IQCJ-SCHIP1

Chr 3

IQCJ-SCHIP1 readthrough

NCBI Gene: 100505385 ENSG00000283154 UniProt: B3KU38 OMIM: 611622

The IQCJ-SCHIP1 fusion protein organizes molecular complexes at nodes of Ranvier and axon initial segments, facilitating action potential conduction in myelinated neurons and supporting axon outgrowth and guidance. This gene is highly constrained against loss-of-function variants (LOEUF 0.529), but no human disease phenotypes have been definitively associated with mutations in this locus to date.

OMIM ResearchSummary from RefSeq, UniProt

This locus represents naturally occurring read-through transcription from the neighboring IQ motif containing J (IQCJ) and schwannomin interacting protein 1 (SCHIP1) genes. Alternative splicing results in multiple transcript variants that are composed of in-frame exons from each individual gene. The resulting fusion products are thought to be components of the multimolecular complexes of axon initial segments and nodes of Ranvier, and they may play a role in calcium-mediated responses. [provided by RefSeq, Oct 2010]

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

0.53

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.027

Z-score 3.42

OE 0.29 (0.17–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.69Z-score

OE missense 0.89 (0.80–0.98)

254 obs / 287.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.17–0.53)

0≤0.351.4

Missense OE?0.89 (0.80–0.98)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 8 / 27.3Missense obs/exp: 254 / 287.0Syn Z: 0.02

Background carrier burden — how many people carry a rare variant somewhere in IQCJ-SCHIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

827 rare PASS variants

Rare truncating (LoF)

1 in 1,400

105 rare PASS variants

Rare synonymous (reference)

1 in 150

269 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IQCJ-SCHIP1. 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 160	1 in 1,300
South Asian	~43k	1 in 63	1 in 670
Remaining (unassigned)	~30k	1 in 110	1 in 2,300
European (Finnish)	~27k	1 in 290	1 in 4,300
Admixed American	~22k	1 in 59	1 in 1,800
African / African American	~21k	1 in 78	1 in 1,300
East Asian	~20k	1 in 96	1 in 940
Ashkenazi Jewish	~13k	1 in 260	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	≈ 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.