PORCN

porcupine O-acyltransferase, the group of Membrane bound O-acyltransferase family

Basic information

Region (hg38): X:48508959-48520814

Previous symbols: [ "DHOF" ]

Links

ENSG00000102312NCBI:64840OMIM:300651HGNC:17652Uniprot:Q9H237AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • focal dermal hypoplasia (Strong), mode of inheritance: XL
  • focal dermal hypoplasia (Definitive), mode of inheritance: XL
  • focal dermal hypoplasia (Supportive), mode of inheritance: XL
  • microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD
  • focal dermal hypoplasia (Definitive), mode of inheritance: XL
  • focal dermal hypoplasia (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Focal dermal hypoplasiaXLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingAudiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic13948891; 1190805; 843447; 17546031; 17546030; 18325042; 19309688; 19863546; 19586929; 20420028; 21332693; 21472892; 21484999; 21732017; 22414489; 22250236; 22735390; 23131169; 23399492

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PORCN gene.

  • not_provided (116 variants)
  • Focal_dermal_hypoplasia (44 variants)
  • Inborn_genetic_diseases (36 variants)
  • PORCN-related_disorder (12 variants)
  • not_specified (5 variants)
  • History_of_neurodevelopmental_disorder (1 variants)
  • Genetic_developmental_and_epileptic_encephalopathy (1 variants)
  • Anophthalmia-microphthalmia_syndrome (1 variants)
  • Global_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PORCN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000203475.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
19
clinvar
9
clinvar
30
missense
5
clinvar
13
clinvar
63
clinvar
16
clinvar
1
clinvar
98
nonsense
14
clinvar
2
clinvar
16
start loss
1
1
frameshift
10
clinvar
4
clinvar
1
clinvar
15
splice donor/acceptor (+/-2bp)
6
clinvar
4
clinvar
1
clinvar
11
Total 35 26 65 35 10
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PORCNprotein_codingprotein_codingENST00000326194 1411853
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.00046800000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.371122080.5380.00001862975
Missense in Polyphen2874.7710.374481087
Synonymous2.276188.20.6920.00000798953
Loss of Function4.35022.10.000.00000175293

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1), to Wnt proteins. Serine palmitoleylation of WNT proteins is required for efficient binding to frizzled receptors. {ECO:0000250|UniProtKB:Q9JJJ7, ECO:0000269|PubMed:12034504, ECO:0000269|PubMed:20826466, ECO:0000269|PubMed:24292069}.;
Pathway
Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway;Disease;Signaling by WNT;Signal Transduction;WNT ligand biogenesis and trafficking;WNT ligand secretion is abrogated by the PORCN inhibitor LGK974;Signaling by WNT in cancer;Diseases of signal transduction (Consensus)

Recessive Scores

pRec
0.290

Intolerance Scores

loftool
rvis_EVS
-0.52
rvis_percentile_EVS
21.2

Haploinsufficiency Scores

pHI
0.303
hipred
Y
hipred_score
0.775
ghis
0.478

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.238

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Porcn
Phenotype
normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype;

Zebrafish Information Network

Gene name
porcn
Affected structure
neural tube
Phenotype tag
abnormal
Phenotype quality
shortened

Gene ontology

Biological process
protein lipidation;glycoprotein metabolic process;Wnt signaling pathway;protein palmitoleylation;canonical Wnt signaling pathway;regulation of postsynaptic membrane neurotransmitter receptor levels
Cellular component
endoplasmic reticulum;endoplasmic reticulum membrane;integral component of endoplasmic reticulum membrane;AMPA glutamate receptor complex;glutamatergic synapse
Molecular function
Wnt-protein binding;palmitoleoyltransferase activity