SRPRA

Chr 11

SRP receptor subunit alpha

Also known as: DP, SRPR, Sralpha

The protein is a subunit of the endoplasmic reticulum signal recognition particle receptor that ensures correct targeting of nascent secretory and membrane proteins to the ER membrane system through GTP-dependent interactions with SRP54. Mutations cause autosomal recessive intellectual developmental disorder with seizures, hypotonia, and brain abnormalities, with onset typically in infancy or early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.39), indicating that complete loss of function is poorly tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
67
P/LP submissions
1%
P/LP missense
0.39
LOEUF
Mechanism
Clinical SummarySRPRA
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
67 unique Pathogenic / Likely Pathogenic· 51 VUS of 156 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.778
Z-score 3.92
OE 0.19 (0.100.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.17Z-score
OE missense 0.83 (0.760.92)
329 obs / 394.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.100.39)
00.351.4
Missense OE0.83 (0.760.92)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 27.0Missense obs/exp: 329 / 394.1Syn Z: -0.68

ClinVar Variant Classifications

156 submitted variants in ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic2
VUS51
Likely Benign6
Benign2
65
Pathogenic
2
Likely Pathogenic
51
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
64
0
65
Likely Pathogenic
0
0
2
0
2
VUS
1
43
7
0
51
Likely Benign
0
0
1
5
6
Benign
0
1
1
0
2
Total145755126

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SRPRA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC