SLITRK3

Chr 3

SLIT and NTRK like family member 3

NCBI Gene: 22865 ENSG00000121871 UniProt: O94933 OMIM: 609679

This gene encodes a member of the Slitrk family of structurally related transmembrane proteins that are involved in controlling neurite outgrowth. The encoded protein contains two leucine-rich repeat (LRR) domains and a C-terminal domain that is partially similar to Trk neurotrophin receptor protein. Enhanced expression of this gene was found in tissue from several different types of tumors. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Jan 2016]

OMIM Research

OMIM 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

0.34

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.939

Z-score 4.32

OE 0.16 (0.08–0.34)

Highly constrained

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

Missense Constraint?

0.59Z-score

OE missense 0.93 (0.86–1.00)

489 obs / 527.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.34)

0≤0.351.4

Missense OE?0.93 (0.86–1.00)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 5 / 30.9Missense obs/exp: 489 / 527.1Syn Z: -1.84

Background carrier burden — how many people carry a rare variant somewhere in SLITRK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

1,194 rare PASS variants

Rare truncating (LoF)

1 in 3,000

40 rare PASS variants

Rare synonymous (reference)

1 in 120

588 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLITRK3. 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 100	1 in 2,700
South Asian	~43k	1 in 74	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 78	≈ 1 in 7,400
European (Finnish)	~27k	1 in 130	none seen
Admixed American	~22k	1 in 71	1 in 1,100
African / African American	~21k	1 in 55	≈ 1 in 10,000
East Asian	~20k	1 in 64	≈ 1 in 9,800
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 97	≈ 1 in 1,400

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 ↓