SCG5

Chr 15

secretogranin V

Also known as: 7B2, P7B2, SGNE1, SgV

NCBI Gene: 6447 ENSG00000166922 UniProt: P05408 OMIM: 173120

This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Mechanism· predicted

📖

GeneReview available — SCG5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 1.02

OE 0.68 (0.40–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.61Z-score

OE missense 0.84 (0.71–0.99)

97 obs / 115.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.40–1.22)

0≤0.351.4

Missense OE?0.84 (0.71–0.99)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 11.8Missense obs/exp: 97 / 115.5Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in SCG5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

286 rare PASS variants

Rare truncating (LoF)

1 in 2,000

55 rare PASS variants

Rare synonymous (reference)

1 in 670

127 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCG5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 270	1 in 2,400
South Asian	~43k	1 in 180	1 in 630
Remaining (unassigned)	~30k	1 in 220	1 in 3,400
European (Finnish)	~27k	1 in 1,500	≈ 1 in 27,000
Admixed American	~22k	1 in 240	1 in 2,000
African / African American	~21k	1 in 240	1 in 2,100
East Asian	~20k	1 in 160	1 in 1,300
Ashkenazi Jewish	~13k	1 in 2,600	1 in 870
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓