PDCD6IP
programmed cell death 6 interacting protein
Basic information
Region (hg38): 3:33798571-33869707
Links
Phenotypes
GenCC
Source:
- microcephaly 29, primary, autosomal recessive (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Microcephaly 29, primary, autosomal recessive | 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 | Craniofacial; Musculoskeletal; Neurologic | 32286682 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDCD6IP 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 | |||||
| missense | 30 | 32 | ||||
| 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 | 30 | 1 | 3 |
Variants in PDCD6IP
This is a list of pathogenic ClinVar variants found in the PDCD6IP region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-33798761-G-T | not specified | Uncertain significance (Aug 10, 2023) | ||
| 3-33798789-C-G | not specified | Uncertain significance (Apr 04, 2023) | ||
| 3-33798807-C-G | not specified | Uncertain significance (May 25, 2022) | ||
| 3-33798874-T-TGCGCC | Microcephaly 29, primary, autosomal recessive | Pathogenic (Oct 03, 2022) | ||
| 3-33798921-C-A | not specified | Uncertain significance (Dec 17, 2023) | ||
| 3-33812094-A-G | not specified | Uncertain significance (Jul 10, 2023) | ||
| 3-33825253-G-A | not specified | Uncertain significance (Jun 29, 2023) | ||
| 3-33825288-T-G | not specified | Uncertain significance (Jul 05, 2023) | ||
| 3-33825327-A-T | not specified | Uncertain significance (Jan 08, 2024) | ||
| 3-33826570-C-T | not specified | Uncertain significance (Oct 29, 2024) | ||
| 3-33836064-A-C | not specified | Uncertain significance (Sep 26, 2022) | ||
| 3-33836123-A-T | not specified | Uncertain significance (May 29, 2024) | ||
| 3-33836149-G-A | not specified | Uncertain significance (Oct 05, 2021) | ||
| 3-33836155-G-A | not specified | Uncertain significance (Dec 03, 2024) | ||
| 3-33838217-G-C | not specified | Uncertain significance (Oct 16, 2024) | ||
| 3-33838220-G-A | not specified | Uncertain significance (Dec 01, 2022) | ||
| 3-33841979-A-G | not specified | Uncertain significance (Feb 06, 2024) | ||
| 3-33841994-C-A | not specified | Uncertain significance (Jun 16, 2023) | ||
| 3-33841995-A-G | not specified | Uncertain significance (Mar 28, 2024) | ||
| 3-33842000-G-A | Benign (Dec 15, 2017) | |||
| 3-33844145-G-A | not specified | Uncertain significance (May 30, 2023) | ||
| 3-33844152-A-G | not specified | Uncertain significance (Nov 09, 2024) | ||
| 3-33844175-C-T | not specified | Uncertain significance (Nov 14, 2024) | ||
| 3-33845470-A-G | not specified | Uncertain significance (Mar 18, 2024) | ||
| 3-33852529-A-C | not specified | Uncertain significance (May 30, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PDCD6IP | protein_coding | protein_coding | ENST00000457054 | 18 | 71351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.706 | 0.294 | 125735 | 0 | 9 | 125744 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.976 | 393 | 451 | 0.871 | 0.0000220 | 5656 |
| Missense in Polyphen | 72 | 115.58 | 0.62293 | 1478 | ||
| Synonymous | -0.239 | 174 | 170 | 1.02 | 0.00000871 | 1694 |
| Loss of Function | 4.85 | 9 | 43.6 | 0.207 | 0.00000210 | 571 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000116 | 0.000109 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000452 | 0.0000440 |
| Middle Eastern | 0.000116 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000201 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17853893, PubMed:17556548). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17853893, PubMed:17556548, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:22660413}.;
- Pathway
- Endocytosis - Homo sapiens (human);Disease;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Infectious disease;EGFR1
(Consensus)
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- loftool
- 0.582
- rvis_EVS
- -0.31
- rvis_percentile_EVS
- 32.23
Haploinsufficiency Scores
- pHI
- 0.266
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.576
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.921
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Pdcd6ip
- Phenotype
- growth/size/body region phenotype; cellular phenotype; craniofacial 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); respiratory system phenotype; skeleton phenotype;
Gene ontology
- Biological process
- mitotic cytokinesis;actomyosin contractile ring assembly;apoptotic process;nucleus organization;mitotic metaphase plate congression;regulation of centrosome duplication;protein transport;viral life cycle;multivesicular body assembly;viral budding via host ESCRT complex;maintenance of epithelial cell apical/basal polarity;viral budding;protein homooligomerization;midbody abscission;bicellular tight junction assembly;regulation of membrane permeability;ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway;regulation of mitotic spindle assembly;positive regulation of exosomal secretion;regulation of extracellular exosome assembly;positive regulation of extracellular exosome assembly
- Cellular component
- immunological synapse;microtubule organizing center;cytosol;bicellular tight junction;focal adhesion;membrane;melanosome;actomyosin;extracellular exosome;endoplasmic reticulum exit site;Flemming body;extracellular vesicle
- Molecular function
- protein binding;proteinase activated receptor binding;protein homodimerization activity;calcium-dependent protein binding