SRP54

Chr 14AD

signal recognition particle 54

Also known as: SCN8

NCBI Gene: 6729ENSG00000100883UniProt: P61011OMIM: 604857

Enables several functions, including 7S RNA binding activity; endoplasmic reticulum signal peptide binding activity; and guanyl ribonucleotide binding activity. Contributes to GTPase activity. Involved in granulocyte differentiation and protein targeting to ER. Located in cytosol and nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. Implicated in severe congenital neutropenia 8. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neutropenia, severe congenital, 8, autosomal dominantMIM #618752
AD

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
11
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.22
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.22LOEUF
pLI 0.999
Z-score 4.62
OE 0.07 (0.03–0.22)
Highly constrained

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

Missense Constraint?
3.45Z-score
OE missense 0.41 (0.35–0.48)
110 obs / 269.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.07 (0.03–0.22)
0≤0.351.4
Missense OE?0.41 (0.35–0.48)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 2 / 28.7Missense obs/exp: 110 / 269.5Syn Z: 0.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SRP54 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients