SRPRB

Chr 3

SRP receptor subunit beta

Also known as: APMCF1, SR-beta

NCBI Gene: 58477 ENSG00000144867 UniProt: Q9Y5M8 OMIM: 616883

The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.83

Clinical Summary— SRPRB

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 53 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.006

Z-score 2.04

OE 0.42 (0.23–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.87–1.15)

146 obs / 145.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.42 (0.23–0.83)

0≤0.351.4

Missense OE?1.00 (0.87–1.15)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 6 / 14.3Missense obs/exp: 146 / 145.8Syn Z: -0.01

This gene — mechanism propensity

0.6743th %ile

GOF

0.4874th %ile

LOF

0.3163th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Benign1

Conflicting1

VUS

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	39	0	0	39
Likely Benign	0	0	0	0	0
Benign	0	0	0	1	1
Conflicting	—				1
Total	0	39	0	1	41

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap SRPRB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →