FAM20A

Summary

FAM20A (FAM20A golgi associated secretory pathway pseudokinase, HGNC:23015) is a protein-coding gene on chromosome 17q24.2, encoding Pseudokinase FAM20A (Q96MK3). Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth.

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.

Source: NCBI Gene 54757 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta type 1G (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 364 total — 27 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_017565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23015
Approved symbol	FAM20A
Name	FAM20A golgi associated secretory pathway pseudokinase
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434F2322
Ensembl gene	ENSG00000108950
Ensembl biotype	protein_coding
OMIM	611062
Entrez	54757

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000226094, ENST00000375556, ENST00000590074, ENST00000590873, ENST00000592554, ENST00000592847, ENST00000619787, ENST00000882123, ENST00000882124, ENST00000882125, ENST00000882126, ENST00000913497, ENST00000958307

RefSeq mRNA: 2 — MANE Select: NM_017565 NM_001243746, NM_017565

CCDS: CCDS11679

Canonical transcript exons

ENST00000592554 — 11 exons

Exon	Start	End
ENSE00002278784	68600263	68601367
ENSE00002898480	68535116	68537741
ENSE00003464311	68541985	68542165
ENSE00003479862	68555559	68555743
ENSE00003492039	68543629	68543721
ENSE00003522622	68539885	68539966
ENSE00003600852	68542694	68542809
ENSE00003606049	68539337	68539396
ENSE00003654069	68554777	68554827
ENSE00003662558	68551873	68551951
ENSE00003669476	68540849	68540958

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.54.

FANTOM5 (CAGE): breadth broad, TPM avg 10.0152 / max 385.6868, expressed in 820 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167757	5.5495	641
167750	1.3242	538
167754	0.9896	320
167755	0.8719	344
167753	0.4772	217
167752	0.3337	167
167751	0.1684	97
167756	0.1452	87
167758	0.1288	73
167759	0.0267	13

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.54	gold quality
smooth muscle tissue	UBERON:0001135	93.92	gold quality
upper lobe of left lung	UBERON:0008952	93.54	gold quality
left testis	UBERON:0004533	92.84	gold quality
right testis	UBERON:0004534	92.79	gold quality
upper lobe of lung	UBERON:0008948	92.71	gold quality
stromal cell of endometrium	CL:0002255	92.47	gold quality
body of uterus	UBERON:0009853	91.91	gold quality
endocervix	UBERON:0000458	91.87	gold quality
metanephros cortex	UBERON:0010533	91.72	gold quality
liver	UBERON:0002107	91.65	gold quality
minor salivary gland	UBERON:0001830	90.07	gold quality
body of stomach	UBERON:0001161	90.01	gold quality
saliva-secreting gland	UBERON:0001044	89.93	gold quality
testis	UBERON:0000473	89.71	gold quality
right ovary	UBERON:0002118	89.57	gold quality
omental fat pad	UBERON:0010414	89.38	gold quality
peritoneum	UBERON:0002358	89.30	gold quality
vermiform appendix	UBERON:0001154	89.25	gold quality
gall bladder	UBERON:0002110	89.05	gold quality
left ovary	UBERON:0002119	87.96	gold quality
mucosa of stomach	UBERON:0001199	87.66	gold quality
ectocervix	UBERON:0012249	87.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.51	gold quality
left uterine tube	UBERON:0001303	87.46	gold quality
right lobe of thyroid gland	UBERON:0001119	87.35	gold quality
apex of heart	UBERON:0002098	87.35	gold quality
tibial nerve	UBERON:0001323	87.32	gold quality
right lung	UBERON:0002167	87.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting FAM20A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-6832-5P	99.58	64.82	1132

Literature-anchored findings (GeneRIF, showing 21)

• A homozygous nonsense mutation in exon 2 of FAM20A underlies Amelogenesis imperfecta (AI) – disorders of biomineralization resulting from failure of normal enamel formation. (PMID:21549343)
• We identified a homozygous nonsense mutation in exon 2 of FAM20A that was not present in the Single Nucleotide Polymorphism database (dbSNP), the 1000 Genomes database, or the Centre d’Etude du Polymorphisme Humain (CEPH) Diversity Panel. (PMID:21549343)
• Three homozygous mutations in three families, and a compound heterozygous mutation in one family with hypoplastic amelogenesis imperfecta have been identified in FAM20A. (PMID:21990045)
• Myocardial infarction is distinguished by the up-regulation of SOCS3 and FAM20A genes within first days in the vast majority of patients. (PMID:23185530)
• Data indicate that autosomal recessive FAM20A mutations causes nephrocalcinosis and amelogenesis imperfecta. (PMID:23434854)
• we conclude that FAM20A, which has a kinase homology domain and localizes to the Golgi, is a putative Golgi kinase that plays a significant role in the regulation of biomineralization processes. (PMID:23468644)
• the first duplication in FAM20A and the fifth independent mutation associated with gingival hyperplasia and dental anomalies, is reported. (PMID:23697977)
• study identified 3 novel FAM20A mutations that caused autosomal-recessive amelogenesis imperfecta with delayed and arrested tooth eruption; conclude that FAM20A is likely a secretory pathway kinase and that loss-of-function mutations cause pathology where its phosphorylations are necessary for normal development or homeostasis (PMID:24196488)
• our findings support the suggestion that enamel-renal and AIGFSs are actually the same entity with different manifestations, associated with FAM20A mutations. (PMID:24259279)
• Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro. (PMID:25789606)
• three patients with homozygous or compound heterozygous mutations in FAM20A and findings that extend the phenotypic spectrum of this disorder, showing that protein truncation is associated with greater clinical severity. (PMID:28298625)
• Recessive FAM20A mutations can cause nephrocalcinosis in addition to the oral phenotype (PMID:29439260)
• Physicochemical analysis of human pulpal mineralization secondary to FAM20A mutations. (PMID:29745815)
• Mutations in LAMB3 and FAM20A were found in 3 Turkish families with Amelogenesis imperfecta (PMID:30120606)
• Here we report the largest series of patients with Enamel renal syndrome in a same population, and describe, for the first time, a founder mutation for FAM20A. (PMID:30394349)
• Whole exome sequencing (WES) identified that Pt-1 was heterozygous for FAM20A, c.758A > G (p.Tyr253Cys), inherited from her father. The mutation on maternal allele was not detected by WES. Pt-2 possessed compound heterozygous mutations, c.1248dupG (p.Phe417Valfs*7); c.1081C > T (p.Arg361Cys) in FAM20A. (PMID:32246227)
• Two new families with enamel renal syndrome: A novel FAM20A gene mutation and review of literature. (PMID:32835847)
• Deep dental phenotyping and a novel FAM20A variant in patients with amelogenesis imperfecta type IG. (PMID:36650945)
• FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome. (PMID:37159186)
• FAM20A is a golgi-localized Type II transmembrane protein. (PMID:38499693)
• FAM20A-Associated Amelogenesis Imperfecta: Gene Variants with Functional Verification and Histological Features. (PMID:38546520)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam20a	ENSDARG00000079486
		ENSDARG00000111526
mus_musculus	Fam20a	ENSMUSG00000020614
rattus_norvegicus	Fam20a	ENSRNOG00000003969
drosophila_melanogaster	CG31145	FBGN0051145
caenorhabditis_elegans		WBGENE00010356

Paralogs (2): FAM20B (ENSG00000116199), FAM20C (ENSG00000177706)

Protein

Protein identifiers

Pseudokinase FAM20A — Q96MK3 (reviewed: Q96MK3)

All UniProt accessions (5): Q96MK3, K7EIV7, K7EQL5, L8B8N7, Q71MG5

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with FAM20C; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C.

Subcellular location. Secreted. Golgi apparatus. Endoplasmic reticulum.

Tissue specificity. Highly expressed in lung and liver. Intermediate levels in thymus and ovary.

Post-translational modifications. N-glycosylated.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FAM20 family.

RefSeq proteins (2): NP_001230675, NP_060035* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009581	FAM20_C	Domain
IPR024869	FAM20	Family

Pfam: PF06702

UniProt features (65 total): helix 22, strand 16, turn 7, sequence variant 6, glycosylation site 5, disulfide bond 4, signal peptide 1, chain 1, mutagenesis site 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5WRR	X-RAY DIFFRACTION	2.51
5WRS	X-RAY DIFFRACTION	2.75
5YH3	X-RAY DIFFRACTION	3.3
5YH2	X-RAY DIFFRACTION	3.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MK3-F1	86.10	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 319–323, 378–452, 453–512, 314–330

Glycosylation sites (5): 70, 145, 287, 388, 538

Mutagenesis-validated functional residues (1):

Position	Phenotype
258	able to hydrolyze atp and display some protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 214 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_TOOTH_MINERALIZATION, GOMF_KINASE_ACTIVATOR_ACTIVITY, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ENAMEL_MINERALIZATION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, TGANTCA_AP1_C, GOBP_AMELOGENESIS, BROWN_MYELOID_CELL_DEVELOPMENT_DN, GFI1_01, RYTTCCTG_ETS2_B, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_ODONTOGENESIS_OF_DENTIN_CONTAINING_TOOTH

GO Biological Process (6): positive regulation of protein phosphorylation (GO:0001934), response to bacterium (GO:0009617), biomineral tissue development (GO:0031214), tooth eruption (GO:0044691), calcium ion homeostasis (GO:0055074), enamel mineralization (GO:0070166)

GO Molecular Function (5): protein serine/threonine kinase activator activity (GO:0043539), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP binding (GO:0005524), metal ion binding (GO:0046872)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
response to other organism	1
tissue development	1
animal organ development	1
odontogenesis	1
anatomical structure development	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
tooth mineralization	1
amelogenesis	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
intracellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM20A	FAM20C	Q8IXL6	801
FAM20A	SACK1H	Q6ZRV2	744
FAM20A	WDR72	Q3MJ13	709
FAM20A	ENAM	Q9NRM1	694
FAM20A	ODAPH	Q17RF5	665
FAM20A	GASK1A	Q9UFP1	657
FAM20A	AMBN	Q9NP70	621
FAM20A	FJX1	Q86VR8	621
FAM20A	AMELX	Q99217	608
FAM20A	AMTN	Q6UX39	598
FAM20A	ACP4	Q9BZG2	588
FAM20A	LAMB3	Q13751	584
FAM20A	PRSS23	O95084	553
FAM20A	CNNM4	Q6P4Q7	547
FAM20A	MMP20	O60882	545

IntAct

11 interactions, top by confidence:

A	B	Type	Score
FAM20C	FAM20A	psi-mi:“MI:0407”(direct interaction)	0.610
FAM20A	FAM20C	psi-mi:“MI:0915”(physical association)	0.610
	FAM20A	psi-mi:“MI:0407”(direct interaction)	0.560
	FAM20A	psi-mi:“MI:0882”(atpase reaction)	0.560
FAM20A	SPP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ENAM	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AMTN	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AMBN	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FAM20A	FAM20A	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): FAM20A (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ3, A2XFP3, A2XFT5, A2XFT6, B8AIZ4, C7J0P3, O04536, O48684, O88829, P08037, P15291, P15535, Q02527, Q09327, Q0V7R1, Q0WV13, Q10470, Q10MK2, Q10MQ0, Q16842, Q3UHH8, Q4G148, Q5CAZ6, Q5K027, Q5MJS3, Q5SP46, Q5ZKI6, Q68G12, Q6DE37, Q6GX83, Q6H765, Q6KB58, Q701R2, Q70D51, Q810K9, Q8CID3, Q8GWT1, Q8IXL6, Q8RXE1, Q92184

Diamond homologs: A4VCL2, O75063, Q5MJS3, Q5RH51, Q8CID3, Q8IXL6, Q8VCS3, Q95T10, Q96MK3, Q9XTW2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

364 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	19
Uncertain significance	164
Likely benign	83
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029473	NM_017565.4(FAM20A):c.915_918del (p.Phe305fs)	Pathogenic
1074068	NM_017565.4(FAM20A):c.1371del (p.Thr459fs)	Pathogenic
1076354	NC_000017.10:g.(?66508520)(66533875_?)del	Pathogenic
1240402	NM_017565.4(FAM20A):c.111_145del (p.Glu39fs)	Pathogenic
1322863	NM_017565.4(FAM20A):c.349_367del (p.Leu117fs)	Pathogenic
139648	NM_017565.4(FAM20A):c.720-2A>G	Pathogenic
139649	NM_017565.4(FAM20A):c.1432C>T (p.Arg478Ter)	Pathogenic
139650	NM_017565.4(FAM20A):c.612del (p.Leu205fs)	Pathogenic
1691422	NM_017565.4(FAM20A):c.1109+3_1109+7delinsTGGTC	Pathogenic
1691825	NC_000017.11:g.68534268_68541798del	Pathogenic
1696930	NM_017565.4(FAM20A):c.1447del (p.Glu483fs)	Pathogenic
2424527	NC_000017.10:g.(?66508520)(66548013_?)del	Pathogenic
2723208	NM_017565.4(FAM20A):c.907_908del (p.Ser303fs)	Pathogenic
2779881	NM_017565.4(FAM20A):c.1309C>T (p.Arg437Ter)	Pathogenic
30879	NM_017565.4(FAM20A):c.406C>T (p.Arg136Ter)	Pathogenic
3242586	NM_017565.4(FAM20A):c.188dup (p.Asp63fs)	Pathogenic
35475	NM_017565.4(FAM20A):c.34_35del (p.Leu12fs)	Pathogenic
35476	NM_017565.4(FAM20A):c.813-2A>G	Pathogenic
35477	NM_017565.4(FAM20A):c.1175_1179del (p.Arg392fs)	Pathogenic
35478	NM_017565.4(FAM20A):c.590-2A>G	Pathogenic
35479	NM_017565.4(FAM20A):c.826C>T (p.Arg276Ter)	Pathogenic
3582760	NM_017565.4(FAM20A):c.727C>T (p.Arg243Ter)	Pathogenic
3582770	NM_017565.4(FAM20A):c.466C>T (p.Arg156Ter)	Pathogenic
3667850	NM_017565.4(FAM20A):c.719+1G>T	Pathogenic
3682624	NM_017565.4(FAM20A):c.343_362del (p.Ser115fs)	Pathogenic
4694384	NM_017565.4(FAM20A):c.1310del (p.Arg437fs)	Pathogenic
4845821	NM_017565.4(FAM20A):c.1481_1482dup (p.Leu495fs)	Pathogenic
1066256	NM_017565.4(FAM20A):c.404+2T>G	Likely pathogenic
1677640	NM_001276290.1(PRKAR1A):c.989C>G (p.Ser330Ter)	Likely pathogenic
1691423	NM_017565.4(FAM20A):c.1231C>T (p.Arg411Trp)	Likely pathogenic

SpliceAI

2277 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68539335:A:AC	donor_gain	1.0000
17:68539336:C:CC	donor_gain	1.0000
17:68539336:CATG:C	donor_gain	1.0000
17:68539396:CCTAG:C	acceptor_loss	1.0000
17:68539397:C:CC	acceptor_gain	1.0000
17:68539398:T:A	acceptor_loss	1.0000
17:68539879:GCTCA:G	donor_loss	1.0000
17:68539880:CTCAC:C	donor_loss	1.0000
17:68539881:TCA:T	donor_loss	1.0000
17:68539882:CACCC:C	donor_loss	1.0000
17:68539883:AC:A	donor_gain	1.0000
17:68539884:C:CA	donor_loss	1.0000
17:68539884:CC:C	donor_gain	1.0000
17:68539884:CCCT:C	donor_gain	1.0000
17:68540844:CCTA:C	donor_loss	1.0000
17:68540845:CTA:C	donor_loss	1.0000
17:68540846:TA:T	donor_loss	1.0000
17:68540848:C:CA	donor_loss	1.0000
17:68541983:A:AC	donor_gain	1.0000
17:68541984:C:CC	donor_gain	1.0000
17:68541984:CT:C	donor_gain	1.0000
17:68541984:CTCCT:C	donor_gain	1.0000
17:68542166:C:CC	acceptor_gain	1.0000
17:68551867:ACTT:A	donor_loss	1.0000
17:68551868:CTTA:C	donor_loss	1.0000
17:68551869:TTA:T	donor_loss	1.0000
17:68551870:TAC:T	donor_loss	1.0000
17:68551872:C:CG	donor_loss	1.0000
17:68551947:CACAA:C	acceptor_gain	1.0000
17:68551949:CAA:C	acceptor_gain	1.0000

AlphaMissense

3538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:68539897:T:A	D430V	1.000
17:68542152:G:C	C314W	1.000
17:68551881:T:A	K237N	1.000
17:68551881:T:G	K237N	1.000
17:68539896:G:C	D430E	0.999
17:68539896:G:T	D430E	0.999
17:68539897:T:G	D430A	0.999
17:68539898:C:G	D430H	0.999
17:68539954:C:G	R411P	0.999
17:68539957:T:A	D410V	0.999
17:68539957:T:G	D410A	0.999
17:68539962:A:C	N408K	0.999
17:68539962:A:T	N408K	0.999
17:68540955:C:A	W371C	0.999
17:68540955:C:G	W371C	0.999
17:68542104:A:C	C330W	0.999
17:68542105:C:G	C330S	0.999
17:68542105:C:T	C330Y	0.999
17:68542106:A:G	C330R	0.999
17:68542106:A:T	C330S	0.999
17:68542125:G:C	C323W	0.999
17:68542126:C:G	C323S	0.999
17:68542126:C:T	C323Y	0.999
17:68542127:A:G	C323R	0.999
17:68542127:A:T	C323S	0.999
17:68542137:A:C	C319W	0.999
17:68542138:C:G	C319S	0.999
17:68542139:A:G	C319R	0.999
17:68542139:A:T	C319S	0.999
17:68542153:C:A	C314F	0.999

dbSNP variants (sampled 300 via entrez): RS1000021438 (17:68591766 A>C), RS1000050449 (17:68562476 G>T), RS1000180879 (17:68549251 T>C), RS1000185319 (17:68549443 G>A), RS1000279542 (17:68553096 A>G), RS1000383351 (17:68558608 G>C), RS1000444075 (17:68559102 C>T), RS1000474694 (17:68591603 G>A,C), RS1000476806 (17:68558827 T>C,G), RS1000548825 (17:68556747 G>A), RS1000570912 (17:68550761 T>G), RS1000638090 (17:68602174 G>C), RS1000644491 (17:68594096 G>C), RS1000654690 (17:68563905 GCT>G), RS1000662078 (17:68556523 G>A)

Disease associations

OMIM: gene MIM:611062 | disease phenotypes: MIM:204690, MIM:614253, MIM:160980, MIM:101800, MIM:255960, MIM:610489

GenCC curated gene-disease

Disease	Classification	Inheritance
amelogenesis imperfecta type 1G	Definitive	Autosomal recessive

Mondo (6): amelogenesis imperfecta type 1G (MONDO:0008771), Carney complex, type 1 (MONDO:0008057), hereditary neoplastic syndrome (MONDO:0015356), Acrodysostosis 1 with or without hormone resistance (MONDO:0007044), familial atrial myxoma (MONDO:0009719), pigmented nodular adrenocortical disease, primary, 1 (MONDO:0012509)

Orphanet (7): Enamel-renal syndrome (Orphanet:1031), Amelogenesis imperfecta-gingival hyperplasia syndrome (Orphanet:171836), Carney complex (Orphanet:1359), Inherited cancer-predisposing syndrome (Orphanet:140162), OBSOLETE: Primary pigmented nodular adrenocortical disease (Orphanet:189439), OBSOLETE: Acrodysostosis with multiple hormone resistance (Orphanet:280651), Familial atrial myxoma (Orphanet:615)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000103	Polyuria
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000158	Macroglossia
HP:0000169	Gingival fibromatosis
HP:0000212	Gingival overgrowth
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000696	Delayed eruption of permanent teeth
HP:0000704	Periodontitis
HP:0000705	Amelogenesis imperfecta
HP:0000805	Enuresis
HP:0001548	Overgrowth
HP:0003127	Hypocalciuria
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003771	Pulp calcification
HP:0004727	Impaired renal concentrating ability
HP:0006286	Yellow-brown discoloration of the teeth
HP:0006302	Dagger-shaped pulp calcifications
HP:0009102	Anterior open-bite malocclusion
HP:0009804	Tooth agenesis
HP:0011069	Supernumerary tooth
HP:0011073	Abnormality of dental color
HP:0011079	Impacted tooth
HP:0012101	Decreased serum creatinine
HP:0012365	Hypophosphaturia
HP:0012405	Hypocitraturia
HP:0031428	Increased circulating osteocalcin level

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_663	Blood protein levels	2.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C538241	Amelogenesis imperfecta nephrocalcinosis (supp.)
C538262	Atrial myxoma, familial (supp.)
C566469	Pigmented Nodular Adrenocortical Disease, Primary, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
Aflatoxin B1	increases methylation, decreases expression, decreases methylation	4
Acetaminophen	decreases expression	3
Tetrachlorodibenzodioxin	increases expression	3
entinostat	affects cotreatment, increases expression	2
Nickel	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
titanium dioxide	increases methylation	1
testosterone undecanoate	affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Leflunomide	increases expression	1
Arsenicals	increases expression	1
Dexamethasone	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

32 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01536717	PHASE4	SUSPENDED	Comparison of the Local Anaesthetics Articaine and Bupivacaine in Treatment of Acute Sternum Pain After Heart Surgery
NCT07285421	Not specified	NOT_YET_RECRUITING	Renal and Vascular Phenotypic Characterization of Patients With Enamel Renal Syndrome Due to a Pathogenic Variant of the FAM20A Gene and Pathophysiological Study of Ectopic Calcifications
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
NCT06726642	Not specified	RECRUITING	CfDNA in Hereditary And High-risk Malignancies 2
NCT06914726	Not specified	ENROLLING_BY_INVITATION	Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes
NCT06927947	Not specified	RECRUITING	Navigation Interventions to Improve Cascade Genetic Testing Among Relatives of Patients With Hereditary Cancer Syndromes
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT07052266	Not specified	RECRUITING	Trial of Combined Obstetric Carrier Screening and Hereditary Cancer Screening
NCT07195071	Not specified	RECRUITING	Feasibility Trial of Combination of Obstetrical Carrier Screening and Hereditary Cancer Screening
NCT07378423	Not specified	RECRUITING	Questionnaire on Congenital Cancer Signs Through Self-Assessment
NCT07381985	Not specified	ENROLLING_BY_INVITATION	Strategy for Management of Patients With Hereditary Cancer Syndromes (HCS) in a Rural Environment
NCT07542405	Not specified	NOT_YET_RECRUITING	A Web-Based Program (Kindred) to Improve the Understanding of Genetic Cancer Risk and Cancer Genetic Testing in African American Families
NCT00668291	Not specified	COMPLETED	Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the CARNEY Complex (CNC)