PORCN

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

Basic information

Region (hg38): X:48508959-48520814

Previous symbols: [ "DHOF" ]

Links

ENSG00000102312 ∙ NCBI:64840 ∙ OMIM:300651 ∙ HGNC:17652 ∙ Uniprot:Q9H237 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• focal dermal hypoplasia (Definitive), mode of inheritance: XL
• focal dermal hypoplasia (Definitive), mode of inheritance: XL
• focal dermal hypoplasia (Strong), 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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal dermal hypoplasia	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	13948891; 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 (125 variants)
• Focal_dermal_hypoplasia (49 variants)
• Inborn_genetic_diseases (40 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		2	7	22	9	40
missense	5	14	91	17	1	128
nonsense	14	2	3			19
start loss		1				1
frameshift	11	4	1			16
splice donor/acceptor (+/-2bp)	7	5	13			25
Total	37	28	115	39	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PORCN	protein_coding	protein_coding	ENST00000326194	14	11853

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	112	208	0.538	0.0000186	2975
Missense in Polyphen		28	74.771	0.37448		1087
Synonymous	2.27	61	88.2	0.692	0.00000798	953
Loss of Function	4.35	0	22.1	0.00	0.00000175	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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