PENK

proenkephalin, the group of Neuropeptides

Basic information

Region (hg38): 8:56436673-56446671

Links

ENSG00000181195 ∙ NCBI:5179 ∙ OMIM:131330 ∙ HGNC:8831 ∙ Uniprot:P01210 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (19 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PENK 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				2	4	6
missense			18	2	1	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	18	5	5

Variants in PENK

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

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

Position	Type	Phenotype	Significance	ClinVar
8-56441293-G-A			Benign (Jul 23, 2018)
8-56441319-C-T		not specified	Uncertain significance (Nov 30, 2021)
8-56441343-C-T		not specified	Uncertain significance (Dec 06, 2021)
8-56441347-G-A			Benign (Jul 23, 2018)
8-56441388-A-C		not specified	Uncertain significance (Dec 09, 2023)
8-56441390-C-A		not specified	Uncertain significance (Feb 15, 2023)
8-56441420-C-T		not specified	Uncertain significance (Aug 02, 2021)
8-56441421-G-C		not specified	Uncertain significance (Jan 24, 2024)
8-56441429-C-T			Likely benign (Aug 15, 2017)
8-56441464-T-G		not specified	Uncertain significance (Mar 01, 2024)
8-56441508-T-C		not specified	Uncertain significance (Feb 12, 2024)
8-56441532-C-G		not specified	Uncertain significance (Jul 09, 2021)
8-56441556-C-T		not specified	Uncertain significance (Feb 10, 2023)
8-56441568-T-C		not specified	Likely benign (May 10, 2022)
8-56441576-C-T		not specified	Uncertain significance (Mar 02, 2023)
8-56441666-C-G		not specified	Uncertain significance (Oct 06, 2022)
8-56441672-C-T		not specified	Uncertain significance (Jan 11, 2023)
8-56441679-C-T		not specified	Uncertain significance (Dec 21, 2023)
8-56441700-C-T		not specified	Uncertain significance (Oct 20, 2021)
8-56441736-T-C		not specified	Uncertain significance (Jan 11, 2023)
8-56441797-G-T		not specified	Uncertain significance (Mar 17, 2023)
8-56441815-A-G			Likely benign (Jun 11, 2018)
8-56441821-T-C			Benign (Aug 21, 2018)
8-56441828-G-T			Benign (Jul 23, 2018)
8-56441865-G-C		not specified	Uncertain significance (Jul 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PENK	protein_coding	protein_coding	ENST00000314922	2	10061

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000208	0.747	125653	0	95	125748	0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.725	179	154	1.16	0.00000853	1756
Missense in Polyphen		57	50.235	1.1347		558
Synonymous	0.400	58	62.0	0.935	0.00000346	498
Loss of Function	1.01	7	10.5	0.665	6.25e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00133	0.00133
Ashkenazi Jewish	0.00218	0.00218
East Asian	0.000218	0.000217
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.000218	0.000217
South Asian	0.000294	0.000294
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Met- and Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress. PENK(114-133) and PENK(237-258) increase glutamate release in the striatum. PENK(114-133) decreases GABA concentration in the striatum.
• Pathway: Signaling by GPCR;Signal Transduction;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);G alpha (i) signalling events;GPCR downstream signalling;AP-1 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.375

Intolerance Scores

• loftool: 0.826
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.182
• hipred: N
• hipred_score: 0.342
• ghis: 0.422

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.506

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Penk
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); 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; limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: osteoblast differentiation;behavioral fear response;response to hypoxia;startle response;aggressive behavior;signal transduction;G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;chemical synaptic transmission;aging;response to radiation;regulation of signaling receptor activity;glial cell proliferation;sensory perception of pain;response to estradiol;response to lipopolysaccharide;cellular response to oxidative stress;response to nicotine;locomotory exploration behavior;response to morphine;post-translational protein modification;cellular protein metabolic process;response to ethanol;response to calcium ion;general adaptation syndrome, behavioral process;cellular response to vitamin D;cellular response to cAMP;cellular response to transforming growth factor beta stimulus;response to epinephrine;cellular response to virus;positive regulation of behavioral fear response
• Cellular component: extracellular region;endoplasmic reticulum lumen;plasma membrane;dendrite;symmetric synapse;synaptic vesicle lumen;neuronal cell body;perikaryon;axon terminus;cell body fiber;neuronal dense core vesicle lumen
• Molecular function: opioid peptide activity;neuropeptide hormone activity;opioid receptor binding