ODAPH

Summary

ODAPH (odontogenesis associated phosphoprotein, HGNC:26300) is a protein-coding gene on chromosome 4q21.1, encoding Odontogenesis associated phosphoprotein (Q17RF5). May promote nucleation of hydroxyapatite.

Dental enamel forms the outer cap of teeth and is the hardest substance found in vertebrates. This gene is thought to encode an extracellular matrix acidic phosphoprotein that has a function in enamel mineralization during amelogenesis. Mutations in this gene are associated with recessive hypomineralized amelogenesis imperfecta.

Source: NCBI Gene 152816 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelogenesis imperfecta hypomaturation type 2A4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 24 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_178497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26300
Approved symbol	ODAPH
Name	odontogenesis associated phosphoprotein
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23657, AI2A4
Ensembl gene	ENSG00000174792
Ensembl biotype	protein_coding
OMIM	614829
Entrez	152816

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000311623, ENST00000435974, ENST00000511093, ENST00000514064, ENST00000616557

RefSeq mRNA: 3 — MANE Select: NM_178497 NM_001206981, NM_001257072, NM_178497

CCDS: CCDS3569, CCDS56334, CCDS75142

Canonical transcript exons

ENST00000311623 — 2 exons

Exon	Start	End
ENSE00000000344	75556066	75556149
ENSE00001762032	75564114	75564817

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 77.92.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0045 / max 2324.3356, expressed in 215 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48301	3.0045	215

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.92	gold quality
buccal mucosa cell	CL:0002336	69.50	silver quality
placenta	UBERON:0001987	68.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.48	gold quality
gastrocnemius	UBERON:0001388	62.27	gold quality
spinal cord	UBERON:0002240	61.37	gold quality
muscle of leg	UBERON:0001383	60.32	gold quality
mucosa of stomach	UBERON:0001199	59.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.04	gold quality
gingiva	UBERON:0001828	57.55	gold quality
ileal mucosa	UBERON:0000331	57.47	silver quality
tibialis anterior	UBERON:0001385	57.37	silver quality
substantia nigra	UBERON:0002038	56.83	gold quality
amygdala	UBERON:0001876	56.56	gold quality
nucleus accumbens	UBERON:0001882	56.04	gold quality
putamen	UBERON:0001874	55.93	gold quality
midbrain	UBERON:0001891	54.87	gold quality
cerebellar hemisphere	UBERON:0002245	54.82	gold quality
right uterine tube	UBERON:0001302	54.74	gold quality
tibial nerve	UBERON:0001323	54.54	gold quality
cerebellar cortex	UBERON:0002129	54.52	gold quality
hypothalamus	UBERON:0001898	54.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
right frontal lobe	UBERON:0002810	54.04	gold quality
caudate nucleus	UBERON:0001873	54.01	gold quality
gingival epithelium	UBERON:0001949	54.00	silver quality
kidney epithelium	UBERON:0004819	53.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting ODAPH, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 1)

• Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (PMID:22901946)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Odaph	ENSMUSG00000096035
rattus_norvegicus	Odaph	ENSRNOG00000079983

Protein

Protein identifiers

Odontogenesis associated phosphoprotein — Q17RF5 (reviewed: Q17RF5)

All UniProt accessions (3): Q17RF5, A0A087WV33, D6RFW7

UniProt curated annotations — full annotation on UniProt →

Function. May promote nucleation of hydroxyapatite.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in placenta.

Disease relevance. Amelogenesis imperfecta, hypomaturation type, 2A4 (AI2A4) [MIM:614832] A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q17RF5-1	1	yes
Q17RF5-2	2

RefSeq proteins (3): NP_001193910, NP_001244001, NP_848592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031706	ODAPH	Family

Pfam: PF15848

UniProt features (6 total): sequence variant 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q17RF5-F1	61.64	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): RACCACAR_AML_Q6, GOBP_TOOTH_MINERALIZATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ENAMEL_MINERALIZATION, OCT1_07, TGANTCA_AP1_C, GOBP_AMELOGENESIS, RYTTCCTG_ETS2_B, SENESE_HDAC1_TARGETS_UP, GOBP_ODONTOGENESIS_OF_DENTIN_CONTAINING_TOOTH, HAND1E47_01, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, COWLING_MYCN_TARGETS, chr4q21, GOBP_ODONTOGENESIS

GO Biological Process (2): positive regulation of biomineral tissue development (GO:0070169), positive regulation of enamel mineralization (GO:0070175)

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biomineral tissue development	1
positive regulation of developmental process	1
regulation of biomineral tissue development	1
enamel mineralization	1
positive regulation of tooth mineralization	1
regulation of enamel mineralization	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ODAPH	WDR72	Q3MJ13	813
ODAPH	SACK1H	Q6ZRV2	773
ODAPH	ENAM	Q9NRM1	773
ODAPH	MMP20	O60882	728
ODAPH	AMBN	Q9NP70	720
ODAPH	AMTN	Q6UX39	720
ODAPH	AMELX	Q99217	720
ODAPH	SLC24A4	Q8NFF2	696
ODAPH	GPR68	Q15743	683
ODAPH	FAM20A	Q96MK3	665
ODAPH	ODAM	A1E959	653
ODAPH	KLK4	Q9Y5K2	637
ODAPH	ACP4	Q9BZG2	620
ODAPH	MMP25	Q9NPA2	606
ODAPH	LAMB3	Q13751	602

IntAct

16 interactions, top by confidence:

A	B	Type	Score
ODAPH	MDFI	psi-mi:“MI:0915”(physical association)	0.720
ODAPH	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	ODAPH	psi-mi:“MI:0915”(physical association)	0.560
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
ODAPH	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ODAPH	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
ODAPH	LCN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (75): C4orf26 (Two-hybrid), NUDT8 (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), ANKRD50 (Affinity Capture-MS), JMJD4 (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), FBN1 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), NPHP3 (Affinity Capture-MS), GPC3 (Affinity Capture-MS), PMPCB (Affinity Capture-MS), PMPCA (Affinity Capture-MS), HAPLN3 (Affinity Capture-MS), TOP3A (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K6Z9, A0A1D0BN92, A0A411D538, A1YQ92, B3A0Q4, D5L5Q8, H2A0M0, K9N4Q4, O08546, O15946, O35979, O35985, O36359, P06796, P07498, P0DMD3, P0DMD4, P11841, P13432, P15450, P18897, P34468, P54684, P55796, P79139, P81058, P81059, P83055, P83474, P86735, Q01493, Q09283, Q17RF5, Q28441, Q28451, Q28794, Q29135, Q29137, Q61900, Q7T6X1

Diamond homologs: A0A0G2K6Z9, Q17RF5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	1
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
37216	NM_178497.5(ODAPH):c.229C>T (p.Arg77Ter)	Pathogenic
37217	NM_178497.5(ODAPH):c.129C>A (p.Cys43Ter)	Pathogenic
37218	NM_178497.5(ODAPH):c.68-2A>T	Pathogenic
3357780	NM_178497.5(ODAPH):c.68-2A>G	Likely pathogenic
37219	NM_178497.3(C4orf26):c.318G>A	Likely pathogenic
37220	NM_178497.5(ODAPH):c.51_56delinsATGCTGGTTACTGGTA (p.Val18fs)	Likely pathogenic
4813733	NM_178497.5(ODAPH):c.225dup (p.Pro76fs)	Likely pathogenic

SpliceAI

273 predictions. Top by Δscore:

Variant	Effect	Δscore
4:75564109:CACAG:C	acceptor_loss	0.9900
4:75564111:CAGGA:C	acceptor_loss	0.9900
4:75564112:A:AG	acceptor_gain	0.9900
4:75564112:AGG:A	acceptor_loss	0.9900
4:75564113:G:A	acceptor_loss	0.9900
4:75564113:G:GG	acceptor_gain	0.9900
4:75556148:AG:A	donor_loss	0.9700
4:75556149:GG:G	donor_loss	0.9700
4:75556150:GTAAG:G	donor_loss	0.9700
4:75556146:GAAG:G	donor_gain	0.9600
4:75564112:AG:A	acceptor_gain	0.9500
4:75564113:GG:G	acceptor_gain	0.9500
4:75556133:G:GA	donor_gain	0.9200
4:75564113:GGA:G	acceptor_gain	0.9200
4:75558106:GCTCT:G	donor_gain	0.9000
4:75564110:A:AG	acceptor_gain	0.9000
4:75556117:T:A	donor_gain	0.8700
4:75556138:C:G	donor_gain	0.8700
4:75564113:GGAC:G	acceptor_gain	0.8700
4:75564113:GGACA:G	acceptor_gain	0.8700
4:75558150:T:TA	donor_gain	0.8600
4:75558151:A:AA	donor_gain	0.8600
4:75564112:A:C	acceptor_gain	0.8600
4:75564219:TCAC:T	donor_gain	0.8600
4:75558155:ACCT:A	donor_gain	0.8500
4:75563208:A:AG	acceptor_gain	0.8500
4:75563209:G:GG	acceptor_gain	0.8500
4:75563209:GTA:G	acceptor_gain	0.8500
4:75564111:CA:C	acceptor_gain	0.8500
4:75556150:G:GG	donor_gain	0.8400

AlphaMissense

847 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:75564419:A:C	S125R	0.911
4:75564421:C:A	S125R	0.911
4:75564421:C:G	S125R	0.911
4:75564182:T:C	F46L	0.898
4:75564184:T:A	F46L	0.898
4:75564184:T:G	F46L	0.898
4:75564434:A:C	S130R	0.881
4:75564436:C:A	S130R	0.881
4:75564436:C:G	S130R	0.881
4:75564429:A:T	E128V	0.841
4:75564314:T:C	F90L	0.813
4:75564316:C:A	F90L	0.813
4:75564316:C:G	F90L	0.813
4:75564426:C:T	S127F	0.808
4:75564175:C:G	C43W	0.799
4:75564183:T:G	F46C	0.798
4:75564426:C:A	S127Y	0.797
4:75556122:T:C	C14R	0.796
4:75564183:T:C	F46S	0.784
4:75564180:T:C	I45T	0.779
4:75556125:T:A	W15R	0.777
4:75556125:T:C	W15R	0.777
4:75564173:T:C	C43R	0.765
4:75564299:T:C	F85L	0.760
4:75564301:T:A	F85L	0.760
4:75564301:T:G	F85L	0.760
4:75564347:T:C	F101L	0.753
4:75564349:C:A	F101L	0.753
4:75564349:C:G	F101L	0.753
4:75564341:T:C	F99L	0.750

dbSNP variants (sampled 300 via entrez): RS1000094572 (4:75564826 C>T), RS1000288026 (4:75561034 G>A), RS1000490226 (4:75555196 C>T), RS1000519307 (4:75564375 A>G), RS1000530658 (4:75561922 T>A,C,G), RS1000536462 (4:75566340 T>A), RS1000688982 (4:75556358 C>G), RS1000731169 (4:75558840 T>C), RS1000794163 (4:75560166 G>A), RS1000998765 (4:75556025 C>A), RS1001320637 (4:75561084 C>A,T), RS1001410377 (4:75561178 C>G,T), RS1001644152 (4:75565425 T>A,C), RS1001654736 (4:75559199 T>C), RS1001662052 (4:75555608 G>A,C,T)

Disease associations

OMIM: gene MIM:614829 | disease phenotypes: MIM:614832

GenCC curated gene-disease

Disease	Classification	Inheritance
amelogenesis imperfecta hypomaturation type 2A4	Strong	Autosomal recessive
amelogenesis imperfecta type 2	Supportive	Autosomal recessive

Mondo (2): amelogenesis imperfecta hypomaturation type 2A4 (MONDO:0013906), amelogenesis imperfecta type 2 (MONDO:0015048)

Orphanet (1): Amelogenesis imperfecta (Orphanet:88661)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000705	Amelogenesis imperfecta
HP:0006285	Enamel hypomineralization
HP:0006297	Enamel hypoplasia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001546_4	Parkinson’s disease (motor and cognition)	5.000000e-06
GCST003160_4	Subjective response to lithium treatment in bipolar disorder	7.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536606	Amelogenesis Imperfecta hypomaturation type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
2-palmitoylglycerol	increases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Diethylhexyl Phthalate	increases expression	1
Diuron	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Zearalenone	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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