ODAM

Summary

ODAM (odontogenic, ameloblast associated, HGNC:26043) is a protein-coding gene on chromosome 4q13.3, encoding Odontogenic ameloblast-associated protein (A1E959). Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth.

Involved in several processes, including positive regulation of GTPase activity; positive regulation of epithelial cell proliferation involved in wound healing; and positive regulation of macromolecule metabolic process. Located in several cellular components, including extracellular space; mitotic spindle; and nucleoplasm.

Source: NCBI Gene 54959 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_017855

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26043
Approved symbol	ODAM
Name	odontogenic, ameloblast associated
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	APin, FLJ20513
Ensembl gene	ENSG00000109205
Ensembl biotype	protein_coding
OMIM	614843
Entrez	54959

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000396094, ENST00000506248, ENST00000510709, ENST00000510847, ENST00000514097, ENST00000683306, ENST00000877210, ENST00000955828

RefSeq mRNA: 2 — MANE Select: NM_017855 NM_001385579, NM_017855

CCDS: CCDS3536

Canonical transcript exons

ENST00000683306 — 12 exons

Exon	Start	End
ENSE00001400282	70204175	70204576
ENSE00001726002	70196692	70196733
ENSE00001743180	70197924	70198157
ENSE00001764227	70197274	70197321
ENSE00003485888	70201454	70201501
ENSE00003488485	70200497	70200601
ENSE00003500266	70202756	70202917
ENSE00003583619	70202258	70202329
ENSE00003658360	70203156	70203214
ENSE00003679528	70198579	70198626
ENSE00003917545	70196529	70196594
ENSE00003920530	70195725	70195793

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 99.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8733 / max 817.3198, expressed in 137 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47907	0.9479	105
47906	0.6097	76
47904	0.1396	9
47905	0.1250	44
47903	0.0510	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.48	gold quality
saliva-secreting gland	UBERON:0001044	93.08	gold quality
trachea	UBERON:0003126	92.68	gold quality
minor salivary gland	UBERON:0001830	92.46	gold quality
parotid gland	UBERON:0001831	90.58	gold quality
mouth mucosa	UBERON:0003729	88.10	gold quality
nasal cavity mucosa	UBERON:0001826	84.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.48	gold quality
buccal mucosa cell	CL:0002336	76.15	gold quality
body of stomach	UBERON:0001161	75.70	gold quality
right lobe of thyroid gland	UBERON:0001119	75.48	gold quality
left lobe of thyroid gland	UBERON:0001120	75.11	gold quality
gingiva	UBERON:0001828	74.13	gold quality
stomach	UBERON:0000945	73.37	gold quality
thyroid gland	UBERON:0002046	73.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.57	gold quality
fundus of stomach	UBERON:0001160	67.55	gold quality
gingival epithelium	UBERON:0001949	66.65	gold quality
tonsil	UBERON:0002372	66.28	gold quality
vermiform appendix	UBERON:0001154	64.92	gold quality
right lung	UBERON:0002167	64.44	gold quality
pylorus	UBERON:0001166	64.06	gold quality
colonic epithelium	UBERON:0000397	61.84	gold quality
caecum	UBERON:0001153	61.08	gold quality
seminal vesicle	UBERON:0000998	60.61	gold quality
upper lobe of left lung	UBERON:0008952	60.14	gold quality
upper lobe of lung	UBERON:0008948	60.04	gold quality
lung	UBERON:0002048	59.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.15

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CDH1	Activation
ROCK1	Activation

Upstream regulators (CollecTRI, top): ITGB3, RUNX2

miRNA regulators (miRDB)

32 targeting ODAM, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4701-5P	96.45	68.41	1121

Literature-anchored findings (GeneRIF, showing 13)

• Calcifying epithelial odontogenic tumor-associated amyloid consists of a unique and previously undescribed protein that we provisionally designate APin. (PMID:14647039)
• The protein sequences deduced from the cloned cDNA for rat, mouse, pig, and human were aligned together with those obtained from four other mammal genomes. Apin is highly conserved in mammals. (PMID:17647262)
• Data suggest that ODAM is a developmental antigen that has an essential role in tooth maturation and in the pathogenesis of certain odontogenic and other epithelial neoplasms (PMID:18472969)
• Confirmation of the amyloidogenic potential of ODAM has resulted from analyses of four other cases where we found, in addition, a 74-residue segment specified by exon 4. (PMID:18484335)
• The expression of APIN at an early time-point following disruption of periodontal integrity suggests that this protein may be part of the cascade of events leading to the activation of ERM during periodontal healing and regeneration (PMID:20572917)
• We propose that ODAM has diverse functions that vary with protein location in various cell lines. Nuclear ODAM appears to be associated with MMP-20 regulation and tumorigenesis. Additional functions may take place in cytoplasm and extracellular matrix. (PMID:22387195)
• Our studies demonstrate that ectopic ODAM expression in melanoma cell lines suppresses growth and migratory activity in these cells, while eliciting elevated PTEN expression and suppression of AKT activity. (PMID:23648148)
• ODAM induced RhoA activity. ODAM-mediated RhoA signalling resulted in actin filament rearrangement, increased cell adhesion and inhibited the migration/invasion of MCF7 cells. These results suggest that ODAM expression maintains their adhesion, resulting in the prevention of their metastasis via the regulation of RhoA signalling in breast cancer cells. (PMID:26358398)
• Risk of recurrence correlated with cytoplasmic expression of ODAM and pAKT, whereas nuclear expression did not predict recurrence of gastrointestinal stromal tumors. (PMID:27229116)
• The inhibitory effects of ODAM on colorectal cancer cell growth were associated with PTEN elevation and PI3K/AKT signaling inactivation. (PMID:27694004)
• Similar to AMTN, ODAM is able to promote HA nucleation in a dose-dependent manner in SBF, and even outside of its biological context in vitro. (PMID:29745811)
• AMELX and ODAM variations was not different between two populations of schoolchildren with respect to dental fluorosis (DF) severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF (PMID:31838295)
• CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway. (PMID:34634673)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Odam	ENSMUSG00000009580
rattus_norvegicus	Odam	ENSRNOG00000023372

Protein

Protein identifiers

Odontogenic ameloblast-associated protein — A1E959 (reviewed: A1E959)

Alternative names: Apin

All UniProt accessions (4): A1E959, D6RA81, H0Y8T7, H0YA46

UniProt curated annotations — full annotation on UniProt →

Function. Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. May be incorporated in the enamel matrix at the end of mineralization process. Involved in the induction of RHOA activity via interaction with ARHGEF and expression of downstream factors such as ROCK. Plays a role in attachment of the junctional epithelium to the tooth surface.

Subunit / interactions. Interacts (via C-terminus) with ARHGEF5.

Subcellular location. Secreted. Cytoplasm. Nucleus.

Tissue specificity. Expressed in the junctional epithelium of healthy teeth. In periodontitis, absent in the pocket epithelium of the diseased periodontium but is detected in the gingival crevicular fluid.

Post-translational modifications. O-glycosylated.

Miscellaneous. ODAM protein is the unique constituent of calcifying epithelial odontogenic tumors (CEOTs), also known as Pindborg tumors. CEOTs are benign but locally aggressive pathologic entities arising mainly in the mandible and commonly associated with an unerupted or embedded tooth. They are characterized by the presence of squamous-cell proliferation, calcification, and, notably, amyloid deposits.

Similarity. Belongs to the ODAM family.

RefSeq proteins (2): NP_001372508, NP_060325* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026802	Odam	Family

Pfam: PF15424

UniProt features (20 total): glycosylation site 12, sequence variant 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1E959-F1	43.07	0.00

Functional residue map

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

Glycosylation sites (12): 250, 251, 255, 256, 261, 263, 273, 275, 115, 119, 244, 249

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977225	Amyloid fiber formation

MSigDB gene sets: 92 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, chr4q13, GOBP_WOUND_HEALING, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, RICKMAN_HEAD_AND_NECK_CANCER_A, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, GOBP_ODONTOGENESIS_OF_DENTIN_CONTAINING_TOOTH, GOBP_EPITHELIAL_CELL_PROLIFERATION

GO Biological Process (9): positive regulation of protein phosphorylation (GO:0001934), inflammatory response (GO:0006954), positive regulation of gene expression (GO:0010628), biomineral tissue development (GO:0031214), regulation of actin cytoskeleton organization (GO:0032956), odontogenesis of dentin-containing tooth (GO:0042475), positive regulation of GTPase activity (GO:0043547), positive regulation of epithelial cell proliferation involved in wound healing (GO:0060054), response to wounding (GO:0009611)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cell periphery (GO:0071944), mitotic spindle (GO:0072686), supramolecular fiber (GO:0099512)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
defense response	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
tissue development	1
animal organ development	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
odontogenesis	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
wound healing	1
positive regulation of epithelial cell proliferation	1
response to stress	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
spindle	1
supramolecular polymer	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ODAM	AMTN	Q6UX39	963
ODAM	ENAM	Q9NRM1	855
ODAM	AMBN	Q9NP70	780
ODAM	MMP20	O60882	741
ODAM	FDCSP	Q8NFU4	702
ODAM	AMELX	Q99217	695
ODAM	KLK4	Q9Y5K2	666
ODAM	ODAPH	Q17RF5	653
ODAM	ACP4	Q9BZG2	535
ODAM	IBSP	P21815	518
ODAM	TUFT1	Q9NNX1	512
ODAM	PRR27	Q6MZM9	507
ODAM	MEPE	Q9NQ76	503
ODAM	DMP1	Q13316	501
ODAM	EDAR	Q9UNE0	461

IntAct

43 interactions, top by confidence:

A	B	Type	Score
ODAM	FHL2	psi-mi:“MI:0914”(association)	0.560
ODAM	SPATA31A7	psi-mi:“MI:0915”(physical association)	0.560
ODAM	SNRPC	psi-mi:“MI:0915”(physical association)	0.560
ODAM	MED25	psi-mi:“MI:0915”(physical association)	0.560
ODAM	HGS	psi-mi:“MI:0915”(physical association)	0.560
ODAM	ADAM15	psi-mi:“MI:0915”(physical association)	0.560
ODAM	VENTX	psi-mi:“MI:0915”(physical association)	0.560
	ODAM	psi-mi:“MI:0915”(physical association)	0.560
ODAM	SDCBP	psi-mi:“MI:0915”(physical association)	0.560
ODAM	ARID5A	psi-mi:“MI:0915”(physical association)	0.560
POGZ	ODAM	psi-mi:“MI:0915”(physical association)	0.560
ODAM	FHL2	psi-mi:“MI:0915”(physical association)	0.560
ODAM	TOLLIP	psi-mi:“MI:0915”(physical association)	0.550
BRAF	ODAM	psi-mi:“MI:2364”(proximity)	0.470
BRAF	ODAM	psi-mi:“MI:0915”(physical association)	0.470
FBXW7	ODAM	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	ODAM	psi-mi:“MI:2364”(proximity)	0.270
ODAM	PTEN	psi-mi:“MI:2364”(proximity)	0.270
ODAM	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
ODAM	EGFR	psi-mi:“MI:2364”(proximity)	0.270
SPATA31A7	ODAM	psi-mi:“MI:0915”(physical association)	0.000
SNRPC	ODAM	psi-mi:“MI:0915”(physical association)	0.000
POGZ	ODAM	psi-mi:“MI:0915”(physical association)	0.000
	ODAM	psi-mi:“MI:0915”(physical association)	0.000
MED25	ODAM	psi-mi:“MI:0915”(physical association)	0.000
HGS	ODAM	psi-mi:“MI:0915”(physical association)	0.000
ADAM15	ODAM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): ODAM (Two-hybrid), FHL2 (Affinity Capture-MS), NISCH (Affinity Capture-MS), ODAM (Two-hybrid), ODAM (Two-hybrid), SNRPC (Two-hybrid), SDCBP (Two-hybrid), POGZ (Two-hybrid), ADAM15 (Two-hybrid), VENTX (Two-hybrid), HGS (Two-hybrid), ARID5A (Two-hybrid), SPATA31A7 (Two-hybrid), FHL2 (Affinity Capture-MS), ODAM (Reconstituted Complex)

ESM2 similar proteins: A1E959, A1E960, A1YQ91, A1YQ92, A1YQ93, A1YQ94, B3A0S0, B5DRT7, O55189, O62823, P02661, P02662, P02665, P02668, P02669, P02670, P04653, P06796, P10598, P11840, P11841, P18626, P19228, P19442, P33618, P39035, P39037, P42155, P42156, P42157, P50420, P50421, P50422, P50423, P50424, P50425, P63277, P63278, Q003G9, Q27002

Diamond homologs: A1E959, A1E960, A1YQ91, A1YQ92, A1YQ93, A1YQ94, Q003G9, Q3HS83

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1033 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70196595:G:GG	donor_gain	1.0000
4:70198153:GTCAC:G	donor_gain	1.0000
4:70198158:G:GG	donor_gain	1.0000
4:70200489:A:AG	acceptor_gain	1.0000
4:70200490:C:G	acceptor_gain	1.0000
4:70200491:A:AG	acceptor_gain	1.0000
4:70200492:A:G	acceptor_gain	1.0000
4:70200493:GTA:G	acceptor_gain	1.0000
4:70200495:A:AG	acceptor_gain	1.0000
4:70200496:G:A	acceptor_loss	1.0000
4:70200496:G:GA	acceptor_gain	1.0000
4:70200496:GA:G	acceptor_gain	1.0000
4:70200496:GAT:G	acceptor_gain	1.0000
4:70200598:GCAG:G	donor_gain	1.0000
4:70200599:CAGGT:C	donor_loss	1.0000
4:70200600:AGGTA:A	donor_loss	1.0000
4:70200601:GGTAC:G	donor_loss	1.0000
4:70200602:GTA:G	donor_loss	1.0000
4:70200603:T:G	donor_loss	1.0000
4:70202253:TTTA:T	acceptor_loss	1.0000
4:70202254:TTA:T	acceptor_loss	1.0000
4:70202256:A:AG	acceptor_gain	1.0000
4:70202256:A:T	acceptor_loss	1.0000
4:70202257:G:GG	acceptor_gain	1.0000
4:70202257:GGCT:G	acceptor_gain	1.0000
4:70202328:TGGTA:T	donor_loss	1.0000
4:70202331:TAAGA:T	donor_loss	1.0000
4:70202754:A:AG	acceptor_gain	1.0000
4:70202755:G:GG	acceptor_gain	1.0000
4:70196590:CCCCA:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000248637 (4:70195828 G>A), RS1000475535 (4:70201858 C>T), RS1001032897 (4:70204055 T>C), RS1001106339 (4:70203811 G>A,C), RS1002012157 (4:70203427 T>C), RS1002112884 (4:70197221 T>C), RS1002215501 (4:70198361 A>G), RS1002564676 (4:70199924 G>A), RS1002662447 (4:70203705 A>G,T), RS1002801867 (4:70197673 G>A,T), RS1003088059 (4:70193937 C>T), RS1003466522 (4:70194178 A>T), RS1003568351 (4:70198705 C>G), RS1003599304 (4:70198470 T>C), RS1003792339 (4:70195902 A>G)

Disease associations

OMIM: gene MIM:614843 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Azathioprine	decreases expression	1
Cadmium	decreases expression	1
Calcitriol	affects cotreatment, decreases expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Malathion	decreases expression	1
Quercetin	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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