AMN

protein-coding

amnion associated transmembrane protein

Gene summary

The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

MANE transcript

NM_030943.4

Inheritance

ClinVar variants

P:73U:164B:229

Top phenotype

Imerslund-Grasbeck syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr14:102,922,663-102,933,596

External References & Databases

Ensembl (ENSG00000166126)

Transcript & Mutation Effects

hg38 • Region Span ~10.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Imerslund-Grasbeck syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009853

Submitter: Orphanet

Imerslund-Grasbeck syndrome type 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100157

Submitter: PanelApp Australia

Imerslund-Grasbeck syndrome type 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100157

Submitter: Natera

Imerslund-Grasbeck syndrome type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100156

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Imerslund-Grasbeck syndrome 2AR

Manifestation: Gastrointestinal; Hematologic; Renal

Intervention: Gastrointestinal

Rationale: Early diagnosis is beneficial, as early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality

Refs: 12590260; 17114957; 17285242; 18181028; 22078000; 22854512; 22631584

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMN variants in ClinVar

9 Conditions Cataloged

Imerslund-Grasbeck syndromeTotal: 560

Imerslund-Grasbeck syndrome type 2Total: 152

Inborn genetic diseasesTotal: 86

not providedTotal: 34

not specifiedTotal: 34

AMN-related disorderTotal: 13

Imerslund-Grasbeck syndrome type 1Total: 3

Megaloblastic anemiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030943.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	217 clinvar		222
missense	1 clinvar	3 clinvar	155 clinvar	12 clinvar		171
nonsense	9 clinvar	4 clinvar				13
start loss						0
frameshift	18 clinvar	18 clinvar	4 clinvar			40
splice donor/acceptor (+/-2bp)	2 clinvar	18 clinvar				20
Total	30	43	164	229	0	466

Highest pathogenic variant AF is 0.000074668525

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030943.4	RefSeq	NP_112205.2	12	MANE Select
ENST00000299155.10	Ensembl	ENSP00000299155.6	12	MANE Select
NM_001425246.1	RefSeq	NP_001412175.1	10	Standard
ENST00000559525.1	Ensembl	ENSP00000453786.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HDL clearance
Cobalamin (Cbl, vitamin B12) transport and metabolism
Metabolism
Plasma lipoprotein clearance
Transport of small molecules

Biological Process

receptor-mediated endocytosis
multicellular organism development
excretion
cobalamin metabolic process
cobalamin transport

Molecular Function

signaling receptor binding

Cellular Component

extracellular space
plasma membrane
clathrin-coated pit
endosome membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299155
Coding exons: 12
Length: 10941
Individuals with no LoFs: 125471
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125508
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.606	230	257	0.894	0.0000126	2784
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00020	0.00018	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.208

Gene Damage Prediction

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