AMER1

Chr XXLD

APC membrane recruitment protein 1

Also known as: FAM123B, OSCS, WTX

The AMER1 protein regulates canonical Wnt signaling by binding phosphatidylinositol 4,5-bisphosphate and interacting with components of the beta-catenin destruction complex. Mutations cause osteopathia striata with cranial sclerosis, a skeletal dysplasia with X-linked dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.37).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLDLOEUF 0.371 OMIM phenotype
Clinical SummaryAMER1
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Gene-Disease Validity (ClinGen)
osteopathia striata with cranial sclerosis · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.854
Z-score 4.06
OE 0.18 (0.090.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.57Z-score
OE missense 1.08 (1.001.16)
474 obs / 440.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.18 (0.090.37)
00.351.4
Missense OE1.08 (1.001.16)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 5 / 28.3Missense obs/exp: 474 / 440.4Syn Z: -1.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAMER1-related osteopathia striata with cranial sclerosisLOFmonoallelic_X_heterozygous
DN
0.3694th %ile
GOF
0.4283th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.37

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AMER1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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