SLITRK2

Chr XX-linked

SLIT and NTRK like family member 2

Also known as: CXorf1, CXorf2, SLITL1, TMEM257, XLID111

NCBI Gene: 84631 ENSG00000185985 UniProt: Q9H156 OMIM: 300561

This gene encodes an integral membrane protein that promotes excitatory synapse differentiation and suppresses neurite outgrowth through negative regulation of NTRK2. Mutations cause X-linked intellectual developmental disorder. The gene follows X-linked inheritance and shows moderate constraint against loss-of-function variants (LOEUF 0.69).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an integral membrane protein that contains two N-terminal leucine-rich repeats domains and contains C-terminal regions similar to neurotrophin receptors. The encoded protein may play a role in modulating neurite activity. Alternatively spliced transcript variants encoding the same protein have been described.[provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 111MIM #301107

X-linked

Clinical highlights

Gene–disease validity (ClinGen)

Limited · X-linked complex neurodevelopmental disorder · XL · ClinGen 2025

not for standalone diagnostic reporting

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.006

Z-score 2.54

OE 0.37 (0.21–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.20Z-score

OE missense 0.66 (0.59–0.73)

212 obs / 323.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.37 (0.21–0.69)

0≤0.351.4

Missense OE?0.66 (0.59–0.73)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 7 / 18.9Missense obs/exp: 212 / 323.0Syn Z: -0.73

Background carrier burden — how many people carry a rare variant somewhere in SLITRK2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

525 rare PASS variants

Rare truncating (LoF)

1 in 22,000

20 rare PASS variants

Rare synonymous (reference)

1 in 160

323 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLITRK2. 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)	~561k	1 in 140	1 in 31,000
South Asian	~36k	1 in 170	none seen
Remaining (unassigned)	~31k	1 in 100	none seen
European (Finnish)	~27k	1 in 710	1 in 3,500
Admixed American	~23k	1 in 170	≈ 1 in 12,000
African / African American	~21k	1 in 250	≈ 1 in 18,000
East Asian	~20k	1 in 160	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 610	none seen
Middle Eastern	~2,758	1 in 160	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 ↓