SLITRK5

Chr 13

SLIT and NTRK like family member 5

Also known as: LRRC11, bA364G4.2

NCBI Gene: 26050 ENSG00000165300 UniProt: O94991

SLITRK5 encodes an integral membrane protein that suppresses neurite outgrowth and is expressed predominantly in neural tissues. Mutations cause Tourette syndrome and obsessive-compulsive disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.87), indicating that complete loss of function is likely not tolerated.

ResearchSummary from RefSeq, UniProt

Members of the SLITRK family, such as SLITRK5, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, including SLITRK5, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003 [PubMed 14557068]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

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

0.38

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.870

Z-score 3.81

OE 0.16 (0.08–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.93–1.07)

546 obs / 549.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.38)

0≤0.351.4

Missense OE?0.99 (0.93–1.07)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 4 / 24.3Missense obs/exp: 546 / 549.5Syn Z: -3.08

Background carrier burden — how many people carry a rare variant somewhere in SLITRK5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,383 rare PASS variants

Rare truncating (LoF)

1 in 6,500

65 rare PASS variants

Rare synonymous (reference)

1 in 84

688 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLITRK5. 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 59	1 in 9,400
South Asian	~43k	1 in 49	1 in 2,700
Remaining (unassigned)	~30k	1 in 44	≈ 1 in 7,500
European (Finnish)	~27k	1 in 210	≈ 1 in 13,000
Admixed American	~22k	1 in 53	≈ 1 in 5,600
African / African American	~21k	1 in 58	1 in 2,900
East Asian	~20k	1 in 47	1 in 2,000
Ashkenazi Jewish	~13k	1 in 150	none seen
Middle Eastern	~2,884	1 in 61	≈ 1 in 2,900

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 ↓