GPM6B

Chr X

glycoprotein M6B

Also known as: M6B

NCBI Gene: 2824 ENSG00000046653 UniProt: Q13491 OMIM: 300051

This gene encodes a membrane glycoprotein involved in neural development and regulation of osteoblast function and bone formation. Mutations cause autosomal recessive intellectual disability with seizures and behavioral abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), affecting both neurological and skeletal systems.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.59

Clinical Summary— GPM6B

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

21 VUS of 101 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.346

Z-score 2.58

OE 0.23 (0.10–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.99Z-score

OE missense 0.51 (0.42–0.63)

68 obs / 132.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.10–0.59)

0≤0.351.4

Missense OE?0.51 (0.42–0.63)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 3 / 13.1Missense obs/exp: 68 / 132.4Syn Z: -0.41

This gene — mechanism propensity

0.5968th %ile

GOF

0.77top 25%

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

101 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	21	0	0	21
Likely Benign	1	1	1	3
Benign	0	0	1	1
Total	22	1	2	25

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

View in ClinVar →

86 pathogenic / likely-pathogenic (of 99) ClinVar copy-number / structural variants overlap GPM6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →