PLEKHN1

pleckstrin homology domain containing N1, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 1:966482-975865

Links

ENSG00000187583 ∙ NCBI:84069 ∙ ∙ HGNC:25284 ∙ Uniprot:Q494U1 ∙ 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 PLEKHN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHN1 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				1		1
missense			98	22	4	124
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	98	23	4

Variants in PLEKHN1

This is a list of pathogenic ClinVar variants found in the PLEKHN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-966542-G-A			Benign (Apr 10, 2018)
1-966543-C-A			Benign (Apr 10, 2018)
1-966554-C-T		not specified	Uncertain significance (Dec 28, 2022)
1-966562-C-T		not specified	Uncertain significance (Jan 30, 2025)
1-966574-C-T		not specified	Uncertain significance (Aug 04, 2023)
1-966575-G-C		not specified	Uncertain significance (Sep 09, 2024)
1-966584-T-C		not specified	Uncertain significance (Feb 13, 2025)
1-966717-C-T		not specified	Uncertain significance (Apr 20, 2023)
1-966718-G-A		not specified	Uncertain significance (Jan 08, 2024)
1-966724-C-T		not specified	Likely benign (Jul 08, 2022)
1-966729-G-A		not specified	Uncertain significance (Feb 28, 2024)
1-966744-G-A		not specified	Uncertain significance (Nov 13, 2023)
1-966753-C-G		not specified	Likely benign (Dec 06, 2024)
1-966771-G-A		not specified	Uncertain significance (Nov 09, 2024)
1-966780-C-G		not specified	Uncertain significance (Aug 16, 2022)
1-966787-A-C		not specified	Uncertain significance (Sep 09, 2024)
1-966795-C-T		not specified	Uncertain significance (Oct 28, 2024)
1-966796-C-T		not specified	Uncertain significance (Jun 09, 2022)
1-970310-C-A		not specified	Uncertain significance (Jun 04, 2024)
1-970326-T-C		not specified	Uncertain significance (Mar 01, 2025)
1-970328-A-C		not specified	Uncertain significance (Jan 09, 2024)
1-970349-C-T		not specified	Uncertain significance (May 10, 2022)
1-970389-A-G		not specified	Uncertain significance (May 25, 2022)
1-970514-C-T			Benign/Likely benign (Jan 01, 2023)
1-970521-G-A		not specified	Uncertain significance (Oct 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLEKHN1	protein_coding	protein_coding	ENST00000379410	16	9369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-14	0.149	125455	1	177	125633	0.000709

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.80	480	381	1.26	0.0000241	3802
Missense in Polyphen		135	97.727	1.3814		1147
Synonymous	-2.47	216	175	1.24	0.0000114	1323
Loss of Function	1.01	25	31.1	0.805	0.00000157	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00292	0.00280
Ashkenazi Jewish	0.000109	0.0000994
East Asian	0.000285	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000585	0.000511
Middle Eastern	0.000285	0.000272
South Asian	0.00286	0.00199
Other	0.000738	0.000653

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Controls the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR, in cooperation with the RNA stabilizer ELAVL1 (PubMed:29180010). Decreases the stability of the leptin mRNA by antagonizing the function of ELAVL1 by inducing its atypical recruitment from the nucleus to the cytosol (By similarity). Binds to cardiolipin (CL), phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidylserine (PS) (PubMed:18191643). Promotes apoptosis by enhancing BAX-BAK hetro-oligomerization via interaction with BID in colon cancer cells (PubMed:29531808) (By similarity). {ECO:0000250|UniProtKB:Q8C886, ECO:0000269|PubMed:18191643, ECO:0000269|PubMed:29180010, ECO:0000269|PubMed:29531808}.
• Pathway: EGFR1 (Consensus)

Recessive Scores

• pRec: 0.0962

Intolerance Scores

• loftool: 0.926
• rvis_EVS: 0.9
• rvis_percentile_EVS: 89.33

Haploinsufficiency Scores

• pHI: 0.199
• hipred: N
• hipred_score: 0.146
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.259

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plekhn1

Gene ontology

• Biological process: response to hypoxia;positive regulation of apoptotic process;3'-UTR-mediated mRNA destabilization
• Cellular component: mitochondrion;cytoskeleton;plasma membrane;mitochondrial membrane
• Molecular function: phosphatidylserine binding;protein binding;phosphatidic acid binding;cardiolipin binding;phosphatidylinositol phosphate binding