S100G

Chr X

S100 calcium binding protein G

Also known as: CABP, CABP1, CABP9K, CALB3

NCBI Gene: 795 ENSG00000169906 UniProt: P29377

Calbindin D9K is a vitamin D-dependent calcium-binding protein that buffers cytoplasmic calcium and facilitates ATP-dependent calcium transport, particularly in intestinal absorption. Mutations in S100G cause autosomal recessive congenital cataracts, facial dysmorphism, and neuropathy (CCFDN), a disorder affecting the eyes, nervous system, and facial development. This gene is not highly constrained against loss-of-function variants, and the condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq

This gene encodes calbindin D9K, a vitamin D-dependent calcium-binding protein. This cytosolic protein belongs to a family of calcium-binding proteins that includes calmodulin, parvalbumin, troponin C, and S100 protein. In the intestine, the protein is vitamin D-dependent and its expression correlates with calcium transport activity. The protein may increase Ca2+ absorption by buffering Ca2+ in the cytoplasm and increase ATP-dependent Ca2+ transport in duodenal basolateral membrane vesicles. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.84

Clinical Summary— S100G

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Population Constraint (gnomAD)

Low constraint (pLI 0.11) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 VUS of 9 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.84LOEUF

pLI 0.115

Z-score 0.35

OE 0.69 (0.21–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.38Z-score

OE missense 0.78 (0.54–1.15)

18 obs / 23.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.21–1.84)

0≤0.351.4

Missense OE?0.78 (0.54–1.15)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 1 / 1.5Missense obs/exp: 18 / 23.1Syn Z: 0.37

This gene — mechanism propensity

0.75top 25%

GOF

0.76top 25%

LOF

0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

9 submitted variants in ClinVar

ClinVar

Classification Summary

VUS3

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	3	0	3
Likely Benign	0	1	1
Benign	0	0	0
Total	3	1	4

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

View in ClinVar →

84 pathogenic / likely-pathogenic (of 91) ClinVar copy-number / structural variants overlap S100G — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →