ISLR2

Chr 15

immunoglobulin superfamily containing leucine rich repeat 2

Also known as: LINX

NCBI Gene: 57611ENSG00000167178UniProt: Q6UXK2

Predicted to be involved in positive regulation of axon extension. Predicted to be located in plasma membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

127
ClinVar variants
35
Pathogenic / LP
0.11
pLI score
0
Active trials
Clinical Summary— ISLR2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 89 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.111
Z-score 2.84
OE 0.28 (0.14–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.23Z-score
OE missense 0.71 (0.65–0.78)
330 obs / 465.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.14–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 5 / 18.0Missense obs/exp: 330 / 465.7Syn Z: -0.38

ClinVar Variant Classifications

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic6
VUS89
Likely Benign3
29
Pathogenic
6
Likely Pathogenic
89
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
6
0
6
VUS
1
79
9
0
89
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total181441127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ISLR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of prospective aging drug targets via Mendelian randomization analysis.
Mao R et al.·Aging Cell
2024
Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid.
Kamalian A et al.·Fluids Barriers CNS
2024
Cerebrospinal Fluid Protein Biomarker Discovery in CLN3.
Dang Do AN et al.·J Proteome Res
2023
Potential therapeutic targets for sarcopenia identified by Mendelian randomisation.
Jiang W et al.·Age Ageing
2023
Transcriptomic Profiling Revealed Lnc-GOLGA6A-1 as a Novel Prognostic Biomarker of Meningioma Recurrence.
Slavik H et al.·Neurosurgery
2022
The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome.
Berner D et al.·Hum Mol Genet
2019
A novel ISLR2-linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension.
Alazami AM et al.·Hum Genet
2019
A 70‑RNA model based on SVR and RFE for predicting the pancreatic cancer clinical prognosis.
Chen X et al.·Methods
2022Functional
LOC283731 promoter hypermethylation prognosticates survival after radiochemotherapy in IDH1 wild-type glioblastoma patients.
Mock A et al.·Int J Cancer
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools