SCG2

Chr 2

secretogranin II

Also known as: CHGC, EM66, SN, SgII

Secretogranin II functions in the packaging and sorting of peptide hormones and neuropeptides into secretory vesicles in neuroendocrine cells, and is cleaved to produce the active peptide secretoneurin. Mutations in SCG2 cause autosomal recessive familial tumoral calcinosis, a disorder characterized by abnormal calcium and phosphate metabolism leading to ectopic calcification and tumor-like calcium deposits around joints. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of associated disease.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProtFamilial multiple endocrine neoplasia type I
0
Active trials
21
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.85
LOEUF
DN
Mechanism· predicted
Clinical SummarySCG2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.85LOEUF
pLI 0.000
Z-score 2.07
OE 0.52 (0.320.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.08Z-score
OE missense 1.01 (0.921.11)
320 obs / 316.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.52 (0.320.85)
00.351.4
Missense OE1.01 (0.921.11)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 11 / 21.3Missense obs/exp: 320 / 316.2Syn Z: -0.53
DN
0.74top 25%
GOF
0.4579th %ile
LOF
0.2385th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SCG2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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