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 (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

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 (16 variants)
• Focal dermal hypoplasia (13 variants)
• Inborn genetic diseases (3 variants)
• Global developmental delay (1 variants)
• PORCN-related disorder (1 variants)
• Focal dermal hypoplasia;Anophthalmia-microphthalmia syndrome (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	7	20
missense	6	8	44	13	1	72
nonsense	12	1				13
start loss		1				1
frameshift	3	1				4
inframe indel		3				3
splice donor/acceptor (+/-2bp)	5	1	1			7
splice region		1	1	5		7
non coding			1	4	8	13
Total	26	15	46	30	16

Variants in PORCN

This is a list of pathogenic ClinVar variants found in the PORCN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-48509772-CTGCTTTGACAGA-C			Likely pathogenic (May 24, 2024)
X-48509815-TCTGCAATGGCCACCTTTAGCCGCCAGGAA-CCACC		Focal dermal hypoplasia	Likely pathogenic (Dec 17, 2024)
X-48509829-C-T		Inborn genetic diseases	Likely benign (Feb 13, 2020)
X-48509837-G-A			Uncertain significance (Oct 16, 2024)
X-48509841-G-A			Likely benign (Feb 28, 2022)
X-48509844-A-G		Inborn genetic diseases	Likely benign (Mar 29, 2017)
X-48509868-CTGTCTCCTGCCTACTGCCCAGCAGGGCCTTGA-C		Focal dermal hypoplasia	Pathogenic (May 31, 2019)
X-48509869-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2016)
X-48509880-T-A			Likely benign (May 26, 2023)
X-48509886-C-G			Likely benign (Jul 29, 2022)
X-48509898-T-C			Likely benign (Dec 25, 2022)
X-48509902-C-T		Focal dermal hypoplasia	Pathogenic (Oct 01, 2019)
X-48509932-G-A		Inborn genetic diseases	Likely benign (Mar 29, 2023)
X-48509939-G-T			Uncertain significance (Jun 01, 2021)
X-48509942-T-A		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
X-48509956-G-A			Uncertain significance (Feb 11, 2022)
X-48509963-G-A			Likely benign (Sep 01, 2018)
X-48511048-C-T			Likely benign (Mar 09, 2019)
X-48511205-T-C			Benign (Oct 07, 2019)
X-48511294-G-C		Focal dermal hypoplasia	Pathogenic (-)
X-48511327-G-A			Likely benign (Oct 24, 2021)
X-48511336-G-A		Focal dermal hypoplasia • Focal dermal hypoplasia;Anophthalmia-microphthalmia syndrome	Pathogenic (Feb 03, 2022)
X-48511351-T-A			Uncertain significance (May 26, 2021)
X-48511359-C-A			Uncertain significance (Jun 03, 2024)
X-48511380-G-A		Focal dermal hypoplasia	Pathogenic (Dec 13, 2022)

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
1.00	0.000468	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

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

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

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