PJVK
protein-codingpejvakin, the group of Gasdermins
Gene summary
The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59). [provided by RefSeq, Dec 2008]
- DFNB59
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012445
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0019497
Submitter: ClinGen
The relationship between DFNB59 (aka PJVK) and autosomal recessive nonsyndromic genetic deafness was evaluated using the ClinGen Clinical Validity Framework as of 11/17/2017. Variants in PJVK were first reported in humans with this disease as early as 2006 (Delmaghani et al., PMID 16804542). At least 8 unique variants (missense, in-frame indel, nonsense, frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, animal models, and expression studies that help elucidate the role of PJVK in the peroxisomes of inner ear hair cells and neurons (PMIDs: 16804542, 26166082, 22617256, 28964305, 17373699, 25631766). Variants in this gene have been reported in at least 8 probands in 14 publications. Variants in this gene segregated with disease in more than 33 additional family members.More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is hypothesized to be that the PJVK gene is critical to the "regulation of peroxisomal dynamics and the antioxidant defense triggered by noise exposure in hair cells and auditory neurons of the inner ear"(PMID: 26544930). In summary, DFNB59 is definitively associated with ARNSHL. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 12/19/2017.
Inheritance Pattern: AR
Disease ID:MONDO:0012445
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012445
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0019588
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PJVK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001042702.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 73 | 78 | ||
| missense | 3 | 3 | 77 | 7 | 90 | |
| nonsense | 7 | 6 | 1 | 14 | ||
| start loss | 1 | 1 | ||||
| frameshift | 17 | 8 | 25 | |||
| splice donor/acceptor (+/-2bp) | 2 | 3 | 5 | |||
| Total | 29 | 21 | 83 | 80 | 0 | 213 |
Highest pathogenic variant AF is 0.00009975427
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001036167.1 | 6 | MANE Select | |
| Ensembl | ENSP00000495855.2 | 6 | MANE Select | |
| RefSeq | NP_001340704.1 | 7 | Standard | |
| RefSeq | NP_001340705.1 | 6 | Standard |
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409117
- Coding exons
- 6
- Length
- 9955
- Individuals with no LoFs
- 124818
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 60
- Defined
- 124878
- p
- 0.000240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.134 | 181 | 186 | 0.972 | 0.00000919 | 2286 |
| Missense (PolyPhen) | 58 | 59.773 | 0.97034 | 775 | ||
| Synonymous | 0.774 | 57 | 64.9 | 0.878 | 0.00000309 | 686 |
| Loss of Function | 1.07 | 14 | 19.1 | 0.735 | 0.00000140 | 204 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00045 | 0.00045 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00039 | 0.00039 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00029 | 0.00026 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential in the activity of auditory pathway neurons.;
Intolerance Scores
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (gene trap)
- N