GeneBe

FAM20A

protein-coding

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

Gene summary

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]

MANE transcript

NM_017565.4

Inheritance

AR

ClinVar variants

P:46U:166B:86

Top phenotype

Amelogenesis imperfecta, type IG (Enamel-renal syndrome)

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr17:68,535,113-68,601,367

External References & Databases

Ensembl (ENSG00000108950)NCBI Gene (54757)OMIM (611062)HGNC:23015GenCCUniProt (Q96MK3)AlphaFoldClinVar (FAM20A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~66.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 1GSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008771

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta type 1GSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008771

Submitter: Ambry Genetics

amelogenesis imperfecta type 1GSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008771

Submitter: Orphanet

amelogenesis imperfecta type 1GSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008771

Submitter: PanelApp Australia

amelogenesis imperfecta type 1GDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008771

Submitter: G2P

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IG (Enamel-renal syndrome)AR

Manifestation: Dental

Intervention: General

Rationale: 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

Refs: 18597613; 21549343; 21990045; 23434854; 24196488Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAM20A variants in ClinVar

12 Conditions Cataloged
not providedTotal: 182
Amelogenesis imperfecta type 1GTotal: 143
Inborn genetic diseasesTotal: 86
not specifiedTotal: 25
FAM20A-related disorderTotal: 22
Hereditary cancer-predisposing syndromeTotal: 4
FAM20A-related disordersTotal: 4
Carney complex, type 1Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017565.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
68
clinvar
1
clinvar
 73
missense
3
clinvar
159
clinvar
16
clinvar
1
clinvar
 179
nonsense
6
clinvar
4
clinvar
 10
start loss
0
frameshift
14
clinvar
7
clinvar
1
clinvar
 22
splice donor/acceptor (+/-2bp)
5
clinvar
7
clinvar
2
clinvar
 14
Total2521166842298

Highest pathogenic variant AF is 0.007773696

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_017565.4RefSeqNP_060035.211MANE Select
ENST00000592554.2EnsemblENSP00000468308.111MANE Select
NM_001243746.2RefSeqNP_001230675.110Standard
ENST00000590074.5EnsemblENSP00000464910.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • positive regulation of protein phosphorylation
  • protein phosphorylation
  • response to bacterium
  • biomineral tissue development
  • tooth eruption

Molecular Function

  • protein serine/threonine kinase activity
  • protein binding
  • phosphotransferase activity, alcohol group as acceptor
  • protein serine/threonine kinase activator activity

Cellular Component

  • extracellular space
  • cell
  • endoplasmic reticulum
  • Golgi apparatus
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000592554
Coding exons
11
Length
66277
Individuals with no LoFs
125667
Homozygous LoFs
0
Heterozygous LoFs
81
Defined
125748
p
0.000322
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.02113063051.000.00001683487
Missense (PolyPhen)106121.090.875411439
Synonymous-0.4271391331.050.000007441097
Loss of Function2.101526.70.5620.00000169263

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00100.0010notable
Latino/Admixed American0.000320.00032rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000540.00054rare
Finnish00.0absent
European (Non-Finnish)0.000240.00024rare
South Asian0.000460.00046rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.111

Intolerance Scores

LoFtool
0.379
RVIS EVS
-0.36
RVIS percentile EVS
29.31

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.291

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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