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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 7.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_030943.4	NP_112205.2	12	yes	-
ENST00000299155.10	ENSP00000299155.6	12	yes	-
NM_001425246.1	NP_001412175.1	10	-	-
ENST00000559525.1	ENSP00000453786.1	3	-	-

Phenotypes

GenCC

Source: genCC

• Imerslund-Grasbeck syndrome type 1 (Strong), mode of inheritance: AR
• Imerslund-Grasbeck syndrome (Supportive), 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 (560 variants)
• Imerslund-Grasbeck_syndrome_type_2 (146 variants)
• Inborn_genetic_diseases (83 variants)
• not_provided (31 variants)
• AMN-related_disorder (7 variants)
• Imerslund-Grasbeck_syndrome_type_1 (3 variants)
• Megaloblastic_anemia (2 variants)
• not_specified (2 variants)
• Cobalamin_deficiency (2 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. These statistics are base on transcript: NM_030943.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		6	216	1	224
missense	1	3	154	11		169
nonsense	10	3				13
start loss						0
frameshift	20	17	4			41
splice donor/acceptor (+/-2bp)	2	18	1			21
Total	34	41	165	227	1

Highest pathogenic variant AF is 0.000074668525

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
		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)

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

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