SIAH2

Chr 3

siah E3 ubiquitin protein ligase 2

Also known as: hSiah2

This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.59
Clinical SummarySIAH2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
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ClinVar Variants
29 VUS of 35 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.59LOEUF
pLI 0.687
Z-score 2.31
OE 0.12 (0.040.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.43Z-score
OE missense 0.48 (0.400.57)
81 obs / 170.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.040.59)
00.351.4
Missense OE?0.48 (0.400.57)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 1 / 8.1Missense obs/exp: 81 / 170.1Syn Z: 0.23

This gene — mechanism propensity

DN
0.4289th %ile
GOF
0.4481th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

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

ClinVar Variant Classifications

35 submitted variants in ClinVar

Classification Summary

VUS29
Benign2
29
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
29
0
0
29
Likely Benign
0
0
0
0
0
Benign
0
0
0
2
2
Total0290231

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap SIAH2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SIAH2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →