MICA MHC class I polypeptide-related sequence A [Homo sapiens (human)] - Gene

Summary

Official Symbol: MICAprovided by HGNC
Official Full Name: MHC class I polypeptide-related sequence Aprovided by HGNC
Primary source: HGNC:HGNC:7090
See related: Ensembl:ENSG00000204520 IMGT/GENE-DB:MICA; MIM:600169; AllianceGenome:HGNC:7090
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: MIC-A; PERB11.1
Summary: This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in lung (RPKM 8.7), endometrium (RPKM 7.4) and 25 other tissues See more
Orthologs: all
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Genomic context

Location:: 6p21.33

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (31400711..31415315)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (31256597..31271201)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (31368488..31383092)

Chromosome 6 - NC_000006.12 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
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?

Functional MICA Variants Are Differentially Associated with Immune-Mediated Inflammatory Diseases.
Title: Functional MICA Variants Are Differentially Associated with Immune-Mediated Inflammatory Diseases.
High population frequencies of MICA copy number variations originate from independent recombination events.
Title: High population frequencies of MICA copy number variations originate from independent recombination events.
MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.
Title: MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.
Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).
Title: Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).
Association of MICA gene Exon-5 polymorphism in oral submucous fibrosis.
Title: Association of MICA gene Exon-5 polymorphism in oral submucous fibrosis.
Diseases association with the polymorphic major histocompatibility complex class I related chain a: MICA gene.
Title: Diseases association with the polymorphic major histocompatibility complex class I related chain a: MICA gene.
Analysis of the association between MICA gene polymorphisms and schizophrenia.
Title: Analysis of the association between MICA gene polymorphisms and schizophrenia.
A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.
Title: A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.
GAS6/TAM signaling pathway controls MICA expression in multiple myeloma cells.
Title: GAS6/TAM signaling pathway controls MICA expression in multiple myeloma cells.
Major Histocompatibility Complex Class I Chain-Related alpha (MICA) STR Polymorphisms in COVID-19 Patients.
Title: Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.

Submit: New GeneRIF Correction See all GeneRIFs (378)

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

EBI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides. EBI GWAS Catalog EBI GWAS CatalogPubMed
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of susceptibility loci for cervical cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of a susceptibility locus in STAT4 for Beh&#x000e7;et's disease in Han Chinese in a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. EBI GWAS Catalog EBI GWAS CatalogPubMed
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 (SF2) Nef moderately downregulates MICA A3.01 T cells and HeLa TZM-bl cells	PubMed
	nef	HIV-1 Nef downregulates cell surface expression of MICA, ULBP1 and ULBP2 in natural killer (NK) cells	PubMed
Vpu	vpu	HIV-1 (NL4-3) Vpu moderately downregulates MICA as shown in A3.01 T cells and HeLa TZM-bl cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH46788 (e-PCR)
- UniSTS:2840

C1_2_C (e-PCR)
- UniSTS:239132

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-170012 (e-PCR)
- UniSTS:184434

SHGC-172535 (e-PCR)
- UniSTS:184444

RH46617 (e-PCR)
- UniSTS:25471

D6S1935 (e-PCR)
- UniSTS:67983

G64283 (e-PCR)
- UniSTS:158664

RH70942 (e-PCR)
- UniSTS:49110

C1_2_BB (e-PCR)
- UniSTS:239064

C1_2_D (e-PCR)
- UniSTS:239065

STRMICA (e-PCR)
- UniSTS:239066

RH17599 (e-PCR)
- UniSTS:14045

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables beta-2-microglobulin binding	IDA Inferred from Direct Assay more info	PubMed
enables natural killer cell lectin-like receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables natural killer cell lectin-like receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptide antigen binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	IBA Inferred from Biological aspect of Ancestor more info
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class Ib	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in gamma-delta T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response to tumor cell	IDA Inferred from Direct Assay more info	PubMed
involved_in killing of cells of another organism	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of natural killer cell mediated cytotoxicity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell mediated cytotoxicity	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: MHC class I polypeptide-related sequence A

Names: HLA class I antigen; MHC class I chain-related protein A; MHC class I related chain A; MHC class I related sequence A; major histocompatibility complex class I chain-related protein A; stress inducible class I homolog

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_034139.2 RefSeqGene

Range

7886..19606

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000247.3 → NP_000238.1 MHC class I polypeptide-related sequence A isoform 1 (MICA*001) precursor

See identical proteins and their annotated locations for NP_000238.1

Status: REVIEWED

Description

Transcript Variant: This variant (1*001, also known as 1) is derived from the MICA*001 allele. It encodes the longest isoform (1). The MICA*001 allele is found in the c6_QBL (ALT_REF_LOCI_6) alternate assembly.

Source sequence(s)

BM991681, L14848

UniProtKB/Swiss-Prot

A8KQR0, A9LRW5, A9QVE0, B1VJF1, O60917, O60918, O60919, O60920, O60933, O77956, O78150, O78151, O78152, O78153, O97987, O97988, O97989, O97990, O97991, O97992, O97993, O97994, O97995, O98234, O98235, O98236, O98237, O98238, P79506, P79507, P79508, P79509, P79510, P79511, P79512, P79513, P79514, P79515, P79516, P79517, P79518, P79519, P79520, P79521, Q29983, Q5C9P8, Q5XM81, Q70I48, Q70I49, Q7JFH9, Q7JFI0, Q7JFI1, Q7JFI2, Q7YQ98, Q861I1, Q95464, Q95HA2, Q95HD6, Q95HN4, Q95HN5, Q95HN6, Q95IB2, Q95IY7, Q99692, Q9BCR3, Q9BCR4, Q9BCR5, Q9BCR6, Q9BCR7, Q9BCR8, Q9BCR9, Q9BCS0, Q9BCS1, Q9BCS2, Q9BCS3, Q9BCS4, Q9BD20, Q9GIZ1, Q9GIZ2, Q9GIZ3, Q9GIZ4, Q9GIZ5, Q9GIZ6, Q9GJ01, Q9GJ02, Q9GJ03, Q9GJ04, Q9GJ05, Q9GJ06, Q9GJ07, Q9GJ08, Q9GJ09, Q9MY21, Q9TQ86, Q9TQ87, Q9TQ88, Q9TQ89, Q9TQ92, Q9TQ93, Q9TQ94, Q9TQ95, Q9TQ96, Q9TQ97, Q9TQ98, Q9TQ99, Q9TQA0, Q9TQA1, Q9TQA2, Q9TQA3, Q9TQA4, Q9TQI9, Q9TQJ0, Q9TQJ1, Q9TQJ9, Q9TQK0, Q9TQK1, Q9TQK2, Q9TQK8, Q9TQK9, Q9TQL0, Q9TQL1, Q9TQL2, Q9TQL3, Q9TQL4, Q9UE04, Q9UE05, Q9UE06, Q9UE11

UniProtKB/TrEMBL

A0A5P3YYA7, C5NT78

Conserved Domains (2) summary

cd07698
Location:205 → 296

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

cl08246
Location:24 → 198

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_001177519.3 → NP_001170990.1 MHC class I polypeptide-related sequence A isoform 2 (MICA*00801) precursor

See identical proteins and their annotated locations for NP_001170990.1

Status: REVIEWED

Description

Transcript Variant: This variant (1*00801, also known as 1) is derived from the MICA*00801 allele. It contains a 4 nt insertion (rs9279200) that results in a frameshift and truncation of the CDS, compared to variant 1 (allele MICA*001). The resulting isoform (2) has a shorter and distinct C-terminus, compared to isoform 1. The MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence.

Source sequence(s)

AK299135, BM991681, BX342160, CN483948

Consensus CDS

CCDS56412.1

UniProtKB/TrEMBL

I3WCM9, Q96QC4

Related

ENSP00000413079.1, ENST00000449934.7

Conserved Domains (2) summary

cd21017
Location:203 → 297

IgC1_MHC_Ia_MIC-A_MIC-B; Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; member of the C1-set of Ig superfamily (IgSF) domains

cl08246
Location:24 → 198

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_001289152.2 → NP_001276081.1 MHC class I polypeptide-related sequence A isoform 3 (MICA*00801)

See identical proteins and their annotated locations for NP_001276081.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' exon and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream in-frame start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (3) is shorter at the N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 3; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence. Both variants 2 and 3 encode the same isoform.

Source sequence(s)

AK299135, AL645933, BM552351, BM991681

Consensus CDS

CCDS75421.1

UniProtKB/TrEMBL

A0A024RCL3, A0A024RCS6

Related

ENSP00000482382.1, ENST00000616296.4

Conserved Domains (2) summary

cd07698
Location:108 → 199

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

cl08246
Location:3 → 101

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_001289153.2 → NP_001276082.1 MHC class I polypeptide-related sequence A isoform 3 (MICA*00801)

See identical proteins and their annotated locations for NP_001276082.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' exon and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream in-frame start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (3) is shorter at the N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 2; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence. Both variants 2 and 3 encode the same isoform.

Source sequence(s)

AK299135, BM991681, DT219772

Consensus CDS

CCDS75421.1

UniProtKB/TrEMBL

A0A024RCL3, A0A024RCS6

Conserved Domains (2) summary

cd07698
Location:108 → 199

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

cl08246
Location:3 → 101

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
NM_001289154.2 → NP_001276083.1 MHC class I polypeptide-related sequence A isoform 4 (MICA*00801)

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5' exon and uses an alternate splice site in an internal exon, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from an alternate start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (4) has a distinct and shorter N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 4; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence.

Source sequence(s)

AK094237, AK299135, BM991681, DT219772

Consensus CDS

CCDS93880.1

UniProtKB/TrEMBL

A0A0G2JJ55

Related

ENSP00000501157.1, ENST00000674069.1

Conserved Domains (1) summary

cd07698
Location:67 → 158

IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain