AMN

amnion associated transmembrane protein

Basic information

Region (hg38): 14:102922663-102933596

Links

ENSG00000166126 ∙ NCBI:81693 ∙ OMIM:605799 ∙ HGNC:14604 ∙ Uniprot:Q9BXJ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Imerslund-Grasbeck syndrome (Supportive), mode of inheritance: AR
• Imerslund-Grasbeck syndrome type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Imerslund-Grasbeck syndrome 2	AR	Gastrointestinal	Early diagnosis is beneficial, as early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality	Gastrointestinal; Hematologic; Renal	12590260; 17114957; 17285242; 18181028; 22078000; 22854512; 22631584

ClinVar

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

• Imerslund-Grasbeck syndrome (23 variants)
• Imerslund-Grasbeck syndrome type 2 (5 variants)
• Imerslund-Grasbeck syndrome type 1 (2 variants)
• not provided (1 variants)
• Cobalamin deficiency;Megaloblastic anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMN 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				196	1	197
missense		1	74	6		81
nonsense	9	1				10
start loss						0
frameshift	16	2	3			21
inframe indel			2	1	1	4
splice donor/acceptor (+/-2bp)	1	14				15
splice region			8	40		48
non coding	1	1	3	137	18	160
Total	27	19	82	340	20

Highest pathogenic variant AF is 0.000125

Variants in AMN

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

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

Position	Type	Phenotype	Significance	ClinVar
14-102922666-G-C			Benign (Jul 15, 2018)
14-102922695-G-C		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
14-102922699-TG-T		Imerslund-Grasbeck syndrome type 2 • Imerslund-Grasbeck syndrome	Pathogenic (Jan 18, 2024)
14-102922709-C-A		Imerslund-Grasbeck syndrome	Likely benign (Jan 15, 2024)
14-102922709-C-T		Imerslund-Grasbeck syndrome	Likely benign (Oct 18, 2023)
14-102922712-G-T		Imerslund-Grasbeck syndrome	Likely benign (Jul 13, 2023)
14-102922722-C-T		Imerslund-Grasbeck syndrome	Pathogenic (Jan 24, 2024)
14-102922722-CA-C		Imerslund-Grasbeck syndrome type 2	Pathogenic (May 19, 2020)
14-102922731-G-T		Imerslund-Grasbeck syndrome	Uncertain significance (Apr 22, 2022)
14-102922732-G-T		Imerslund-Grasbeck syndrome	Likely pathogenic (-)
14-102922738-C-T		Imerslund-Grasbeck syndrome	Likely benign (Jul 19, 2023)
14-102922739-G-A		Imerslund-Grasbeck syndrome	Likely benign (Aug 12, 2021)
14-102922740-G-A		Imerslund-Grasbeck syndrome	Likely benign (Nov 20, 2023)
14-102922741-G-A		Imerslund-Grasbeck syndrome	Likely benign (Nov 23, 2022)
14-102922742-A-G		Imerslund-Grasbeck syndrome	Likely benign (May 13, 2023)
14-102922746-C-T		Imerslund-Grasbeck syndrome	Likely benign (Sep 26, 2023)
14-102922746-CACCGGTGCGGGCCCGGACGGT-C		Imerslund-Grasbeck syndrome	Likely benign (Sep 27, 2023)
14-102922747-A-G		Imerslund-Grasbeck syndrome	Likely benign (Nov 21, 2023)
14-102922748-C-G		Imerslund-Grasbeck syndrome	Likely benign (Jun 25, 2023)
14-102922748-C-T		Imerslund-Grasbeck syndrome	Likely benign (Sep 24, 2023)
14-102922749-C-T		Imerslund-Grasbeck syndrome	Likely benign (Aug 29, 2023)
14-102922877-C-T			Benign (Jul 31, 2018)
14-102923017-T-C			Likely benign (Sep 21, 2020)
14-102923691-C-T		Imerslund-Grasbeck syndrome	Likely benign (Apr 20, 2023)
14-102923696-T-C		Imerslund-Grasbeck syndrome	Likely benign (Nov 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMN	protein_coding	protein_coding	ENST00000299155	12	10941

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000265	0.985	125471	0	37	125508	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.606	230	257	0.894	0.0000126	2784
Missense in Polyphen		65	66.067	0.98385		775
Synonymous	-0.756	134	123	1.09	0.00000652	1017
Loss of Function	2.17	9	19.3	0.467	8.29e-7	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000931	0.0000905
Ashkenazi Jewish	0.000100	0.0000995
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000199	0.000176
Middle Eastern	0.000110	0.000109
South Asian	0.000362	0.000359
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Necessary for efficient absorption of vitamin B12 (PubMed:12590260, PubMed:14576052). Required for normal CUBN- mediated protein transport in the kidney. May direct the production of trunk mesoderm during development by modulating a bone morphogenetic protein (BMP) signaling pathway in the underlying visceral endoderm (By similarity). {ECO:0000250|UniProtKB:Q99JB7, ECO:0000269|PubMed:14576052, ECO:0000305|PubMed:12590260}.
• Disease: DISEASE: Recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:261100]: Due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected. {ECO:0000269|PubMed:12590260, ECO:0000269|PubMed:22631584}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HDL clearance;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Plasma lipoprotein clearance;Transport of small molecules;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Plasma lipoprotein assembly, remodeling, and clearance (Consensus)

Haploinsufficiency Scores

• pHI: 0.0807
• hipred: N
• hipred_score: 0.329
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.208

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Amn
• Phenotype: cellular phenotype; skeleton phenotype; embryo phenotype; 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); 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: receptor-mediated endocytosis;multicellular organism development;excretion;cobalamin metabolic process;cobalamin transport;high-density lipoprotein particle clearance;Golgi to plasma membrane protein transport
• Cellular component: extracellular space;plasma membrane;clathrin-coated pit;endosome membrane;integral component of membrane;apical plasma membrane;endocytic vesicle;brush border membrane;protein-containing complex;extracellular exosome
• Molecular function: signaling receptor binding