PORCN

Chr XXLD

porcupine O-acyltransferase

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

NCBI Gene: 64840ENSG00000102312UniProt: Q9H237OMIM: 300651

The PORCN protein is a palmitoleoyltransferase that attaches fatty acids to Wnt proteins, which is essential for efficient Wnt signaling pathway function. Mutations cause focal dermal hypoplasia, an X-linked dominant condition affecting skin, skeletal, dental, and ocular development. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.135), indicating that such variants are likely pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLDLOEUF 0.141 OMIM phenotype
Clinical Summary— PORCN
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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.
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ClinVar Variants
141 unique Pathogenic / Likely Pathogenic· 79 VUS of 346 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
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

346 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic26
VUS79
Likely Benign45
Benign17
Conflicting7
115
Pathogenic
26
Likely Pathogenic
79
VUS
45
Likely Benign
17
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
4
83
0
115
Likely Pathogenic
15
8
2
1
26
VUS
1
65
12
1
79
Likely Benign
0
16
8
21
45
Benign
0
1
9
7
17
Conflicting
—7
Total449411430289

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

View in ClinVar →

Protein Context — Lollipop Plot

PORCN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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