SERPINC1

Chr 1

serpin family C member 1

Also known as: AT3, AT3D, ATIII, ATIII-R2, ATIII-T1, ATIII-T2, THPH7

NCBI Gene: 462ENSG00000117601UniProt: P01008

The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAntithrombin III deficiency

Clinical highlights

Gene-disease validity (ClinGen)
hereditary antithrombin deficiency · SDDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
4
Active trials
62
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.15
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
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GeneReview available — SERPINC1
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.15LOEUF
pLI 0.999
Z-score 4.12
OE 0.00 (0.00–0.15)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.36Z-score
OE missense 0.76 (0.68–0.86)
199 obs / 260.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.15)
0≤0.351.4
Missense OE?0.76 (0.68–0.86)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 0 / 19.8Missense obs/exp: 199 / 260.7Syn Z: 0.05

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SERPINC1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients