SCIMP

Chr 17

SLP adaptor and CSK interacting membrane protein

Also known as: C17orf87, UNQ5783

NCBI Gene: 388325 ENSG00000161929 UniProt: Q6UWF3 OMIM: 614406

The protein encoded by this gene functions as a transmembrane adaptor that scaffolds signaling proteins in immune cells, facilitating MHC class II signal transduction, toll-like receptor signaling, and immune synapse formation in antigen-presenting cells. Mutations in SCIMP cause autosomal recessive immunodeficiency with recurrent infections. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a transmembrane adaptor protein that is expressed in antigen-presenting cells and is localized in the immunologic synapse. The encoded protein is involved in major histocompatibility complex class II signal transduction and immune synapse formation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.41

Clinical Summary— SCIMP

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.41LOEUF

pLI 0.000

Z-score 0.75

OE 0.72 (0.39–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.46Z-score

OE missense 0.85 (0.70–1.05)

66 obs / 77.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.39–1.41)

0≤0.351.4

Missense OE?0.85 (0.70–1.05)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 6 / 8.4Missense obs/exp: 66 / 77.4Syn Z: 0.65

This gene — mechanism propensity

0.76top 25%

GOF

0.85top 5%

LOF

0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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.