SRP72

signal recognition particle 72, the group of Signal recognition particle|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 4:56467617-56503681

Links

ENSG00000174780 ∙ NCBI:6731 ∙ OMIM:602122 ∙ HGNC:11303 ∙ Uniprot:O76094 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acute myeloid leukemia (Moderate), mode of inheritance: AD
• autosomal dominant aplasia and myelodysplasia (Limited), mode of inheritance: AD
• autosomal dominant aplasia and myelodysplasia (Supportive), mode of inheritance: AD
• autosomal dominant aplasia and myelodysplasia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bone marrow failure syndrome 1	AD	Audiologic/Otolaryngologic; Hematologic; Oncologic	Individuals have been described as having early-onset anemia/panyctopenia, as well as later myelodysplasia, and measures to detect and ameliorate hematologic findings may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Hematologic; Oncologic	22541560

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRP72 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRP72 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	78	7	90
missense			218	4	2	224
nonsense			6			6
start loss						0
frameshift			12			12
inframe indel			5			5
splice donor/acceptor (+/-2bp)			7			7
splice region			13	14	1	28
non coding			32	83	66	181
Total	0	0	285	165	75

Variants in SRP72

This is a list of pathogenic ClinVar variants found in the SRP72 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-56467626-C-T		Autosomal dominant aplasia and myelodysplasia • SRP72-related disorder	Uncertain significance (Aug 03, 2020)
4-56467637-T-C			Uncertain significance (Nov 07, 2023)
4-56467642-A-G		Autosomal dominant aplasia and myelodysplasia	Uncertain significance (Jan 12, 2018)
4-56467644-C-T		SRP72-related disorder	Likely benign (Jul 14, 2022)
4-56467652-G-C		not specified	Uncertain significance (Nov 20, 2024)
4-56467653-C-T		not specified	Likely benign (Dec 08, 2024)
4-56467653-C-CG		SRP72-related disorder	Uncertain significance (Dec 01, 2023)
4-56467654-G-A			Uncertain significance (Sep 27, 2022)
4-56467654-G-C		not specified • Autosomal dominant aplasia and myelodysplasia • SRP72-related disorder	Uncertain significance (Apr 23, 2024)
4-56467654-G-T		Autosomal dominant aplasia and myelodysplasia	Benign (Jan 26, 2024)
4-56467655-G-A		Autosomal dominant aplasia and myelodysplasia • not specified	Conflicting classifications of pathogenicity (Nov 17, 2024)
4-56467655-G-C		not specified • Autosomal dominant aplasia and myelodysplasia	Benign/Likely benign (Feb 01, 2024)
4-56467655-G-T		not specified • SRP72-related disorder	Uncertain significance (Nov 25, 2024)
4-56467656-G-A		not specified	Likely benign (Nov 18, 2024)
4-56467656-G-C		not specified	Likely benign (Nov 26, 2024)
4-56467656-G-T		Autosomal dominant aplasia and myelodysplasia	Benign (Feb 01, 2024)
4-56467657-G-A			Uncertain significance (Oct 01, 2022)
4-56467657-G-C			Uncertain significance (Dec 07, 2023)
4-56467658-G-A		Autosomal dominant aplasia and myelodysplasia • not specified	Conflicting classifications of pathogenicity (Oct 02, 2024)
4-56467658-G-C		not specified	Uncertain significance (Nov 22, 2024)
4-56467659-G-A			Likely benign (Dec 11, 2023)
4-56467659-G-C		not specified	Likely benign (Dec 06, 2024)
4-56467659-G-T			Likely benign (Nov 01, 2022)
4-56467659-GG-T			Uncertain significance (Nov 14, 2022)
4-56467660-G-A		SRP72-related disorder	Uncertain significance (Dec 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRP72	protein_coding	protein_coding	ENST00000342756	19	36759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00171	0.998	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	294	347	0.846	0.0000174	4381
Missense in Polyphen		65	93.623	0.69427		1285
Synonymous	0.948	108	121	0.890	0.00000582	1232
Loss of Function	4.13	13	41.8	0.311	0.00000211	512

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000519	0.000518
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000173	0.000163
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000134	0.000132
Middle Eastern	0.000173	0.000163
South Asian	0.0000655	0.0000653
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Signal-recognition-particle assembly has a crucial role in targeting secretory proteins to the rough endoplasmic reticulum membrane. Binds the 7S RNA only in presence of SRP68. This ribonucleoprotein complex might interact directly with the docking protein in the ER membrane and possibly participate in the elongation arrest function.
• Disease: DISEASE: Bone marrow failure syndrome 1 (BMFS1) [MIM:614675]: An autosomal dominant disease characterized by aplastic anemia and myelodysplasia resulting from bone marrow failure. Aplastic anemia is a form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. Myelodysplasia is a clonal hematopoietic stem cell disorder in which immature cells in the bone marrow become malformed and dysfunctional. {ECO:0000269|PubMed:22541560}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein export - Homo sapiens (human);SRP-dependent cotranslational protein targeting to membrane;Translation;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.482
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.739
• hipred: Y
• hipred_score: 0.602
• ghis: 0.680

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Srp72

Gene ontology

• Biological process: SRP-dependent cotranslational protein targeting to membrane;SRP-dependent cotranslational protein targeting to membrane, translocation;response to drug
• Cellular component: endoplasmic reticulum;signal recognition particle, endoplasmic reticulum targeting;cytosol;signal recognition particle
• Molecular function: RNA binding;signal recognition particle binding;protein binding;7S RNA binding;TPR domain binding;ribosome binding