PLEKHM2

pleckstrin homology and RUN domain containing M2, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 1:15684319-15734769

Links

ENSG00000116786 ∙ NCBI:23207 ∙ OMIM:609613 ∙ HGNC:29131 ∙ Uniprot:Q8IWE5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dilated cardiomyopathy (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLEKHM2 gene.

• Dilated Cardiomyopathy, Recessive (639 variants)
• not provided (51 variants)
• Inborn genetic diseases (40 variants)
• PLEKHM2-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHM2 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			4	166	14	184
missense			313	7	10	330
nonsense			3			3
start loss						0
frameshift			7			7
inframe indel			8			8
splice donor/acceptor (+/-2bp)			2			2
splice region			11	19	9	39
non coding			3	72	47	122
Total	0	0	340	245	71

Variants in PLEKHM2

This is a list of pathogenic ClinVar variants found in the PLEKHM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-15684398-C-T			Benign (Jun 01, 2021)
1-15684510-G-GGGC			Benign (Apr 03, 2021)
1-15684564-G-A		Dilated Cardiomyopathy, Recessive	Likely benign (Aug 09, 2022)
1-15684566-C-T		Dilated Cardiomyopathy, Recessive • not specified	Uncertain significance (Nov 02, 2023)
1-15684572-A-T		Dilated Cardiomyopathy, Recessive	Uncertain significance (Mar 19, 2022)
1-15684580-G-A		Dilated Cardiomyopathy, Recessive	Uncertain significance (Nov 24, 2023)
1-15684583-C-G		Dilated Cardiomyopathy, Recessive	Uncertain significance (Dec 17, 2021)
1-15684588-C-T		Dilated Cardiomyopathy, Recessive	Likely benign (May 27, 2022)
1-15684608-C-T		Dilated Cardiomyopathy, Recessive	Uncertain significance (Jul 05, 2022)
1-15684609-G-A		Dilated Cardiomyopathy, Recessive	Likely benign (Jan 09, 2024)
1-15684611-TGAA-T		Dilated Cardiomyopathy, Recessive	Uncertain significance (Apr 23, 2022)
1-15684632-C-T		Dilated Cardiomyopathy, Recessive	Likely benign (Jan 08, 2024)
1-15684636-C-T		Dilated Cardiomyopathy, Recessive	Likely benign (Sep 14, 2022)
1-15684697-G-GGCGACCCTGCTGCCGCAGGGACTC			Benign (Aug 03, 2020)
1-15715894-T-C			Benign (Oct 30, 2018)
1-15716217-G-GGT		Dilated Cardiomyopathy, Recessive	Likely benign (Dec 09, 2023)
1-15716219-T-C		Dilated Cardiomyopathy, Recessive	Likely benign (Sep 08, 2021)
1-15716220-G-C		Dilated Cardiomyopathy, Recessive	Likely benign (Sep 22, 2023)
1-15716220-GT-G		Dilated Cardiomyopathy, Recessive	Benign (Sep 18, 2023)
1-15716220-G-GT		Dilated Cardiomyopathy, Recessive	Benign (Jun 19, 2023)
1-15716221-T-G		Dilated Cardiomyopathy, Recessive	Likely benign (Jan 12, 2024)
1-15716222-T-G		Dilated Cardiomyopathy, Recessive	Likely benign (Apr 26, 2022)
1-15716227-T-C		Dilated Cardiomyopathy, Recessive	Likely benign (Jul 24, 2020)
1-15716228-TTC-T		Dilated Cardiomyopathy, Recessive	Benign (Jan 31, 2024)
1-15716229-TC-T		Dilated Cardiomyopathy, Recessive	Benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLEKHM2	protein_coding	protein_coding	ENST00000375799	20	50438

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000171	1.00	124661	0	23	124684	0.0000922

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.00	467	606	0.771	0.0000382	6513
Missense in Polyphen		130	188.76	0.68869		2055
Synonymous	-0.0573	270	269	1.00	0.0000192	1985
Loss of Function	4.07	17	47.2	0.360	0.00000233	543

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.000203	0.000199
East Asian	0.000228	0.000222
Finnish	0.00	0.00
European (Non-Finnish)	0.0000912	0.0000884
Middle Eastern	0.000228	0.000222
South Asian	0.0000327	0.0000327
Other	0.000184	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in the regulation of conventional kinesin activity. Required for maintenance of the Golgi apparatus organization. May play a role in membrane tubulation (PubMed:15905402). May play a role in lysosomes movement and localization at the cell periphery (PubMed:25898167). {ECO:0000269|PubMed:15905402, ECO:0000269|PubMed:25898167}.
• Pathway: Salmonella infection - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.449
• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.01

Haploinsufficiency Scores

• pHI: 0.219
• hipred: N
• hipred_score: 0.414
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.375

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plekhm2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system 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); immune system phenotype

Gene ontology

• Biological process: Golgi organization;lysosome localization;regulation of protein localization;positive regulation of membrane tubulation
• Cellular component: endosome membrane
• Molecular function: protein binding;kinesin binding