MPIG6B

megakaryocyte and platelet inhibitory receptor G6b

Basic information

Region (hg38): 6:31718594-31726714

Previous symbols: [ "C6orf25" ]

Links

ENSG00000204420 ∙ NCBI:80739 ∙ OMIM:606520 ∙ HGNC:13937 ∙ Uniprot:O95866 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombocytopenia, anemia, and myelofibrosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia, anemia, and myelofibrosis	AR	Hematologic; Oncologic	Individuals have been described with myelofibrosis and early-childhood onset thrombocytopenia and anemia, and the use of RBC transfusions have been described (as well as iron and B12/folic acid)	Hematologic; Oncologic	27743390

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPIG6B gene.

• not provided (2 variants)
• Thrombocytopenia, anemia, and myelofibrosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPIG6B 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				1	1	2
missense			5	3	2	10
nonsense	1	2				3
start loss						0
frameshift	2	2				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	3	4	5	4	3

Highest pathogenic variant AF is 0.00000657

Variants in MPIG6B

This is a list of pathogenic ClinVar variants found in the MPIG6B region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31719160-G-T		not specified	Uncertain significance (Jan 03, 2024)
6-31719167-G-A		not specified	Uncertain significance (Aug 17, 2022)
6-31719176-C-T		not specified	Uncertain significance (Aug 02, 2023)
6-31719235-T-C		not specified	Likely benign (Feb 15, 2023)
6-31719250-G-C			Benign (May 03, 2018)
6-31719284-G-A		not specified	Uncertain significance (Jan 24, 2024)
6-31719300-C-G		not specified	Uncertain significance (May 11, 2022)
6-31720149-C-T		not specified	Uncertain significance (Jan 31, 2023)
6-31720150-G-A		not specified	Uncertain significance (Jan 23, 2024)
6-31720152-T-G		not specified	Uncertain significance (Jan 20, 2023)
6-31723412-TG-T			Pathogenic (Sep 07, 2022)
6-31723654-GC-G			Pathogenic (Dec 13, 2018)
6-31723709-G-C		Thrombocytopenia;Abnormal bleeding	Uncertain significance (May 01, 2020)
6-31723724-C-CT		Thrombocytopenia, anemia, and myelofibrosis	Likely pathogenic (Mar 26, 2024)
6-31723762-C-A		MPIG6B-related disorder	Likely benign (Feb 21, 2023)
6-31723825-G-A		Thrombocytopenia, anemia, and myelofibrosis	Uncertain significance (Feb 05, 2020)
6-31723869-T-C			Likely benign (Sep 01, 2023)
6-31723889-C-A		MPIG6B-related disorder	Benign (Dec 23, 2019)
6-31723900-G-T		Thrombocytopenia, anemia, and myelofibrosis	Uncertain significance (May 22, 2022)
6-31723901-C-A		Thrombocytopenia, anemia, and myelofibrosis	Pathogenic (Sep 01, 2022)
6-31723908-CG-C		Thrombocytopenia, anemia, and myelofibrosis	Likely pathogenic (Oct 30, 2023)
6-31723914-G-T		Thrombocytopenia, anemia, and myelofibrosis	Likely pathogenic (-)
6-31723919-CGA-C		Thrombocytopenia, anemia, and myelofibrosis	Likely pathogenic (Mar 29, 2024)
6-31724221-G-A		Thrombocytopenia, anemia, and myelofibrosis	Pathogenic (Apr 09, 2024)
6-31724604-C-A		Thrombocytopenia, anemia, and myelofibrosis	Uncertain significance (Mar 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPIG6B	protein_coding	protein_coding	ENST00000375806	6	8121

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000108	0.355	125702	0	44	125746	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	126	163	0.771	0.0000113	1490
Missense in Polyphen		41	56.181	0.72978		555
Synonymous	1.65	57	75.1	0.759	0.00000542	560
Loss of Function	0.458	10	11.7	0.855	6.53e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000307	0.000241
Ashkenazi Jewish	0.00	0.00
East Asian	0.00110	0.00109
Finnish	0.00	0.00
European (Non-Finnish)	0.000161	0.000149
Middle Eastern	0.00110	0.00109
South Asian	0.0000330	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:12665801, PubMed:17311996, PubMed:27743390). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (PubMed:12665801). This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling (PubMed:17311996). Appears to operate in a calcium-independent manner (PubMed:12665801). {ECO:0000269|PubMed:12665801, ECO:0000269|PubMed:17311996, ECO:0000269|PubMed:27743390}.
• Disease: DISEASE: Thrombocytopenia, anemia, and myelofibrosis (THAMY) [MIM:617441]: An autosomal recessive disorder characterized by thrombocytopenia, increased number of giant platelets, and anemia manifesting in early childhood. Bone marrow biopsy shows increased number of megakaryocytes and reticular fibrosis consistent with myelofibrosis. {ECO:0000269|PubMed:27743390}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.0690

Intolerance Scores

• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.21

Haploinsufficiency Scores

• pHI: 0.0722
• hipred: N
• hipred_score: 0.180
• ghis: 0.441

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Mpig6b
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: integrin-mediated signaling pathway;blood coagulation;negative regulation of signal transduction;platelet activation;erythrocyte differentiation;megakaryocyte differentiation;platelet formation;megakaryocyte development
• Cellular component: endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of membrane
• Molecular function: protein binding;heparin binding