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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

GOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in GPM6B?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 560

226 rare PASS variants

Rare truncating (LoF)

1 in 10,000

16 rare PASS variants

Rare synonymous (reference)

1 in 450

140 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPM6B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 630	1 in 11,000
South Asian	~36k	1 in 440	1 in 1,800
Remaining (unassigned)	~31k	1 in 270	none seen
European (Finnish)	~27k	≈ 1 in 6,700	≈ 1 in 27,000
Admixed American	~23k	1 in 490	none seen
African / African American	~21k	1 in 230	≈ 1 in 4,700
East Asian	~20k	1 in 450	none seen
Ashkenazi Jewish	~13k	≈ 1 in 4,300	≈ 1 in 13,000
Middle Eastern	~2,758	1 in 460	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓