ODAPH

protein-coding

odontogenesis associated phosphoprotein

Gene summary

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. [provided by RefSeq, Oct 2012]

Previous symbols:

C4orf26

MANE transcript

NM_178497.5

Inheritance

ClinVar variants

P:8U:2B:4

Top phenotype

Amelogenesis imperfecta, hypomaturation type, IIA4

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr4:75,556,048-75,565,871

External References & Databases

Ensembl (ENSG00000174792)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015048

Submitter: Orphanet

amelogenesis imperfecta hypomaturation type 2A4MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013906

Submitter: G2P

amelogenesis imperfecta hypomaturation type 2A4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013906

Submitter: PanelApp Australia

amelogenesis imperfecta hypomaturation type 2A4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013906

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, hypomaturation type, IIA4AR

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: 22901946

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ODAPH variants in ClinVar

4 Conditions Cataloged

ODAPH-related disorderTotal: 6

Amelogenesis imperfecta hypomaturation type 2A4Total: 6

not providedTotal: 2

not specifiedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178497.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	2 clinvar		4
missense		1 clinvar		1 clinvar	1 clinvar	3
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	3	5	2	3	1	14

Highest pathogenic variant AF is 0.000060719914

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178497.5	RefSeq	NP_848592.2	2	MANE Select
ENST00000311623.9	Ensembl	ENSP00000311307.5	2	MANE Select
NM_001206981.2	RefSeq	NP_001193910.1	3	Standard
NM_001257072.2	RefSeq	NP_001244001.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of biomineral tissue development
positive regulation of enamel mineralization

Molecular Function

protein binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000435974
Coding exons: 3
Length: 9838
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125730
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.215	102	96.1	1.06	0.00000542	1134
Missense (PolyPhen)		9	4.865	1.8499		52
Synonymous	-0.0983	38	37.2	1.02	0.00000218	351
Loss of Function	0.655	2	3.28	0.610	1.40e-7	36

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May promote nucleation of hydroxyapatite. {ECO:0000269|PubMed:22901946}.;

Intolerance Scores

RVIS EVS: 0.97
RVIS percentile EVS: 90.23

Essentials

Essential (gene trap): N