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…

DNmechanismLOEUF 0.53

Clinical Summary— IQCJ-SCHIP1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 88 VUS of 91 total submissions

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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

This gene — mechanism propensity

0.6841th %ile

GOF

0.6346th %ile

LOF

0.4038th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS88

Likely Benign1

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	0	88	88
Likely Benign	0	1	1
Benign	0	0	0
Total	1	89	90

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap IQCJ-SCHIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →