ODAPH

Chr 4AR

odontogenesis associated phosphoprotein

Also known as: AI2A4, C4orf26

NCBI Gene: 152816 ENSG00000174792 OMIM: 614829

ODAPH encodes an extracellular matrix acidic phosphoprotein that promotes nucleation of hydroxyapatite during enamel mineralization. Mutations cause autosomal recessive amelogenesis imperfecta type IIA4, characterized by hypomineralized tooth enamel. The gene shows low constraint to loss-of-function variants (pLI 0.05, LOEUF 1.67), consistent with its recessive inheritance pattern and primary effect on dental development rather than essential cellular functions.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.671 OMIM phenotype

Clinical Summary— ODAPH

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Population Constraint (gnomAD)

Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 1 VUS of 25 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.050

Z-score 0.66

OE 0.61 (0.24–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.06 (0.90–1.25)

102 obs / 96.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.24–1.67)

0≤0.351.4

Missense OE?1.06 (0.90–1.25)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 2 / 3.3Missense obs/exp: 102 / 96.1Syn Z: -0.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateODAPH-related amyelogenesis imperfectaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.84top 10%

GOF

0.4283th %ile

LOF

0.1697th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic4

VUS1

Likely Benign5

Benign8

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	4	0	0	0	4
VUS	0	1	0	0	1
Likely Benign	0	2	1	2	5
Benign	0	3	5	0	8
Total	7	6	6	2	21

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap ODAPH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →