SRP54

signal recognition particle 54, the group of Signal recognition particle

Basic information

Region (hg38): 14:34981957-35029686

Links

ENSG00000100883 ∙ NCBI:6729 ∙ OMIM:604857 ∙ HGNC:11301 ∙ Uniprot:P61011 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant severe congenital neutropenia (Supportive), mode of inheritance: AD
• Shwachman-Diamond syndrome (Supportive), mode of inheritance: AR
• neutropenia, severe congenital, 8, autosomal dominant (Strong), mode of inheritance: AD
• neutropenia, severe congenital, 8, autosomal dominant (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 8, autosomal dominant	AD	Allergy/Immunology/Infectious	Individuals have been described with recurrent infections, and awareness may allow prompt management and prophylactic measures; HSCT has been described	Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic	28972538; 29914977

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRP54 gene.

• not_provided (243 variants)
• Inborn_genetic_diseases (25 variants)
• Neutropenia,_severe_congenital,_8,_autosomal_dominant (10 variants)
• SRP54-related_disorder (7 variants)
• Shwachman-Diamond_syndrome_1 (4 variants)
• not_specified (3 variants)
• Ciliary_dyskinesia,_primary,_40 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRP54 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003136.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	47	5	54
missense	3	3	88	6		100
nonsense			2			2
start loss						0
frameshift			3			3
splice donor/acceptor (+/-2bp)						0
Total	3	3	95	53	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRP54	protein_coding	protein_coding	ENST00000556994	15	47611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00105	125738	0	5	125743	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.45	110	269	0.408	0.0000127	3400
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000621	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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).
• Pathway: Protein export - Homo sapiens (human);mRNA Processing;SRP-dependent cotranslational protein targeting to membrane;Translation;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.292

Intolerance Scores

• loftool: 0.108
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.839
• ghis: 0.661

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Srp54c

Zebrafish Information Network

• Gene name: srp54
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• 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
• Cellular component: nucleus;nucleolus;cytoplasm;signal recognition particle, endoplasmic reticulum targeting;cytosol;nuclear speck
• Molecular function: RNA binding;GTPase activity;protein binding;GTP binding;drug binding;7S RNA binding;GDP binding;endoplasmic reticulum signal peptide binding;ribonucleoprotein complex binding