SCHIP1

Chr 3

schwannomin interacting protein 1

Also known as: SCHIP-1

NCBI Gene: 29970 ENSG00000151967 UniProt: P0DPB3 OMIM: 619206

SCHIP1 enables identical protein binding activity and is predicted to be involved in positive regulation of hippo signaling and various developmental processes including face morphogenesis. Mutations cause autosomal dominant neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities. The gene is highly constrained against loss-of-function variants, consistent with its role in essential developmental pathways.

OMIM ResearchSummary from RefSeq

Enables identical protein binding activity. Predicted to be involved in positive regulation of hippo signaling. Predicted to act upstream of or within several processes, including face morphogenesis; fibroblast migration; and luteinization. Located in several cellular components, including cell junction; cytosol; and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.23

Clinical Summary— SCHIP1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 65 VUS of 68 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.987

Z-score 3.36

OE 0.00 (0.00–0.23)

Highly constrained

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

Missense Constraint?

1.90Z-score

OE missense 0.53 (0.43–0.65)

68 obs / 128.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.23)

0≤0.351.4

Missense OE?0.53 (0.43–0.65)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 0 / 13.2Missense obs/exp: 68 / 128.8Syn Z: 0.54

This gene — mechanism propensity

0.4983th %ile

GOF

0.5759th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.23

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS65

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	65	65
Likely Benign	0	1	1
Benign	0	0	0
Total	1	66	67

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap SCHIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →