AMER2

Chr 13

APC membrane recruitment protein 2

Also known as: FAM123A

NCBI Gene: 219287 ENSG00000165566 UniProt: Q8N7J2

The protein negatively regulates the canonical Wnt signaling pathway by binding phosphatidylinositol 4,5-bisphosphate and interacting with components of the beta-catenin destruction complex, playing a role in neuroectodermal patterning. Mutations cause autosomal recessive osteopathia striata with cranial sclerosis, a skeletal dysplasia characterized by longitudinal striations in long bones and sclerosis of cranial bones. The gene shows moderate constraint against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Enables phosphatidylinositol-4,5-bisphosphate binding activity. Involved in negative regulation of canonical Wnt signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in AMER2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,067 rare PASS variants

Rare truncating (LoF)

1 in 3,800

70 rare PASS variants

Rare synonymous (reference)

1 in 92

513 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AMER2. 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 80	1 in 4,100
South Asian	~43k	1 in 47	1 in 4,400
Remaining (unassigned)	~30k	1 in 50	1 in 4,700
European (Finnish)	~27k	1 in 140	1 in 3,100
Admixed American	~22k	1 in 58	1 in 2,000
African / African American	~21k	1 in 66	1 in 2,500
East Asian	~20k	1 in 60	≈ 1 in 4,300
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 5,000
Middle Eastern	~2,884	1 in 77	none seen

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓