MICB

Summary

MICB (MHC class I polypeptide-related sequence B, HGNC:7091) is a protein-coding gene on chromosome 6p21.33, encoding MHC class I polypeptide-related sequence B (Q29980). Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.

This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4277 — RefSeq curated summary.

At a glance

• GWAS associations: 109
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_005931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7091
Approved symbol	MICB
Name	MHC class I polypeptide-related sequence B
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	PERB11.2
Ensembl gene	ENSG00000204516
Ensembl biotype	protein_coding
OMIM	602436
Entrez	4277

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000252229, ENST00000399150, ENST00000494577, ENST00000538442

RefSeq mRNA: 3 — MANE Select: NM_005931 NM_001289160, NM_001289161, NM_005931

CCDS: CCDS43449, CCDS75422, CCDS75423

Canonical transcript exons

ENST00000252229 — 6 exons

Exon	Start	End
ENSE00001691563	31506143	31506430
ENSE00001842955	31498145	31498263
ENSE00001874794	31509782	31511124
ENSE00003504401	31507022	31507300
ENSE00003559511	31505617	31505871
ENSE00003582988	31507400	31507531

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 87.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6774 / max 154.1745, expressed in 1279 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66887	3.3099	665
66885	1.6267	741
66886	0.7407	430

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	87.77	gold quality
leukocyte	CL:0000738	86.67	gold quality
monocyte	CL:0000576	86.51	gold quality
blood	UBERON:0000178	85.71	gold quality
stromal cell of endometrium	CL:0002255	85.01	gold quality
lymph node	UBERON:0000029	84.67	gold quality
bone marrow	UBERON:0002371	83.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.21	gold quality
bone marrow cell	CL:0002092	81.81	gold quality
spleen	UBERON:0002106	81.31	gold quality
vermiform appendix	UBERON:0001154	80.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.67	gold quality
apex of heart	UBERON:0002098	77.09	gold quality
upper lobe of left lung	UBERON:0008952	76.87	gold quality
right lung	UBERON:0002167	75.32	gold quality
lung	UBERON:0002048	74.39	gold quality
duodenum	UBERON:0002114	74.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.22	gold quality
smooth muscle tissue	UBERON:0001135	74.08	gold quality
small intestine	UBERON:0002108	73.57	gold quality
right coronary artery	UBERON:0001625	73.37	gold quality
ascending aorta	UBERON:0001496	73.06	gold quality
thoracic aorta	UBERON:0001515	73.04	gold quality
descending thoracic aorta	UBERON:0002345	72.83	gold quality
left coronary artery	UBERON:0001626	72.30	gold quality
mucosa of transverse colon	UBERON:0004991	72.15	gold quality
myometrium	UBERON:0001296	71.91	gold quality
omental fat pad	UBERON:0010414	71.74	gold quality
adipose tissue	UBERON:0001013	71.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, GATA2, HDAC1, HSF1, SP1, SP3, STAT3

miRNA regulators (miRDB)

54 targeting MICB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4498	99.47	67.42	2360

Literature-anchored findings (GeneRIF, showing 40)

• an Alu repeat dimorphism within the first intron of the MICB gene was found (PMID:11862397)
• From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid (PMID:11881819)
• high frequency of the MIC null haplotype, HLA-B48-MICA-del-MICB*0107 N, in the Angaite Amerindian community in Paraguay (PMID:12242594)
• binding of MICA and MICB induces endocytosis and downregulation of NKG2D, and in turn severe impairment of the responsiveness of tumour-antigen-specific effector T cells (PMID:12384702)
• Alternatively spliced forms of MICA and MICB lacking exon 3 in a human cell line and evidence of presence of similar RNA in human peripheral blood mononuclear cells (PMID:12466900)
• MICB is induced on dendritic cells upon IFN-alpha stimulation and is capable of activating NK cells by a mechanism that is impaired in hepatitis C virus infection. (PMID:12538683)
• micb, overexpressed on a subset of human HCCs, may play an important role in their susceptibility to NK cells. (PMID:12569559)
• Determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies. (PMID:12714493)
• Circulating soluble MICB in cancer patients deactivates natural killer (NK) cell-mediated NK immunity by down-modulating important activating and chemokine receptors in vitro and in vivo. (PMID:14662896)
• new allele is identical to MICB-0103101v except for a single mutation of G to A in exon 4 that translates into an amino acid substitution from glutamic acid to lysine (PMID:15191526)
• eight novel MICB variants, including a null allele, which were identified in peripheral blood leukocytes of gastric MALT lymphoma patients. (PMID:15304008)
• The polymorphisms and haplotype distributions of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population have their own distinct genetic characteristics (PMID:15304009)
• analysis of human, chimpanzee and rhesus monkey MHC-B and MHC-C DNA gives insight to the time frame of human divergence from Old World monkeys (PMID:15967992)
• Engagement of MIC by NKG2D promotes spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against HTLV-1-infected T cells. (PMID:16568261)
• MICB-CA18 is positively associated with ulcerative colitis and female ulcerative colitis patients in a Chinese population. (PMID:16679067)
• MICB, the second member of the human MIC protein family, is likewise shed by metalloproteases from tumor cells and is present in sera of patients with gastrointestinal tumors. (PMID:16698441)
• MICB promoter polymorphism haplotypes showed strong linkage disequilibrium with MICB alleles. (PMID:16698444)
• NKG2D and MICB in the cytotoxic NK cell immune synapse have roles in NK cell cytotoxic function (PMID:16849432)
• In a study of mainly paucibacillary leprosy-affected sib-pair families from South India, we have identified significant association with a functional variant of the MICA gene as well as a microsatellite in the flanking region of the MICB gene. (PMID:16923796)
• reveal distinct modes of activation of the genes for the MIC ligands of NKG2D and provide a molecular framework for analyses of gene regulation under different cellular insult conditions (PMID:17202358)
• variations in MICB expression among normal individuals could imply a significant difference in the natural immune response against infections or tumor transformation (PMID:17557375)
• MICB protein polymorphism is implicated in human herpes virus seropositivity and schizophrenia risk. (PMID:17561376)
• study shows MICA & MICB, with exception of the central nervous system, is widely transcribed; data question previous assumptions, correlating a tissue-specific expression/induction of MIC in relevance to auto-immune or tumor processes (PMID:17565371)
• Data show that expression of NKG2D ligands MICA and MICB on CNE2 and CNE2/DDP cells is correlated with NK cell-mediated lysis. (PMID:17584663)
• upregulation of MICA and MICB by treatment with TsA leads to enhancement of the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells (PMID:17625602)
• study shows that human cytomegalovirus-miR-UL112 specifically down-regulates MICB expression during viral infection, leading to decreased binding of NKG2D and reduced killing by NK cells (PMID:17641203)
• study reports that the MICB 0050204(1) allele, present in the majority of the Spanish population (70% of healthy controls) is characterized by the presence of an extra exon found between the sequence corresponding to exon 1 and 2 (PMID:17678727)
• while infection with wild-type Ad enhances synthesis of the NKG2D ligands, MICA and MICB, their expression on the cell surface is actively suppressed. (PMID:18287244)
• Common MICA and MICB genetic variations are not associated with susceptibility to type 1 diabetes. (PMID:18332098)
• As NKG2D ligand, MICB are expressed on immature dendritic cells and plays an important role in the cytotoxic effect of NK cells against iDC. (PMID:18394338)
• Elevated soluble MICB levels exist in serum of multiple sclerosis patients related with disease activity. (PMID:18486757)
• MICB*004 allele frequency is significantly increased in multiple sclerosis patients. (PMID:18588574)
• Expression of MICA/B was detected in 97.6 of ovarian cancer cells,but not on normal ovarian epithelium. The expression of MICA/B in ovarian cancer was highly correlated with that of ULBP2. (PMID:18791713)
• shedding of the immunostimulatory MHC class I chain-related gene B prevents tumor formation (PMID:19147769)
• CD14(+) monocytes promote NKG2D(+)CD4(+) T cells activation through the NKG2D-MIC engagement in the pathogenesis of systemic lupus erytematosus. (PMID:19200602)
• Growth supernatant from propionibacteria or propionate alone could directly stimulate functional MICA/B surface expression and MICA promoter activity by a mechanism dependent on intracellular calcium (PMID:19553547)
• MICB0106 allele was positively associated with ulcerative colitis in the Han Chinese population in central China. (PMID:19662431)
• An association is reported between MICA and MICB in Alzheimer disease. (PMID:19691640)
• mutation of T14 and M82 in the adenovirus early transcription unit 3 selectively compromised MICA/B downregulation (PMID:19949079)
• These results provide initial clues to the importance of examining the impact of genetic variations(MICB) or environmental factors in the background of the other. (PMID:20138739)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mill2	ENSMUSG00000040987
mus_musculus	Mill1	ENSMUSG00000054005
rattus_norvegicus	Mill1	ENSRNOG00000017699
rattus_norvegicus	Micb	ENSRNOG00000057645

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

MHC class I polypeptide-related sequence B — Q29980 (reviewed: Q29980)

All UniProt accessions (3): Q29980, A0A7D9H7X8, F5H7Q8

UniProt curated annotations — full annotation on UniProt →

Function. Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells. Up-regulated in stressed conditions, such as viral and bacterial infections or DNA damage response, serves as signal of cellular stress, and engagement of KLRK1/NKG2D by MICA triggers NK-cells resulting in a range of immune effector functions, such as cytotoxicity and cytokine production.

Subunit / interactions. Unlike classical MHC class I molecules, does not form a heterodimer with beta-2-microglobulin. Binds as a monomer to a KLRK1/NKG2D homodimer. KLRK1 forms a complex with HCST/DAP10 in which KLRK1 binds MICB while HCST acts as an adapter molecule which enables signal transduction. Receptor-ligand interaction induces clustering of both proteins in ordered structures called immune synapses and also leads to their intercellular transfer. This is associated with a reduction in the cytotoxicity of KLRK1-expressing cells. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 glycoprotein UL16; this interaction causes sequestration of MICB in the endoplasmic reticulum and increases resistance to KLRK1-mediated cytotoxicity.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed with the exception of the central nervous system where it is absent. Expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In hepatocellular carcinomas, expressed in tumor cells but not in surrounding non-cancerous tissue.

Post-translational modifications. Proteolytically cleaved and released from the cell surface of tumor cells.

Disease relevance. Rheumatoid arthritis (RA) [MIM:180300] An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Disease susceptibility is associated with variants affecting the gene represented in this entry. The MICB*004 allele is associated with rheumatoid arthritis. Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.

Induction. By heat shock, oxidative stress, retinoic acid, IFN-alpha and the DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine. Induction by IFN-alpha is impaired in patients with chronic hepatitis C virus infection. Down-regulated by human cytomegalovirus UL112 microRNA during viral infection which leads to decreased binding of KLRK1/NKG2D and reduced killing by natural killer cells.

Polymorphism. The following alleles of MICB are known: MICB001, MICB002, MICB003, MICB004, MICB005, MICB006, MICB007, MICB008, MICB009N, MICB010, MICB011, MICB012, MICB013, MICB014, MICB015, MICB016, MICB018, MICB019, MICB020, MICB021N and MICB022. MICB009N and MICB021N are null alleles which are not expressed. The three most common MICB alleles in the human population could be MICB005, MICB004, and MICB002. The sequence shown is that of MICB*004.

Miscellaneous. A GC to AG nucleotide substitution in intron 1 generates a splice junction which gives rise to an additional exon between exons 1 and 2. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the MHC class I family. MIC subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q29980-1	1, MICB1	yes
Q29980-2	2, MICB2, ex3-del
Q29980-3	3

RefSeq proteins (3): NP_001276089, NP_001276090, NP_005922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129, PF07654

UniProt features (54 total): strand 16, sequence variant 15, helix 6, glycosylation site 4, splice variant 3, disulfide bond 2, topological domain 2, turn 2, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2WY3	X-RAY DIFFRACTION	1.8
1JE6	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q29980-F1	79.09	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 119–187, 225–282

Glycosylation sites (4): 164, 210, 220, 261

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 200 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BENPORATH_ES_WITH_H3K27ME3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOZGIT_ESR1_TARGETS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_317, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GCM_RING1, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_RESPONSE_TO_STRESS

GO Biological Process (12): adaptive immune response (GO:0002250), immune response-activating cell surface receptor signaling pathway (GO:0002429), immune response (GO:0006955), response to oxidative stress (GO:0006979), response to heat (GO:0009408), killing of cells of another organism (GO:0031640), response to retinoic acid (GO:0032526), gamma-delta T cell activation (GO:0046629), negative regulation of defense response to virus by host (GO:0050689), immune system process (GO:0002376), negative regulation of defense response (GO:0031348), regulation of immune response (GO:0050776)

GO Molecular Function (1): natural killer cell lectin-like receptor binding (GO:0046703)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
response to stress	2
cellular anatomical structure	2
immune response-activating signaling pathway	1
immune response-regulating cell surface receptor signaling pathway	1
immune system process	1
response to stimulus	1
response to temperature stimulus	1
cell killing	1
disruption of cell in another organism	1
response to lipid	1
response to oxygen-containing compound	1
T cell activation	1
negative regulation of defense response to virus	1
regulation of defense response to virus by host	1
biological_process	1
defense response	1
regulation of defense response	1
negative regulation of response to stimulus	1
regulation of immune system process	1
regulation of response to stimulus	1
signaling receptor binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

40 interactions, top by confidence:

A	B	Type	Score
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
PVR	ORC4	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
PPT1	MICB	psi-mi:“MI:0915”(physical association)	0.400
MICB	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
PLD6	HSPA5	psi-mi:“MI:0914”(association)	0.350
ITGB8	TARS3	psi-mi:“MI:0914”(association)	0.350
TUBB2B	POTEF	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
NUBP2	TK2	psi-mi:“MI:0914”(association)	0.350
MICA	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
VSIG4	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
TUBB2A	RAD51C	psi-mi:“MI:0914”(association)	0.350
GDF3	IDH3B	psi-mi:“MI:0914”(association)	0.350
TRUB2	PTCD1	psi-mi:“MI:0914”(association)	0.350
SLC25A22	IPO13	psi-mi:“MI:0914”(association)	0.350
TUBB6	TCP1	psi-mi:“MI:0914”(association)	0.350
GINM1	KDELR1	psi-mi:“MI:0914”(association)	0.350
DHRS9	SLAMF1	psi-mi:“MI:0914”(association)	0.350
HDHD3	PCCA	psi-mi:“MI:0914”(association)	0.350
ARHGEF10	ICAM1	psi-mi:“MI:0914”(association)	0.350
RYK	DUSP14	psi-mi:“MI:0914”(association)	0.350
LTO1	USP11	psi-mi:“MI:0914”(association)	0.350
MICB	LGALS8	psi-mi:“MI:0914”(association)	0.350
SPSB3	PEX14	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): MICB (Affinity Capture-MS), MICB (Affinity Capture-RNA), BMP2K (Affinity Capture-MS), CLTA (Affinity Capture-MS), FAU (Affinity Capture-MS), MYL9 (Affinity Capture-MS), MYO1E (Affinity Capture-MS), RPL36A (Affinity Capture-MS), RPL37A (Affinity Capture-MS), SERBP1 (Affinity Capture-MS), GPD1L (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), SLC25A30 (Affinity Capture-MS), GJA1 (Affinity Capture-MS), ARL17A (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K7V7, C1ITJ8, O08602, O08603, O08604, O19477, O35799, P01901, P01902, P06339, P13599, P14427, P14432, P16391, P25311, P26151, P30383, P55899, P60018, P70387, Q01965, Q29980, Q29983, Q2KN22, Q30201, Q3B8P2, Q5RD09, Q60I18, Q61559, Q63678, Q64726, Q6H3X3, Q8HWB0, Q8HWE5, Q8HWE7, Q8SPV9, Q8VD31, Q920A9, Q95460, Q9BCU3

Diamond homologs: A0A0G2K7V7, O19477, O35799, P01896, P01899, P01900, P01901, P10321, P13752, P15979, P16391, P30377, P30379, P30380, P30381, P30386, P30388, P30511, P30516, P60018, P70387, Q29980, Q29983, Q30201, Q60I18, Q8HWE5, Q8HWE7, Q9GKZ0, Q9GL41, Q9GL42, Q9GL43, C1ITJ8, P01885, P01888, P01889, P01893, P01894, P01895, P01897, P01898

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-dependent Golgi-to-ER retrograde traffic	5	12.1×	2e-03
SLC-mediated transmembrane transport	6	7.7×	2e-03
Transport of small molecules	8	4.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

734 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31507020:A:AG	acceptor_gain	1.0000
6:31507021:G:GG	acceptor_gain	1.0000
6:31507021:GT:G	acceptor_gain	1.0000
6:31507297:TCTGG:T	donor_loss	1.0000
6:31507298:CTGG:C	donor_loss	1.0000
6:31507299:TGG:T	donor_loss	1.0000
6:31507300:GGTG:G	donor_loss	1.0000
6:31507301:GT:G	donor_loss	1.0000
6:31507302:T:G	donor_loss	1.0000
6:31498260:GCTG:G	donor_gain	0.9900
6:31498262:TGGTG:T	donor_loss	0.9900
6:31498263:GGTG:G	donor_loss	0.9900
6:31498264:G:GG	donor_gain	0.9900
6:31498264:G:T	donor_loss	0.9900
6:31498265:T:A	donor_loss	0.9900
6:31498266:GA:G	donor_loss	0.9900
6:31505616:GA:G	acceptor_gain	0.9900
6:31505869:G:GT	donor_gain	0.9900
6:31507017:TCCA:T	acceptor_loss	0.9900
6:31507018:CCAGT:C	acceptor_loss	0.9900
6:31507019:CAG:C	acceptor_loss	0.9900
6:31507020:AG:A	acceptor_loss	0.9900
6:31507020:AGT:A	acceptor_gain	0.9900
6:31507021:GTG:G	acceptor_gain	0.9900
6:31507021:GTGC:G	acceptor_gain	0.9900
6:31507021:GTGCC:G	acceptor_gain	0.9900
6:31507281:C:T	donor_gain	0.9900
6:31507301:G:GG	donor_gain	0.9900
6:31507303:GA:G	donor_loss	0.9900
6:31507398:A:AG	acceptor_gain	0.9900

AlphaMissense

2502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31507096:T:C	F230L	0.969
6:31507098:C:A	F230L	0.969
6:31507098:C:G	F230L	0.969
6:31505679:T:C	F45L	0.924
6:31505681:T:A	F45L	0.924
6:31505681:T:G	F45L	0.924
6:31507246:T:C	F280L	0.917
6:31507248:C:A	F280L	0.917
6:31507248:C:G	F280L	0.917
6:31505712:T:C	F56L	0.900
6:31505714:C:A	F56L	0.900
6:31505714:C:G	F56L	0.900
6:31507125:G:C	W239C	0.895
6:31507125:G:T	W239C	0.895
6:31507123:T:A	W239R	0.869
6:31507123:T:C	W239R	0.869
6:31505762:G:C	W72C	0.829
6:31505762:G:T	W72C	0.829
6:31507081:T:A	C225S	0.815
6:31507082:G:C	C225S	0.815
6:31506235:T:C	F140L	0.813
6:31506237:C:A	F140L	0.813
6:31506237:C:G	F140L	0.813
6:31506214:T:C	F133L	0.806
6:31506216:C:A	F133L	0.806
6:31506216:C:G	F133L	0.806
6:31507081:T:C	C225R	0.804
6:31507097:T:C	F230S	0.802
6:31507097:T:G	F230C	0.798
6:31505713:T:C	F56S	0.787

dbSNP variants (sampled 300 via entrez): RS1000282069 (6:31499917 T>C), RS1000436148 (6:31493917 G>A,T), RS1000630874 (6:31498404 TG>T), RS1000997582 (6:31510246 G>A), RS1001040824 (6:31511356 G>A), RS1002009311 (6:31504720 G>A,T), RS1002165855 (6:31497663 T>C), RS1002216449 (6:31510909 T>C), RS1002272587 (6:31504366 T>C), RS1002955646 (6:31509422 G>T), RS1003779585 (6:31496539 T>C), RS1004236459 (6:31496205 T>C), RS1004758288 (6:31494381 TG>T), RS1004849028 (6:31498895 C>A,T), RS1005155965 (6:31506065 G>A,C)

Disease associations

OMIM: gene MIM:602436 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

109 associations (top):

Study	Trait	p-value
GCST000308_1	AIDS progression	3.000000e-19
GCST001251_6	Pulmonary function	2.000000e-07
GCST001278_1	Dengue shock syndrome	4.000000e-11
GCST001387_4	Hodgkin’s lymphoma	7.000000e-16
GCST001436_19	Metabolic syndrome	2.000000e-08
GCST001729_10	Crohn’s disease	5.000000e-28
GCST001768_6	Behcet’s disease	2.000000e-10
GCST002084_12	Allergic sensitization	4.000000e-08
GCST002211_10	Psychosis (atypical)	4.000000e-06
GCST002884_5	Cutaneous lupus erythematosus	3.000000e-14
GCST003092_17	Myositis	5.000000e-49
GCST003092_18	Myositis	3.000000e-43
GCST003092_19	Myositis	1.000000e-49
GCST003092_21	Myositis	4.000000e-48
GCST003184_39	Atopic dermatitis	2.000000e-06
GCST003858_9	Oral cavity cancer	7.000000e-08
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004285_1	Midgestational circulating levels of PBDEs	2.000000e-06
GCST004285_5	Midgestational circulating levels of PBDEs	8.000000e-07
GCST004285_7	Midgestational circulating levels of PBDEs	3.000000e-07
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_19	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_27	Autism spectrum disorder or schizophrenia	1.000000e-09

EFO canonical traits (24, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0000195	metabolic syndrome
EFO:0005298	allergic sensitization measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0007985	platelet crit
EFO:0005091	monocyte count
EFO:0008402	susceptibility to cold sores measurement
EFO:0008403	susceptibility to mononucleosis measurement
EFO:0008410	susceptibility to pneumonia measurement
EFO:0009180	rosacea severity measurement
EFO:0007796	parental longevity
EFO:0009458	alcohol use disorder measurement
EFO:0004517	arterial stiffness measurement
EFO:0009902	handedness
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004309	platelet count
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3828913	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3828913	MICB	3	3.00	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin

CTD chemical–gene interactions

68 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
methylmercuric chloride	increases expression, affects cotreatment	4
sodium arsenite	affects expression, affects methylation, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Arsenic	affects methylation, increases abundance, increases expression	3
Cyclosporine	decreases expression	3
entinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	affects expression, increases reaction, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
butyraldehyde	increases expression	1
triadimefon	decreases expression	1
pentanal	increases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8KH	Abcam HCT 116 MICB KO	Cancer cell line	Male
CVCL_B9MR	Abcam A-549 MICB KO	Cancer cell line	Male
CVCL_D2GE	Abcam MCF-7 MICB KO	Cancer cell line	Female
CVCL_E6UL	Genomeditech HEK-293 H_MICB	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.