SRP54
protein-codingsignal recognition particle 54, the group of Signal recognition particle
Gene summary
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 cytoplasm and nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. Implicated in severe congenital neutropenia 8. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0032899
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0032899
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032899
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic
Intervention: Allergy/Immunology/Infectious
Rationale: Individuals have been described with recurrent infections, and awareness may allow prompt management and prophylactic measures; HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SRP54 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003136.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 68 | 2 | 73 | ||
| missense | 3 | 3 | 121 | 6 | 133 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 3 | 3 | 131 | 74 | 2 | 213 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003127.1 | 15 | MANE Select | |
| Ensembl | ENSP00000216774.6 | 15 | MANE Select | |
| RefSeq | NP_001139754.1 | 14 | Standard | |
| RefSeq | NP_001397946.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| srp54 | Danio rerio | Structure: neutrophil Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein export - Homo sapiens (human)
- mRNA Processing
- SRP-dependent cotranslational protein targeting to membrane
- Translation
- Metabolism of proteins
Biological Process
- SRP-dependent cotranslational protein targeting to membrane
- SRP-dependent cotranslational protein targeting to membrane, translocation
- SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
- response to drug
- protein targeting to ER
Molecular Function
- RNA binding
- GTPase activity
- protein binding
- GTP binding
- drug binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
- signal recognition particle, endoplasmic reticulum targeting
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000556994
- Coding exons
- 15
- Length
- 47611
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125743
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.45 | 110 | 269 | 0.408 | 0.0000127 | 3400 |
| Missense (PolyPhen) | 19 | 89.247 | 0.21289 | 1106 | ||
| Synonymous | 0.0846 | 84 | 85.0 | 0.988 | 0.00000444 | 860 |
| Loss of Function | 4.62 | 2 | 28.7 | 0.0697 | 0.00000140 | 359 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to the signal sequence of presecretory protein when they emerge from the ribosomes and transfers them to TRAM (translocating chain-associating membrane protein).;
Recessive Scores
- pRec
- 0.292
Intolerance Scores
- LoFtool
- 0.108
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |