AMER1

APC membrane recruitment protein 1, the group of APC membrane recruitment proteins

Basic information

Region (hg38): X:64185116-64205708

Previous symbols: [ "FAM123B" ]

Links

ENSG00000184675 ∙ NCBI:139285 ∙ OMIM:300647 ∙ HGNC:26837 ∙ Uniprot:Q5JTC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteopathia striata with cranial sclerosis (Strong), mode of inheritance: XL
• osteopathia striata with cranial sclerosis (Strong), mode of inheritance: XL
• osteopathia striata with cranial sclerosis (Definitive), mode of inheritance: XL
• osteopathia striata with cranial sclerosis (Supportive), mode of inheritance: XL
• osteopathia striata with cranial sclerosis (Strong), mode of inheritance: XL
• osteopathia striata with cranial sclerosis (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteopathia striata with cranial sclerosis	XL	General	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	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	19079258; 20209645; 20950377; 22987541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMER1 gene.

• not provided (278 variants)
• Osteopathia striata with cranial sclerosis (35 variants)
• Inborn genetic diseases (33 variants)
• not specified (22 variants)
• AMER1-related condition (5 variants)
• Cleft palate (1 variants)
• Spinocerebellar ataxia, X-linked (1 variants)
• Myocarditis;Febrile seizure (within the age range of 3 months to 6 years);Macrocephaly;Ventriculomegaly (1 variants)
• Colorectal cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMER1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	45	24	70
missense			123	38	42	203
nonsense	7	1	7			15
start loss						0
frameshift	11	6	6			23
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)						0
splice region	2					2
non coding					2	2
Total	18	7	139	83	69

Variants in AMER1

This is a list of pathogenic ClinVar variants found in the AMER1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-64189879-C-T		Osteopathia striata with cranial sclerosis • AMER1-related disorder	Benign/Likely benign (Dec 25, 2023)
X-64189881-A-G			Uncertain significance (Oct 22, 2020)
X-64189910-G-A			Uncertain significance (Oct 03, 2023)
X-64189912-G-A			Likely benign (Dec 26, 2023)
X-64189918-G-C		Osteopathia striata with cranial sclerosis	Uncertain significance (Nov 12, 2022)
X-64189929-G-A			Benign (May 29, 2022)
X-64189951-C-T			Benign (Dec 13, 2023)
X-64189957-T-C			Benign (Jan 16, 2024)
X-64189959-A-T		Osteopathia striata with cranial sclerosis	Uncertain significance (Aug 08, 2019)
X-64190001-G-A		Osteopathia striata with cranial sclerosis	Uncertain significance (Dec 02, 2022)
X-64190010-C-T			Uncertain significance (Jun 14, 2023)
X-64190013-G-A			Uncertain significance (Jan 24, 2024)
X-64190014-C-T			Benign (Jan 18, 2024)
X-64190016-G-A		not specified	Benign (Dec 18, 2023)
X-64190021-C-G		Osteopathia striata with cranial sclerosis	Uncertain significance (Apr 20, 2021)
X-64190022-T-C			Uncertain significance (Sep 14, 2022)
X-64190039-C-A			Uncertain significance (Jun 10, 2023)
X-64190059-C-T			Likely benign (Aug 08, 2022)
X-64190061-T-A		Colorectal cancer	Pathogenic (-)
X-64190064-C-T			Uncertain significance (Nov 27, 2023)
X-64190071-T-TA			Uncertain significance (Jan 31, 2023)
X-64190072-A-G		Inborn genetic diseases	Uncertain significance (Feb 02, 2022)
X-64190089-G-A			Likely benign (Oct 29, 2023)
X-64190111-C-T			Uncertain significance (Feb 14, 2023)
X-64190112-TG-T			Uncertain significance (Feb 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMER1	protein_coding	protein_coding	ENST00000330258	1	20628

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.854	0.146	125690	2	6	125698	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.569	474	440	1.08	0.0000330	7382
Missense in Polyphen		105	126.38	0.83083		2172
Synonymous	-1.15	181	162	1.11	0.0000114	2325
Loss of Function	4.06	5	28.3	0.177	0.00000266	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000112	0.000112
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000738	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000497	0.0000352
Middle Eastern	0.0000738	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex. Acts both as a positive and negative regulator of the Wnt signaling pathway, depending on the context: acts as a positive regulator by promoting LRP6 phosphorylation. Also acts as a negative regulator by acting as a scaffold protein for the beta- catenin destruction complex and promoting stabilization of Axin at the cell membrane. Promotes CTNNB1 ubiquitination and degradation. Involved in kidney development. {ECO:0000269|PubMed:17510365, ECO:0000269|PubMed:17925383, ECO:0000269|PubMed:19416806, ECO:0000269|PubMed:21304492, ECO:0000269|PubMed:21498506}.
• Pathway: Degradation of beta-catenin by the destruction complex;Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;Disassembly of the destruction complex and recruitment of AXIN to the membrane;Beta-catenin phosphorylation cascade;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.0852

Intolerance Scores

• rvis_EVS: -0.39
• rvis_percentile_EVS: 27.03

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.734
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Amer1
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: amer1
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: Wnt signaling pathway;positive regulation of protein ubiquitination;bone development;adipose tissue development;regulation of canonical Wnt signaling pathway;mesenchymal cell differentiation involved in kidney development;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of cellular protein catabolic process;beta-catenin destruction complex assembly;beta-catenin destruction complex disassembly
• Cellular component: cytosol;plasma membrane;nuclear body;intracellular membrane-bounded organelle
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;beta-catenin binding;beta-catenin destruction complex binding