MPIG6B

Chr 6AR

megakaryocyte and platelet inhibitory receptor G6b

Also known as: C6orf25, G6b, G6b-B, NG31, THAMY

This gene is a member of the immunoglobulin (Ig) superfamily and is located in the major histocompatibility complex (MHC) class III region. The protein encoded by this gene is a glycosylated, plasma membrane-bound cell surface receptor, but soluble isoforms encoded by some transcript variants have been found in the endoplasmic reticulum and Golgi before being secreted. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 1.451 OMIM phenotype
Clinical SummaryMPIG6B
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Gene-Disease Validity (ClinGen)
thrombocytopenia, anemia, and myelofibrosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 16 VUS of 44 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.45LOEUF
pLI 0.000
Z-score 0.46
OE 0.86 (0.531.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
1.04Z-score
OE missense 0.77 (0.670.89)
126 obs / 163.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.86 (0.531.45)
00.351.4
Missense OE?0.77 (0.670.89)
00.61.4
Synonymous OE?0.76
01.21.6
LoF obs/exp: 10 / 11.7Missense obs/exp: 126 / 163.4Syn Z: 1.65

This gene — mechanism propensity

DN
0.6745th %ile
GOF
0.7029th %ile
LOF
0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

44 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic6
VUS16
Likely Benign9
Benign3
4
Pathogenic
6
Likely Pathogenic
16
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
0
0
4
Likely Pathogenic
6
0
0
0
6
VUS
1
15
0
0
16
Likely Benign
0
5
0
4
9
Benign
0
1
0
2
3
Total11210638

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

7 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap MPIG6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MPIG6B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →