SLITRK6
protein-codingSLIT and NTRK like family member 6, the group of SLIT and NTRK like family
Gene summary
This gene encodes a member of the SLITRK protein family. Members of this family are integral membrane proteins that are characterized by two N-terminal leucine-rich repeat (LRR) domains and a C-terminal region that shares homology with trk neurotrophin receptors. This protein functions as a regulator of neurite outgrowth required for normal hearing and vision. Mutations in this gene are a cause of myopia and deafness. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0019588
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: ClinGen
SLITRK6 gene was reported in relation to autosomal recessive deafness and myopia in 2013 (Tekin et al.). At least 5 unique variants (nonsense, frameshift, in-frame indel etc.) have been reported in humans. This gene-disease association is supported by a mouse model and expression studies (Tekin et al. 2013 and Katayama et al. 2009) as well as case-level and segregation data. In summary, SLITRK6 is definitively associated with autosomal recessive deafness and myopia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time
Inheritance Pattern: AR
Disease ID:MONDO:0009082
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Ophthalmologic
Intervention: Audiologic/Otolaryngologic
Rationale: Awareness of prelingual hearing loss may allow early interventions related to speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLITRK6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032229.3. 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 | 1 | 62 | 4 | 67 | ||
| missense | 209 | 12 | 2 | 223 | ||
| nonsense | 2 | 6 | 1 | 9 | ||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | 2 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 7 | 213 | 74 | 6 | 304 |
Highest pathogenic variant AF is 0.000029767147
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115605.2 | 1 | MANE Select | |
| Ensembl | ENSP00000495507.1 | 1 | MANE Select | |
| Ensembl | ENSP00000496428.1 | 1 | Standard | |
| Ensembl | ENSP00000496428.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- EGFR1
- Receptor-type tyrosine-protein phosphatases
- Protein-protein interactions at synapses
Biological Process
- startle response
- lens development in camera-type eye
- auditory receptor cell morphogenesis
- axonogenesis
- synapse assembly
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400286
- Coding exons
- 1
- Length
- 6699
- Individuals with no LoFs
- 124682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 69
- Defined
- 124751
- p
- 0.000277
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.381 | 456 | 434 | 1.05 | 0.0000213 | 5526 |
| Missense (PolyPhen) | 145 | 144.94 | 1.0004 | 1985 | ||
| Synonymous | -2.07 | 198 | 164 | 1.21 | 0.00000835 | 1648 |
| Loss of Function | 0.511 | 22 | 24.7 | 0.889 | 0.00000142 | 347 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00030 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulator of neurite outgrowth required for normal hearing and vision. {ECO:0000269|PubMed:23543054}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.820
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 13.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.158
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |