ODAPH

Chr 4AR

odontogenesis associated phosphoprotein

Also known as: AI2A4, C4orf26

NCBI Gene: 152816 ENSG00000174792 UniProt: Q17RF5 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…

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IIA4MIM #614832

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Amelogenesis imperfecta, type IIA4; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in ODAPH?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

287 rare PASS variants

Rare truncating (LoF)

1 in 520

49 rare PASS variants

Rare synonymous (reference)

1 in 1,200

31 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ODAPH; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 580
South Asian	~43k	1 in 190	1 in 1,500
Remaining (unassigned)	~30k	1 in 180	1 in 480
European (Finnish)	~27k	1 in 1,600	1 in 610
Admixed American	~22k	1 in 150	1 in 760
African / African American	~21k	1 in 210	1 in 990
East Asian	~20k	1 in 110	1 in 1,000
Ashkenazi Jewish	~13k	1 in 1,500	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 130	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓