GPC4

Chr XXLR

glypican 4

Also known as: K-glypican, KPTS

NCBI Gene: 2239ENSG00000076716UniProt: O75487OMIM: 300168

GPC4 encodes a cell surface heparan sulfate proteoglycan that is involved in kidney tubule and central nervous system development. Mutations cause Keipert syndrome, an X-linked recessive disorder. The gene is highly constrained against loss-of-function mutations (pLI 0.93, LOEUF 0.37), indicating it is intolerant to inactivating variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.371 OMIM phenotype
Clinical Summary— GPC4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 43 VUS of 231 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.926
Z-score 3.39
OE 0.12 (0.05–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.66Z-score
OE missense 0.69 (0.61–0.79)
159 obs / 229.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.05–0.37)
0≤0.351.4
Missense OE0.69 (0.61–0.79)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 2 / 17.1Missense obs/exp: 159 / 229.6Syn Z: 0.55

ClinVar Variant Classifications

231 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic7
VUS43
Likely Benign11
Benign8
Conflicting1
71
Pathogenic
7
Likely Pathogenic
43
VUS
11
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
65
0
71
Likely Pathogenic
4
0
3
0
7
VUS
0
31
12
0
43
Likely Benign
0
3
3
5
11
Benign
0
2
6
0
8
Conflicting
—1
Total1036895141

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

View in ClinVar →

Protein Context — Lollipop Plot

GPC4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients