MICA

MHC class I polypeptide-related sequence A, the group of C1-set domain containing

Basic information

Region (hg38): 6:31399783-31415315

Links

ENSG00000204520 ∙ NCBI:100507436 ∙ OMIM:600169 ∙ HGNC:7090 ∙ Uniprot:Q29983 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (10 variants)
• not specified (6 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MICA 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						0
missense			10	2	3	15
nonsense						0
start loss						0
frameshift					3	3
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region						0
non coding						0
Total	0	0	10	3	6

Variants in MICA

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

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

Position	Type	Phenotype	Significance	ClinVar
6-31403676-C-T		not specified	Uncertain significance (Nov 17, 2022)
6-31410552-G-A		not specified	Uncertain significance (Apr 26, 2023)
6-31410557-C-T		not specified	Uncertain significance (Jan 07, 2022)
6-31410616-G-C		not specified	Uncertain significance (Jan 23, 2023)
6-31410644-C-T		not specified	Uncertain significance (Sep 20, 2023)
6-31410665-A-G		not specified	Uncertain significance (Dec 09, 2023)
6-31410798-G-A			Likely benign (Sep 01, 2023)
6-31411146-T-C		not specified	Uncertain significance (Feb 08, 2023)
6-31411234-T-C		not specified	Uncertain significance (Nov 17, 2022)
6-31411297-A-G		not specified	Uncertain significance (Oct 13, 2023)
6-31411341-G-A			Likely benign (Jan 01, 2023)
6-31411342-T-C		not specified	Uncertain significance (Sep 17, 2021)
6-31412040-T-C		not specified	Benign (Mar 28, 2016)
6-31412063-G-C		not specified	Benign (Apr 17, 2015)
6-31412094-G-T		not specified	Uncertain significance (Nov 03, 2022)
6-31412130-C-A		not specified	Uncertain significance (Jan 25, 2023)
6-31412154-G-A		not specified	Benign (Mar 28, 2016)
6-31412195-G-A		not specified	Uncertain significance (May 03, 2023)
6-31412336-G-A			Likely benign (Jan 01, 2023)
6-31412380-TGCTG-T		not specified	Benign (Mar 28, 2016)
6-31412384-G-GCT		not specified	Benign (Mar 28, 2016)
6-31412384-G-GCTGCTGCTGCT		not specified	Benign (Mar 28, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MICA	protein_coding	protein_coding	ENST00000449934	5	11737

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00497	0.970	114318	0	7	114325	0.0000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.802	144	174	0.829	0.00000886	2116
Missense in Polyphen		46	55.848	0.82367		773
Synonymous	0.658	59	65.8	0.897	0.00000337	607
Loss of Function	1.96	6	13.9	0.432	6.42e-7	166

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000302	0.000302
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T- cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis. {ECO:0000269|PubMed:10426993, ECO:0000269|PubMed:11224526, ECO:0000269|PubMed:11491531, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:9497295}.
• Disease: DISEASE: Note=Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma.; DISEASE: Psoriasis 1 (PSORS1) [MIM:177900]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). {ECO:0000269|PubMed:10323458}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Allograft Rejection;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System (Consensus)

Intolerance Scores

• rvis_EVS: 3.71
• rvis_percentile_EVS: 99.56

Haploinsufficiency Scores

• pHI: 0.0953
• hipred: N
• hipred_score: 0.148

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.101

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: T cell mediated cytotoxicity;immune response to tumor cell;immune response;cellular response to DNA damage stimulus;response to heat;viral process;cytolysis;natural killer cell activation;negative regulation of natural killer cell activation;natural killer cell mediated cytotoxicity;susceptibility to natural killer cell mediated cytotoxicity;defense response to bacterium;negative regulation of natural killer cell mediated cytotoxicity;gamma-delta T cell activation;regulation of immune response;defense response to virus
• Cellular component: extracellular space;cytoplasm;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface
• Molecular function: protein binding;beta-2-microglobulin binding;natural killer cell lectin-like receptor binding