SLIRP

protein-coding

SRA stem-loop interacting RNA binding protein, the group of RNA binding motif containing

Gene summary

Steroid receptor RNA activator (SRA, or SRA1; MIM 603819) is a complex RNA molecule containing multiple stable stem-loop structures that functions in coactivation of nuclear receptors. SLIRP interacts with stem-loop structure-7 of SRA (STR7) and modulates nuclear receptor transactivation (Hatchell et al., 2006 [PubMed 16762838]).[supplied by OMIM, Mar 2008]

Previous symbols:

C14orf156

MANE transcript

NM_031210.6

Inheritance

ClinVar variants

U:21B:2

Top phenotype

Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

gnomAD constraint

pLI —, LoF o/e 1.36

Max pathogenic AF

—

Genomic locus

chr14:77,708,071-77,761,104

External References & Databases

Ensembl (ENSG00000119705)

Transcript & Mutation Effects

hg38 • Region Span ~53.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial encephalomyopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0004675

Submitter: G2P

inborn mitochondrial metabolism disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0004069

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLIRP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 19

Congenital lactic acidosis, Saguenay-Lac-Saint-Jean typeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031210.6. 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						0
missense			17 clinvar	2 clinvar		19
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	21	2	0	23

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031210.6	RefSeq	NP_112487.1	4	MANE Select
ENST00000557342.6	Ensembl	ENSP00000450909.1	4	MANE Select
NM_001267863.1	RefSeq	NP_001254792.1	4	Standard
NM_001267864.1	RefSeq	NP_001254793.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of mitochondrial RNA catabolic process
spermatid development
single fertilization
flagellated sperm motility
mitochondrion morphogenesis

Molecular Function

RNA binding
protein binding

Cellular Component

acrosomal vesicle
nucleus
mitochondrion
sperm flagellum
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000557342
Coding exons: 4
Length: 53034
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125746
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.570	73	60.5	1.21	0.00000290	708
Missense (PolyPhen)		19	18.589	1.0221		258
Synonymous	-1.30	30	22.2	1.35	0.00000113	208
Loss of Function	-0.801	8	5.90	1.36	2.50e-7	69

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: RNA-binding protein that acts as a nuclear receptor corepressor. Probably acts by binding the SRA RNA, and repressing the SRA-mediated nuclear receptor coactivation. Binds the STR7 loop of SRA RNA. Also able to repress glucocorticoid (GR), androgen (AR), thyroid (TR) and VDR-mediated transactivation. {ECO:0000269|PubMed:16762838}.;

Intolerance Scores

RVIS EVS: 0.04
RVIS percentile EVS: 56.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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