FAM20A

FAM20A golgi associated secretory pathway pseudokinase, the group of Golgi associated kinase family

Basic information

Region (hg38): 17:68535112-68601367

Links

ENSG00000108950 ∙ NCBI:54757 ∙ OMIM:611062 ∙ HGNC:23015 ∙ Uniprot:Q96MK3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amelogenesis imperfecta type 1G (Supportive), mode of inheritance: AR
• amelogenesis imperfecta type 1G (Strong), mode of inheritance: AR
• amelogenesis imperfecta type 1G (Definitive), mode of inheritance: AR
• amelogenesis imperfecta type 1G (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type IG (Enamel-renal syndrome)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental	18597613; 21549343; 21990045; 23434854; 24196488

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAM20A gene.

• not provided (162 variants)
• Amelogenesis imperfecta type 1G (45 variants)
• Inborn genetic diseases (26 variants)
• not specified (5 variants)
• Hereditary cancer-predisposing syndrome (4 variants)
• FAM20A-related condition (2 variants)
• - (2 variants)
• Acrodysostosis (1 variants)
• Carney complex (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAM20A gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	40	9	52
missense		2	55	7	5	69
nonsense	3					3
start loss						0
frameshift	6	3				9
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region	1	1	4	4	1	11
non coding		1		13	28	42
Total	10	9	61	60	42

Highest pathogenic variant AF is 0.0000985

Variants in FAM20A

This is a list of pathogenic ClinVar variants found in the FAM20A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-68537267-C-T			Benign (Feb 03, 2020)
17-68537488-A-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
17-68537493-G-A			Likely benign (Oct 24, 2023)
17-68537503-A-G		Inborn genetic diseases	Uncertain significance (May 09, 2023)
17-68537513-CA-TG			Likely benign (Mar 14, 2022)
17-68537514-A-G		not specified • Amelogenesis imperfecta type 1G	Benign (Jan 31, 2024)
17-68537531-G-A			Likely benign (Dec 25, 2022)
17-68537534-G-A			Likely benign (Mar 03, 2020)
17-68537538-A-G			Uncertain significance (Mar 19, 2022)
17-68537558-G-A			Likely benign (Sep 04, 2023)
17-68537562-A-T		Inborn genetic diseases	Likely benign (Mar 01, 2024)
17-68537592-G-A		Acrodysostosis • Carney complex • not specified	Benign/Likely benign (Jan 15, 2024)
17-68537601-C-T			Uncertain significance (Feb 20, 2022)
17-68537619-A-G			Uncertain significance (Jun 06, 2023)
17-68537624-G-T			Likely benign (Apr 30, 2018)
17-68537631-G-A		Amelogenesis imperfecta type 1G	Likely benign (Aug 27, 2023)
17-68537655-TC-T			Pathogenic (Jan 17, 2022)
17-68537671-G-A		Amelogenesis imperfecta type 1G	Pathogenic (Jan 01, 2014)
17-68537671-G-T		Hereditary cancer-predisposing syndrome	Benign/Likely benign (Nov 15, 2023)
17-68537672-C-G		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
17-68537680-C-T		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
17-68537705-C-A			Benign (Nov 14, 2023)
17-68537722-A-G			Benign (Oct 24, 2022)
17-68537725-G-A			Uncertain significance (Jul 30, 2022)
17-68537731-TC-T			Pathogenic (Aug 14, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FAM20A	protein_coding	protein_coding	ENST00000592554	11	66277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.15e-7	0.974	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0211	306	305	1.00	0.0000168	3487
Missense in Polyphen		106	121.09	0.87541		1439
Synonymous	-0.427	139	133	1.05	0.00000744	1097
Loss of Function	2.10	15	26.7	0.562	0.00000169	263

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00137	0.00136
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000243	0.000237
Middle Eastern	0.000544	0.000544
South Asian	0.000461	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals. {ECO:0000269|PubMed:25789606}.
• Disease: DISEASE: Amelogenesis imperfecta 1G (AI1G) [MIM:204690]: A disorder characterized by dental anomalies, gingival overgrowth, and nephrocalcinosis. Dental anomalies include hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay of tooth eruption, hypodontia/oligodontia, pericoronal radiolucencies and unerupted teeth. {ECO:0000269|PubMed:21549343, ECO:0000269|PubMed:21990045, ECO:0000269|PubMed:23434854, ECO:0000269|PubMed:23468644, ECO:0000269|PubMed:23697977, ECO:0000269|PubMed:24196488, ECO:0000269|PubMed:24259279, ECO:0000269|PubMed:24756937, ECO:0000269|PubMed:25636655, ECO:0000269|PubMed:25789606, ECO:0000269|PubMed:25827751}. 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)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.379
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

• pHI: 0.158
• hipred: N
• hipred_score: 0.462
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.291

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fam20a
• Phenotype: limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;protein phosphorylation;response to bacterium;biomineral tissue development;tooth eruption;calcium ion homeostasis;enamel mineralization;positive regulation of protein serine/threonine kinase activity
• Cellular component: extracellular space;cell;endoplasmic reticulum;Golgi apparatus;extracellular exosome
• Molecular function: protein serine/threonine kinase activity;protein binding;phosphotransferase activity, alcohol group as acceptor;protein serine/threonine kinase activator activity