S100A14

Chr 1

S100 calcium binding protein A14

Also known as: BCMP84, S100A15

NCBI Gene: 57402 ENSG00000189334 UniProt: Q9HCY8 OMIM: 607986

This gene encodes a member of the S100 protein family which contains an EF-hand motif and binds calcium. The gene is located in a cluster of S100 genes on chromosome 1. Levels of the encoded protein have been found to be lower in cancerous tissue and associated with metastasis suggesting a tumor suppressor function (PMID: 19956863, 19351828). [provided by RefSeq, Dec 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.81

Clinical Summary— S100A14

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

21 VUS of 25 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.002

Z-score 0.10

OE 0.95 (0.46–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.08 (0.89–1.33)

66 obs / 61.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.46–1.81)

0≤0.351.4

Missense OE?1.08 (0.89–1.33)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 4.2Missense obs/exp: 66 / 61.1Syn Z: 0.13

This gene — mechanism propensity

0.76top 25%

GOF

0.86top 5%

LOF

0.2189th %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

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	21	21
Likely Benign	0	0
Benign	0	0
Total	21	21

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap S100A14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →