ISL2

Chr 15

ISL LIM homeobox 2

NCBI Gene: 64843 ENSG00000159556 UniProt: Q96A47

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in axonogenesis; neuron fate specification; and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of neuron differentiation and neuron differentiation. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Research

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

0.67

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.111

Z-score 2.42

OE 0.29 (0.14–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.23Z-score

OE missense 0.75 (0.66–0.86)

150 obs / 198.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.14–0.67)

0≤0.351.4

Missense OE?0.75 (0.66–0.86)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 4 / 13.7Missense obs/exp: 150 / 198.8Syn Z: -1.20

Background carrier burden — how many people carry a rare variant somewhere in ISL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

506 rare PASS variants

Rare truncating (LoF)

1 in 6,500

45 rare PASS variants

Rare synonymous (reference)

1 in 170

247 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ISL2. 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 200	1 in 5,700
South Asian	~43k	1 in 130	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 130	1 in 3,400
European (Finnish)	~27k	1 in 680	≈ 1 in 6,800
Admixed American	~22k	1 in 110	≈ 1 in 22,000
African / African American	~21k	1 in 210	≈ 1 in 17,000
East Asian	~20k	1 in 170	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 980	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 310	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.