SIPA1

Chr 11

signal-induced proliferation-associated 1

ENSG00000213445UniProt: Q96FS4

GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state (PubMed:9346962). Affects cell cycle progression (By similarity)

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SIPA1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.51LOEUF
pLI 0.005
Z-score 3.83
OE 0.31 (0.19–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.46Z-score
OE missense 0.72 (0.67–0.78)
445 obs / 616.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.19–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.67–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 11 / 35.7Missense obs/exp: 445 / 616.8Syn Z: 1.94

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SIPA1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dynamic relationship between SIPA1 gene and protein expression and the development of gastric cancer.
Li JY et al.·Genet Mol Res
2017
The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype, lymph node status and survival in a group of Lithuanian young breast cancer patients.
Ugenskienė R et al.·Biomarkers
2016Cohort
[Expression of SIPA1 in colorectal cancer and its impact on its biological behavior].
Wang NZ et al.·Zhonghua Zhong Liu Za Zhi
2025
A multiethnic whole genome sequencing study to identify novel loci for bone mineral density.
Greenbaum J et al.·Hum Mol Genet
2022Meta-analysis
A novel nuclear localization region in SIPA1 determines protein nuclear distribution and epirubicin-sensitivity of breast cancer cells.
Ma Y et al.·Int J Biol Macromol
2021
Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer.
Crawford NP et al.·Breast Cancer Res
2006
Sipa1 promoter polymorphism predicts risk and metastasis of lung cancer in Chinese.
Xie C et al.·Mol Carcinog
2013
Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility.
Hsieh SM et al.·BMC Cancer
2009
Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer.
Brooks R et al.·Gynecol Oncol
2010
An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation.
Rothe M et al.·Development
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools