PORCN

Chr XXLD

porcupine O-acyltransferase

Also known as: DHOF, FODH, MG61, PORC, PPN

NCBI Gene: 64840ENSG00000102312UniProt: Q9H237

This gene belongs to the evolutionarily conserved porcupine (Porc) gene family. Genes of the porcupine family encode endoplasmic reticulum proteins with multiple transmembrane domains. Porcupine proteins are involved in the processing of Wnt (wingless and int homologue) proteins. Disruption of this gene is associated with focal dermal hypoplasia, and the encoded protein has been implicated in cancer. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

Focal dermal hypoplasiaMIM #305600
XLD
1
Active trials
122
Pathogenic / LP
238
ClinVar variants
27
Pubs (1 yr)
2.4
Missense Z
0.14
LOEUF· LoF intolerant
Clinical Summary— PORCN
🧬
Gene-Disease Validity (ClinGen)
focal dermal hypoplasia · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
122 Pathogenic / Likely Pathogenic· 59 VUS of 238 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — PORCN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 4.35
OE 0.00 (0.00–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.37Z-score
OE missense 0.54 (0.46–0.63)
112 obs / 208.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.14)
0≤0.351.4
Missense OE0.54 (0.46–0.63)
0≤0.61.4
Synonymous OE0.69
0≤1.21.6
LoF obs/exp: 0 / 22.1Missense obs/exp: 112 / 208.3Syn Z: 2.27

ClinVar Variant Classifications

238 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic104
Likely Pathogenic18
VUS59
Likely Benign34
Benign14
Conflicting9
104
Pathogenic
18
Likely Pathogenic
59
VUS
34
Likely Benign
14
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
4
89
0
104
Likely Pathogenic
8
6
4
0
18
VUS
2
49
8
0
59
Likely Benign
0
11
8
15
34
Benign
0
1
8
5
14
Conflicting
—9
Total217111720238

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

View in ClinVar →

PORCN · protein map & ClinVar variants

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

Gene2Phenotype Curations

PORCN-related focal dermal hypoplasia

definitive
Monoallelic X HeterozygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
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