MPIG6B

Chr 6AR

megakaryocyte and platelet inhibitory receptor G6b

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

NCBI Gene: 80739ENSG00000204420UniProt: O95866

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]

Primary Disease Associations & Inheritance

?Thrombocytopenia, anemia, and myelofibrosisMIM #617441
AR
49
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MPIG6B
🧬
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.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 20 VUS of 49 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.45LOEUF
pLI 0.000
Z-score 0.46
OE 0.86 (0.53–1.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.04Z-score
OE missense 0.77 (0.67–0.89)
126 obs / 163.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.86 (0.53–1.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.67–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.76
0≤1.21.6
LoF obs/exp: 10 / 11.7Missense obs/exp: 126 / 163.4Syn Z: 1.65

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic8
VUS20
Likely Benign9
Benign3
9
Pathogenic
8
Likely Pathogenic
20
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
7
0
9
Likely Pathogenic
3
0
3
2
8
VUS
0
16
4
0
20
Likely Benign
0
5
0
4
9
Benign
0
1
0
2
3
Total52214849

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

View in ClinVar →

Protein Context — Lollipop Plot

MPIG6B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Thrombocytopenia, anemia, and myelofibrosis

MIM #617441

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Thrombocytopenia in myelofibrosis is characterized by inflammatory megakaryocytes with reduced G6B expression.
Varricchio L et al.·Blood
2025Clinical trial
Comprehensive analysis of serum exosome-derived lncRNAs and mRNAs from patients with rheumatoid arthritis.
Xue L et al.·Arthritis Res Ther
2023Cohort
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Zhang Y et al.·Front Immunol
2024
A novel MPIG6B gene mutation in an adolescent girl with congenital thrombocytopenia and myelofibrosis.
Wang Z et al.·Curr Res Transl Med
2022Case report
Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles.
Hu L et al.·J Extracell Vesicles
2024
Case report of a novel MPIG6B gene mutation in a Chinese boy with pancytopenia and splenomegaly.
Chen H et al.·Gene
2019Case report
Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential.
Cheung S et al.·J Assist Reprod Genet
2024
Molecular characterization of triple-negative myeloproliferative neoplasms by next-generation sequencing.
Maddali M et al.·Ann Hematol
2022Case report
Congenital macrothrombocytopenia with focal myelofibrosis due to mutations in human G6b-B is rescued in humanized mice.
Hofmann I et al.·Blood
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools