A2ML1 alpha-2-macroglobulin like 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: A2ML1provided by HGNC
Official Full Name: alpha-2-macroglobulin like 1provided by HGNC
Primary source: HGNC:HGNC:23336
See related: Ensembl:ENSG00000166535 MIM:610627; AllianceGenome:HGNC:23336
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: OMS; p170; CPAMD9
Summary: This gene encodes a member of the alpha-macroglobulin superfamily. The encoded protein is thought to be an N-glycosylated monomeric protein that acts as an inhibitor of several proteases. It has been shown to form covalent interactions with proteases, and has been reported as the p170 antigen recognized by autoantibodies in the autoimmune disease paraneoplastic pemphigus (PNP; PMID:20805888). Mutations in these gene have also been associated with some cases of Noonan syndrome (NS; PMID:24939586) as well as some cases of otitis media (PMID:26121085). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
Expression: Restricted expression toward esophagus (RPKM 190.0) See more
Orthologs: all
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Genomic context

Location:: 12p13.31

Exon count:: 40

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (8822621..8887459)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (8805910..8869474)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (8975217..9029383)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A2ML1 Inhibits Esophageal Squamous Cell Carcinoma Progression and Serves as a Novel Prognostic Biomarker.
Title: A2ML1 Inhibits Esophageal Squamous Cell Carcinoma Progression and Serves as a Novel Prognostic Biomarker.
Audiologic Measures in an Indigenous Community with A2ML1- and FUT2-Related Otitis Media.
Title: Audiologic Measures in an Indigenous Community with A2ML1- and FUT2-Related Otitis Media.
Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family.
Title: Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family.
The clinical significance of A2ML1 variants in Noonan syndrome has to be reconsidered.
Title: The clinical significance of A2ML1 variants in Noonan syndrome has to be reconsidered.
Study identified 16 novel A2ML1 variants in otitis media patients, two of which are pathogenic further providing evidence to support a role for A2ML1 in middle ear mucosal pathology. Sequencing of patients salivary RNA samples demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants.
Title: A2ML1 and otitis media: novel variants, differential expression, and relevant pathways.
The functional assessment supported the pathogenicity of the RAF1 and RIT1 variants of unknown significance (VUSs), while the significance of two VUSs in A2ML1 remained unclear.
Title: Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies.
Brain gene expression of PADI2, ZNF385A, PSD2, and A2ML1 and DNA methylation dysregulations are implicated in the alteration of brain tissue properties associated with late-life cognitive decline above and beyond the influence of common neuropathologic conditions.
Title: Association Between Brain Gene Expression, DNA Methylation, and Alteration of Ex Vivo Magnetic Resonance Imaging Transverse Relaxation in Late-Life Cognitive Decline.
The indigenous Filipino population has a ~50% prevalence of otitis media. A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome, and social clusters might modulate the effect of the A2ML1 genotype.
Title: Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population.
A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome.
Title: Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene.
Studies support a role for alpha-2-macroglobulin-like 1 protein (A2ML1) in the pathophysiology of otitis media.
Title: Rare A2ML1 variants confer susceptibility to otitis media.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Otitis media, susceptibility to MedGen: C1833692 OMIM: 166760 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Clone Names

FLJ16045, FLJ25179, FLJ39129, FLJ41597, FLJ41598, FLJ41607, DKFZp686C1729, DKFZp686D2011, DKFZp686G1812, DKFZp686L1821, DKFZp686O1010

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables peptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
involved_in regulation of endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: alpha-2-macroglobulin-like protein 1

Names: C3 and PZP-like, alpha-2-macroglobulin domain containing 9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_042857.2 RefSeqGene

Range

5002..59168

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001282424.3 → NP_001269353.2 alpha-2-macroglobulin-like protein 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents use of an alternate promoter, and thus differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate AUG, and the resulting isoform (2) has a distinct and shorter N-terminus compared to isoform 1.

Source sequence(s)

AC006513, AC006581

Consensus CDS

CCDS73439.1

UniProtKB/TrEMBL

H0YGG5

Related

ENSP00000438292.1, ENST00000539547.5

Conserved Domains (4) summary

cd02897
Location:465 → 760

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:245 → 335

A2M; Alpha-2-macroglobulin family

pfam07677
Location:871 → 958

A2M_recep; A-macroglobulin receptor

pfam07703
Location:1 → 110

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
NM_144670.6 → NP_653271.3 alpha-2-macroglobulin-like protein 1 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC006513, AC006581

Consensus CDS

CCDS8596.2

UniProtKB/Swiss-Prot

A8K2U0, B5MDD1, B7Z7V4, D3DUV3, F5H2Z2, Q2M224, Q6ZW52, Q6ZW53, Q8N1M4, Q96LQ8

UniProtKB/TrEMBL

B3KVV6

Related

ENSP00000299698.7, ENST00000299698.12

Conserved Domains (5) summary

cd02897
Location:956 → 1251

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:736 → 826

A2M; Alpha-2-macroglobulin family

pfam01835
Location:122 → 211

A2M_N; MG2 domain

pfam07677
Location:1362 → 1449

A2M_recep; A-macroglobulin receptor

pfam07703
Location:459 → 601

A2M_N_2; Alpha-2-macroglobulin family N-terminal region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

8822621..8887459

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011520566.3 → XP_011518868.1 alpha-2-macroglobulin-like protein 1 isoform X1

See identical proteins and their annotated locations for XP_011518868.1

UniProtKB/TrEMBL

B3KVV6

Conserved Domains (7) summary

COG2373
Location:123 → 1055

YfaS; Uncharacterized conserved protein YfaS, alpha-2-macroglobulin family [General function prediction only]

cd02897
Location:969 → 1264

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:749 → 839

A2M; Alpha-2-macroglobulin family

pfam01835
Location:122 → 211

A2M_N; MG2 domain

pfam07677
Location:1375 → 1462

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1021 → 1266

A2M_comp; A-macroglobulin complement component

pfam07703
Location:455 → 613

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
XM_047428387.1 → XP_047284343.1 alpha-2-macroglobulin-like protein 1 isoform X4
XM_011520567.3 → XP_011518869.1 alpha-2-macroglobulin-like protein 1 isoform X1

See identical proteins and their annotated locations for XP_011518869.1

UniProtKB/TrEMBL

B3KVV6

Conserved Domains (7) summary

COG2373
Location:123 → 1055

YfaS; Uncharacterized conserved protein YfaS, alpha-2-macroglobulin family [General function prediction only]

cd02897
Location:969 → 1264

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:749 → 839

A2M; Alpha-2-macroglobulin family

pfam01835
Location:122 → 211

A2M_N; MG2 domain

pfam07677
Location:1375 → 1462

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1021 → 1266

A2M_comp; A-macroglobulin complement component

pfam07703
Location:455 → 613

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
XM_017018869.2 → XP_016874358.1 alpha-2-macroglobulin-like protein 1 isoform X2

UniProtKB/TrEMBL

B3KVV6
XM_017018870.2 → XP_016874359.1 alpha-2-macroglobulin-like protein 1 isoform X3

UniProtKB/Swiss-Prot

A8K2U0, B5MDD1, B7Z7V4, D3DUV3, F5H2Z2, Q2M224, Q6ZW52, Q6ZW53, Q8N1M4, Q96LQ8

UniProtKB/TrEMBL

B3KVV6

Conserved Domains (5) summary

cd02897
Location:956 → 1251

A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...

pfam00207
Location:736 → 826

A2M; Alpha-2-macroglobulin family

pfam01835
Location:122 → 211

A2M_N; MG2 domain

pfam07677
Location:1362 → 1449

A2M_recep; A-macroglobulin receptor

pfam07703
Location:459 → 601

A2M_N_2; Alpha-2-macroglobulin family N-terminal region