factor receptor signaling pathway;post-translational protein modification;cellular protein metabolic process;positive regulation of osteoblast differentiation;ATP metabolic process;regulation of phosphorus metabolic process;enamel mineralization;odontoblast differentiation;dentinogenesis
• Cellular component: extracellular space;endoplasmic reticulum lumen;Golgi apparatus;extracellular exosome
• Molecular function: protein serine/threonine kinase activity;calcium ion binding;protein binding;ATP binding;phosphotransferase activity, alcohol group as acceptor;manganese ion binding