GPC6

Chr 13

glypican 6

Also known as: OMIMD1

NCBI Gene: 10082 ENSG00000183098 UniProt: Q9Y625

The protein is a cell surface heparan sulfate proteoglycan that functions as a coreceptor for growth factors, extracellular matrix proteins, and proteases. Mutations cause omodysplasia 1, a skeletal dysplasia characterized by limb shortening and facial dysmorphism. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOmodysplasia 1

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.142

Z-score 3.31

OE 0.26 (0.14–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.90Z-score

OE missense 0.86 (0.78–0.95)

276 obs / 321.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.51)

0≤0.351.4

Missense OE?0.86 (0.78–0.95)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 6 / 23.2Missense obs/exp: 276 / 321.5Syn Z: -1.17

Background carrier burden — how many people carry a rare variant somewhere in GPC6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

694 rare PASS variants

Rare truncating (LoF)

1 in 7,200

45 rare PASS variants

Rare synonymous (reference)

1 in 240

297 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPC6. 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)	~556k	1 in 120	1 in 10,000
South Asian	~43k	1 in 64	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 91	1 in 6,000
European (Finnish)	~27k	1 in 240	1 in 3,300
Admixed American	~22k	1 in 88	≈ 1 in 5,600
African / African American	~21k	1 in 100	≈ 1 in 6,900
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 72	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.