SRP72

protein-coding

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

Gene summary

This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_006947.4

Inheritance

ClinVar variants

U:825B:314

Top phenotype

Bone marrow failure syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr4:56,467,617-56,503,681

External References & Databases

Ensembl (ENSG00000174780)

Transcript & Mutation Effects

hg38 • Region Span ~36.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant aplasia and myelodysplasiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013851

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant aplasia and myelodysplasiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013851

Submitter: PanelApp Australia

autosomal dominant aplasia and myelodysplasiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013851

Submitter: Ambry Genetics

autosomal dominant aplasia and myelodysplasiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013851

Submitter: Orphanet

acute myeloid leukemiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0018874

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Bone marrow failure syndrome 1AD

Manifestation: Audiologic/Otolaryngologic; Hematologic; Oncologic

Intervention: Audiologic/Otolaryngologic; Hematologic; Oncologic

Rationale: 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

Refs: 22541560

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRP72 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 965

not providedTotal: 657

SRP72-related disorderTotal: 57

Autosomal dominant aplasia and myelodysplasiaTotal: 54

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006947.4. 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			8 clinvar	296 clinvar		304
missense			760 clinvar	14 clinvar	4 clinvar	778
nonsense			13 clinvar			13
start loss			1 clinvar			1
frameshift			22 clinvar			22
splice donor/acceptor (+/-2bp)			21 clinvar			21
Total	0	0	825	310	4	1139

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006947.4	RefSeq	NP_008878.3	19	MANE Select
ENST00000642900.1	Ensembl	ENSP00000495128.1	19	MANE Select
NM_001267722.2	RefSeq	NP_001254651.1	17	Standard
ENST00000504757.2	Ensembl	ENSP00000473576.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)
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
response to drug

Molecular Function

RNA binding
signal recognition particle binding
protein binding
7S RNA binding
TPR domain binding

Cellular Component

endoplasmic reticulum
signal recognition particle, endoplasmic reticulum targeting
cytosol
signal recognition particle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342756
Coding exons: 19
Length: 36759
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	294	347	0.846	0.0000174	4381
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.482
RVIS EVS: -0.6
RVIS percentile EVS: 18.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.896

Gene Damage Prediction

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