SRP68

protein-coding

signal recognition particle 68, the group of Signal recognition particle

Gene summary

This gene encodes a subunit of the signal recognition particle (SRP). The SRP is a ribonucleoprotein complex that transports secreted and membrane proteins to the endoplasmic reticulum for processing. The complex includes a 7S RNA and six protein subunits. The encoded protein is the 68kDa component of the SRP, and forms a heterodimer with the 72kDa subunit that is required for SRP function. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and three pseudogenes of this gene are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, May 2012]

MANE transcript

NM_014230.4

Inheritance

ClinVar variants

P:1U:85B:4

Top phenotype

Neutropenia, severe congenital, 10, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr17:76,038,775-76,072,517

External References & Databases

Ensembl (ENSG00000167881)

Transcript & Mutation Effects

hg38 • Region Span ~33.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neutropenia, severe congenital, 10, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957809

Submitter: Ambry Genetics

neutropenia, severe congenital, 10, autosomal recessiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957809

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neutropenia, severe congenital, 10, autosomal recessiveAR

Manifestation: Allergy/Immunology/Infectious; Hematologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described with recurrent infections, and awareness may allow prompt management (eg, with GCSF) and prophylactic measures

Refs: 32273475

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRP68 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 74

SRP68-related conditionTotal: 2

not providedTotal: 1

Neutropenia, severe congenital, 10, autosomal recessiveTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014230.4. 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			5 clinvar	3 clinvar		8
missense			73 clinvar	1 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		7 clinvar			8
Total	1	0	85	4	0	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014230.4	RefSeq	NP_055045.2	16	MANE Select
ENST00000307877.7	Ensembl	ENSP00000312066.1	16	MANE Select
NM_001260502.2	RefSeq	NP_001247431.1	15	Standard
NM_001260503.2	RefSeq	NP_001247432.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
srp68	Danio rerio	Structure: cartilage element Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

srp68

Danio rerio

Structure: cartilage element

Quality: morphology

abnormal

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
response to drug

Molecular Function

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

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307877
Coding exons: 16
Length: 33551
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.03	255	364	0.701	0.0000205	4084
Missense (PolyPhen)		84	136.46	0.61558		1448
Synonymous	0.770	125	136	0.916	0.00000724	1197
Loss of Function	4.16	10	37.5	0.267	0.00000189	445

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.000054	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

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. SRP68 binds the 7S RNA, SRP72 binds to this complex subsequently. This ribonucleoprotein complex might interact directly with the docking protein in the ER membrane and possibly participate in the elongation arrest function.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.142
RVIS EVS: 0.51
RVIS percentile EVS: 80.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.536

Gene Damage Prediction

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