SLITRK6

Chr 13AR

SLIT and NTRK like family member 6

Also known as: DFNMYP

NCBI Gene: 84189 ENSG00000184564 UniProt: Q9H5Y7 OMIM: 609681

This protein regulates neurite outgrowth and is required for normal hearing and vision. Mutations cause autosomal recessive deafness and myopia, affecting both auditory and visual systems. The gene shows strong constraint against loss-of-function variants (pLI near 1), indicating intolerance to complete protein loss.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.271 OMIM phenotype

Clinical Summary— SLITRK6

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Gene-Disease Validity (ClinGen)

high myopia-sensorineural deafness syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 202 VUS of 304 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLITRK6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.38Z-score

OE missense 1.05 (0.97–1.14)

456 obs / 433.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.89 (0.63–1.27)

0≤0.351.4

Missense OE?1.05 (0.97–1.14)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 22 / 24.7Missense obs/exp: 456 / 433.7Syn Z: -2.07

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLITRK6-related deafness and myopiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6453th %ile

GOF

0.7127th %ile

LOF

0.4135th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

304 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic5

VUS202

Likely Benign71

Benign16

Conflicting4

Pathogenic

Likely Pathogenic

202

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	5	0	0	0	5
VUS	3	198	0	1	202
Likely Benign	0	9	3	59	71
Benign	0	2	7	7	16
Conflicting	—				4
Total	11	210	10	67	302

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

View in ClinVar →

81 pathogenic / likely-pathogenic (of 90) ClinVar copy-number / structural variants overlap SLITRK6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →