SRA1

protein-coding

steroid receptor RNA activator 1

Gene summary

Both long non-coding and protein-coding RNAs are transcribed from this gene, and they represent alternatively spliced transcript variants. This gene was initially defined as a non-coding RNA, which is a coactivator for several nuclear receptors (NRs) and is associated with breast cancer. It has now been found that this gene is involved in the regulation of many NR and non-NR activities, including metabolism, adipogenesis and chromatin organization. The long non-coding RNA transcripts interact with a variety of proteins, including the protein encoded by this gene. The encoded protein acts as a transcriptional repressor by binding to the non-coding RNA. [provided by RefSeq, Mar 2012]

MANE transcript

NM_001035235.4

Inheritance

—

ClinVar variants

U:60B:23

Top phenotype

SRA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr5:140,537,340-140,557,677

External References & Databases

Ensembl (ENSG00000213523)

Transcript & Mutation Effects

hg38 • Region Span ~20.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SRA1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 45

SRA1-related disorderTotal: 10

AmenorrheaTotal: 1

Hypogonadism with anosmiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001035235.4. 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				7 clinvar	4 clinvar	11
missense			55 clinvar	8 clinvar	4 clinvar	67
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	60	15	8	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001035235.4	RefSeq	NP_001030312.3	5	MANE Select
ENST00000336283.9	Ensembl	ENSP00000337513.6	5	MANE Select
NM_001253764.2	RefSeq	NP_001240693.1	3	Standard
ENST00000602657.1	Ensembl	ENSP00000473378.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sra1	Danio rerio	Structure: pericardium Quality: edematous abnormal

Gene / Model

Organism

Observed Phenotype

sra1

Danio rerio

Structure: pericardium

Quality: edematous

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mechanism of gene regulation by peroxisome proliferators via ppara
Validated nuclear estrogen receptor alpha network

Biological Process

regulation of transcription by RNA polymerase II
apoptotic process
cell population proliferation
cell differentiation
regulation of apoptotic process

Molecular Function

steroid receptor RNA activator RNA binding
transcription coactivator activity
protein binding
nuclear receptor transcription coactivator activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000336283
Coding exons: 5
Length: 20971
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.331	142	131	1.08	0.00000679	1472
Missense (PolyPhen)		59	51.524	1.1451		621
Synonymous	-0.208	52	50.1	1.04	0.00000245	479
Loss of Function	0.535	9	10.9	0.825	5.50e-7	120

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand- dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis. {ECO:0000269|PubMed:10199399, ECO:0000269|PubMed:12943696, ECO:0000269|PubMed:14517287, ECO:0000269|PubMed:15147866, ECO:0000269|PubMed:15351741}.;

Recessive Scores

pRec: 0.0882

Intolerance Scores

LoFtool: 0.966
RVIS EVS: 0.6
RVIS percentile EVS: 82.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High