SLITRK6

Chr 13AR

SLIT and NTRK like family member 6

Also known as: DFNMYP

NCBI Gene: 84189ENSG00000184564UniProt: Q9H5Y7

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]

Primary Disease Associations & Inheritance

Deafness and myopiaMIM #221200
AR
388
ClinVar variants
89
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLITRK6
🧬
Gene-Disease Validity (ClinGen)
high myopia-sensorineural deafness syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
89 Pathogenic / Likely Pathogenic· 208 VUS of 388 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.27LOEUF
pLI 0.000
Z-score 0.51
OE 0.89 (0.63–1.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.38Z-score
OE missense 1.05 (0.97–1.14)
456 obs / 433.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.89 (0.63–1.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.97–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 22 / 24.7Missense obs/exp: 456 / 433.7Syn Z: -2.07

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic6
VUS208
Likely Benign71
Benign16
Conflicting4
83
Pathogenic
6
Likely Pathogenic
208
VUS
71
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
81
0
83
Likely Pathogenic
0
0
6
0
6
VUS
3
195
9
1
208
Likely Benign
0
9
3
59
71
Benign
0
2
7
7
16
Conflicting
—4
Total420710667388

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLITRK6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLITRK6-related deafness and myopia

definitive
ARLoss Of FunctionAbsent Gene Product
EyeEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness and myopia

MIM #221200

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLITRK6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLITRK6 mutations cause myopia and deafness in humans and mice.
Tekin M et al.·J Clin Invest
2013
SLITRK6 promotes the progression of lung adenocarcinoma by regulating PI3K/AKT/mTOR signaling and Warburg effect.
Yu F et al.·Apoptosis
2023
A homozygous SLITRK6 nonsense mutation is associated with progressive auditory neuropathy in humans.
Morlet T et al.·Laryngoscope
2014
Systems biology approach uncovers candidates for kidney-heart interorgan crosstalk after myocardial infarction.
Wolf H et al.·Sci Rep
2025
Efficacy and toxicity of antibody-drug conjugates in the treatment of metastatic urothelial cancer: A scoping review.
Padua TC et al.·Urol Oncol
2022Review
Development of ASG-15ME, a Novel Antibody-Drug Conjugate Targeting SLITRK6, a New Urothelial Cancer Biomarker.
Morrison K et al.·Mol Cancer Ther
2016
Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families.
Doll J et al.·Genes (Basel)
2020
Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison.
Sanford T et al.·PLoS One
2015
Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
Greenwood TA et al.·PLoS One
2013
Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT).
Jia Y et al.·Int J Clin Exp Pathol
2014Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools