GPC1

Chr 2

glypican 1

Also known as: glypican

NCBI Gene: 2817 ENSG00000063660 UniProt: P35052 OMIM: 600395

The GPC1 protein is a cell surface heparan sulfate proteoglycan that binds collagen, participates in Schwann cell myelination, and regulates skeletal muscle differentiation by sequestering FGF2 signaling. Mutations cause autosomal recessive omodysplasia types 1 and 2, characterized by congenital limb malformations and facial dysmorphism. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

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

0.62

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.016

Z-score 2.87

OE 0.33 (0.19–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.33Z-score

OE missense 0.95 (0.87–1.04)

346 obs / 363.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.19–0.62)

0≤0.351.4

Missense OE?0.95 (0.87–1.04)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 7 / 21.3Missense obs/exp: 346 / 363.9Syn Z: -0.65

Background carrier burden — how many people carry a rare variant somewhere in GPC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

840 rare PASS variants

Rare truncating (LoF)

1 in 2,300

72 rare PASS variants

Rare synonymous (reference)

1 in 68

402 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPC1. 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 56	1 in 1,700
South Asian	~43k	1 in 52	1 in 4,000
Remaining (unassigned)	~30k	1 in 46	1 in 800
European (Finnish)	~26k	1 in 110	≈ 1 in 5,500
Admixed American	~22k	1 in 56	1 in 3,600
African / African American	~21k	1 in 70	1 in 2,400
East Asian	~20k	1 in 64	≈ 1 in 5,600
Ashkenazi Jewish	~13k	1 in 190	none seen
Middle Eastern	~2,884	1 in 66	≈ 1 in 790

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.