GPC5

Chr 13

glypican 5

NCBI Gene: 2262 ENSG00000179399 UniProt: P78333

GPC5 encodes a cell surface proteoglycan that bears heparan sulfate and is anchored to the membrane via a glycosyl phosphatidylinositol linkage. Mutations cause Simpson-Golabi-Behmel syndrome type 2, an X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, intellectual disability, and distinctive facial features. The gene shows extreme intolerance to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.24

OE 0.73 (0.50–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.59Z-score

OE missense 1.09 (1.00–1.19)

351 obs / 321.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.50–1.08)

0≤0.351.4

Missense OE?1.09 (1.00–1.19)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 18 / 24.6Missense obs/exp: 351 / 321.3Syn Z: -1.44

Background carrier burden — how many people carry a rare variant somewhere in GPC5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

800 rare PASS variants

Rare truncating (LoF)

1 in 1,000

118 rare PASS variants

Rare synonymous (reference)

1 in 130

303 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPC5. 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 98	1 in 1,100
South Asian	~43k	1 in 59	1 in 750
Remaining (unassigned)	~30k	1 in 62	1 in 700
European (Finnish)	~27k	1 in 230	≈ 1 in 12,000
Admixed American	~22k	1 in 69	1 in 520
African / African American	~21k	1 in 47	1 in 710
East Asian	~20k	1 in 130	1 in 2,400
Ashkenazi Jewish	~13k	1 in 180	1 in 2,100
Middle Eastern	~2,884	1 in 62	≈ 1 in 1,400

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.