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.

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Deafness and myopiaMIM #221200

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · high myopia-sensorineural deafness syndrome · AR · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.27

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in SLITRK6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

1,070 rare PASS variants

Rare truncating (LoF)

1 in 2,000

110 rare PASS variants

Rare synonymous (reference)

1 in 130

421 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLITRK6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 86	1 in 2,100
South Asian	~43k	1 in 45	1 in 1,700
Remaining (unassigned)	~30k	1 in 58	1 in 4,300
European (Finnish)	~27k	1 in 230	≈ 1 in 27,000
Admixed American	~22k	1 in 54	1 in 1,200
African / African American	~21k	1 in 43	1 in 1,500
East Asian	~20k	1 in 55	1 in 2,800
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 13,000
Middle Eastern	~2,882	1 in 54	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓