GIPC3
protein-codingGIPC PDZ domain containing family member 3, the group of PDZ domain containing
Gene summary
The protein encoded by this gene belongs to the GIPC family. Studies in mice suggest that this gene is required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion in the ear. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2011]
- C19orf64
- DFNB72
- DFNB15
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011160
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0019588
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011160
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011160
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0019497
Submitter: ClinGen
The GIPC3 gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 10/18/2016. This association was made using case-level data only. At least 9 variants (missense, nonsense, frameshift) have been reported in humans. GIPC3 was first associated with this disease in humans as early as 2011 (Charizopoulou et al.). Association is seen in at least 9 probands in 2 publications (21326233, 21660509). Variants in this gene segregated with disease in 36 additional family members. This gene-disease association is supported by a mouse model and rescue, and relevant functional evidence. In summary, GIPC3 is definitively associated with autosomal recessive nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 8/22/2017.
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 GIPC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133261.3. 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 | 3 | 45 | 48 | |||
| missense | 5 | 6 | 110 | 9 | 130 | |
| nonsense | 3 | 2 | 5 | |||
| start loss | 1 | 1 | ||||
| frameshift | 6 | 10 | 16 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 15 | 22 | 113 | 54 | 0 | 204 |
Highest pathogenic variant AF is 0.000061688595
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_573568.1 | 6 | MANE Select | |
| Ensembl | ENSP00000493901.2 | 6 | MANE Select | |
| RefSeq | NP_001398073.1 | 6 | Standard | |
| Ensembl | ENSP00000495068.1 | 6 | Standard |
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000322315
- Coding exons
- 6
- Length
- 7989
- Individuals with no LoFs
- 125663
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125690
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.177 | 173 | 180 | 0.963 | 0.0000117 | 2007 |
| Missense (PolyPhen) | 60 | 66.514 | 0.90207 | 673 | ||
| Synonymous | -0.0819 | 79 | 78.1 | 1.01 | 0.00000551 | 649 |
| Loss of Function | 1.73 | 5 | 11.3 | 0.444 | 5.72e-7 | 138 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion. {ECO:0000250}.;
- Disease
- DISEASE: Deafness, autosomal recessive, 15 (DFNB15) [MIM:601869]: A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:21326233, ECO:0000269|PubMed:21660509}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.310
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |