PLEKHM1
Basic information
Region (hg38): 17:45435900-45490758
Links
Phenotypes
GenCC
Source:
- osteopetrosis, autosomal dominant 3 (Limited), mode of inheritance: AD
- autosomal recessive osteopetrosis 6 (Limited), mode of inheritance: AR
- autosomal recessive osteopetrosis 6 (Supportive), mode of inheritance: AR
- osteopetrosis, autosomal dominant 3 (Limited), mode of inheritance: Unknown
- osteopetrosis, autosomal dominant 3 (Limited), mode of inheritance: AD
- autosomal recessive osteopetrosis 6 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Osteopetrosis, autosomal dominant 3; Osteopetrosis, autosomal recessive 6 | AD/AR | 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 | Musculoskeletal | 17404618; 17997709; 27291868 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (142 variants)
- not_provided (8 variants)
- Osteopetrosis,_autosomal_dominant_3 (6 variants)
- Autosomal_recessive_osteopetrosis_6 (3 variants)
- Autosomal_recessive_osteopetrosis_1 (1 variants)
- Increased_bone_mineral_density (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014798.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 4 | |||||
missense | 135 | 10 | 146 | |||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
Total | 3 | 1 | 137 | 12 | 1 |
Highest pathogenic variant AF is 0.00000185892
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PLEKHM1 | protein_coding | protein_coding | ENST00000430334 | 11 | 54850 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00814 | 0.992 | 125721 | 0 | 27 | 125748 | 0.000107 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.18 | 531 | 613 | 0.866 | 0.0000408 | 6850 |
Missense in Polyphen | 160 | 220.9 | 0.72431 | 2500 | ||
Synonymous | 0.781 | 259 | 275 | 0.940 | 0.0000188 | 2194 |
Loss of Function | 4.25 | 12 | 41.6 | 0.288 | 0.00000200 | 475 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000946 | 0.0000904 |
Ashkenazi Jewish | 0.000198 | 0.000198 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.000139 | 0.000139 |
European (Non-Finnish) | 0.000145 | 0.000141 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.0000980 | 0.0000980 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Proposed to act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Seems to be involved in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). Involved in bone resorption (By similarity). In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella- containing vacuole (SCV) probably in concert with the HOPS complex and Rab7 (PubMed:25500191). {ECO:0000250|UniProtKB:Q5PQS0, ECO:0000250|UniProtKB:Q7TSI1, ECO:0000269|PubMed:12820725, ECO:0000269|PubMed:20943950, ECO:0000269|PubMed:25498145, ECO:0000269|PubMed:25500191, ECO:0000305}.;
- Disease
- DISEASE: Osteopetrosis, autosomal recessive 6 (OPTB6) [MIM:611497]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. {ECO:0000269|PubMed:17404618}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- loftool
- 0.503
- rvis_EVS
- -1.53
- rvis_percentile_EVS
- 3.41
Haploinsufficiency Scores
- pHI
- 0.113
- hipred
- Y
- hipred_score
- 0.685
- ghis
- 0.490
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.745
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Plekhm1
- Phenotype
- hematopoietic system phenotype; normal phenotype; renal/urinary system phenotype; skeleton phenotype; immune system 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype;
Gene ontology
- Biological process
- autophagy;protein transport;lysosome localization;intracellular signal transduction;positive regulation of bone resorption;positive regulation of ruffle assembly
- Cellular component
- nucleolus;lysosomal membrane;endosome membrane;intracellular membrane-bounded organelle
- Molecular function
- metal ion binding