PORCN

Chr X

porcupine O-acyltransferase

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

NCBI Gene: 64840 ENSG00000102312 UniProt: Q9H237

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.14

Clinical Summary— PORCN

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Gene-Disease Validity (ClinGen)

focal dermal hypoplasia · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

57 unique Pathogenic / Likely Pathogenic· 72 VUS of 255 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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GeneReview available — PORCN

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 503

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 OE?0.00 (0.00–0.14)

0≤0.351.4

Missense OE?0.54 (0.46–0.63)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 0 / 22.1Missense obs/exp: 112 / 208.3Syn Z: 2.27

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33

Likely Pathogenic24

VUS72

Likely Benign45

Benign17

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	28	4	1	0	33
Likely Pathogenic	15	8	0	1	24
VUS	1	66	4	1	72
Likely Benign	0	16	8	21	45
Benign	0	1	9	7	17
Conflicting	—				7
Total	44	95	22	30	198

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

View in ClinVar →

84 pathogenic / likely-pathogenic (of 92) ClinVar copy-number / structural variants overlap PORCN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →