SLITRK1

Chr 13

SLIT and NTRK like family member 1

Also known as: LRRC12, TTM

NCBI Gene: 114798 ENSG00000178235 UniProt: Q96PX8

SLITRK1 encodes an integral membrane protein with leucine-rich repeat domains that promotes excitatory synapse differentiation and enhances neuronal dendrite outgrowth. Mutations cause Tourette syndrome and possibly trichotillomania, with autosomal dominant and multifactorial inheritance patterns. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.34), indicating that complete protein loss is likely not tolerated.

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. However, the protein encoded by this gene lacks the region of homology to neurotrophin receptors. This protein is thought to be involved in neurite outgrowth. Mutations in this gene may be associated with Tourette syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTrichotillomania

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.957

Z-score 3.58

OE 0.11 (0.04–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.41Z-score

OE missense 0.94 (0.86–1.03)

329 obs / 350.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.34)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 2 / 18.7Missense obs/exp: 329 / 350.3Syn Z: -1.77

Background carrier burden — how many people carry a rare variant somewhere in SLITRK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

836 rare PASS variants

Rare truncating (LoF)

1 in 9,900

26 rare PASS variants

Rare synonymous (reference)

1 in 180

417 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLITRK1. 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 180	1 in 14,000
South Asian	~43k	1 in 89	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 78	none seen
European (Finnish)	~27k	1 in 510	≈ 1 in 27,000
Admixed American	~22k	1 in 77	≈ 1 in 7,500
African / African American	~21k	1 in 92	≈ 1 in 10,000
East Asian	~20k	1 in 100	1 in 2,600
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 180	none seen

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 ↓