PROS1

Chr 3ADAR

protein S

Also known as: PROS, PS21, PS22, PS23, PS24, PS25, PSA, THPH5

This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. It is found in plasma in both a free, functionally active form and also in an inactive form complexed with C4b-binding protein. Mutations in this gene result in autosomal dominant hereditary thrombophilia. An inactive pseudogene of this locus is located at an adjacent region on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Oct 2015]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Thrombophilia 5 due to protein S deficiency, autosomal dominantMIM #612336
AD
Thrombophilia 5 due to protein S deficiency, autosomal recessiveMIM #614514
AR
UniProtThrombophilia due to protein S deficiency, autosomal dominant
UniProtThrombophilia due to protein S deficiency, autosomal recessive

Clinical highlights

Gene-disease validity (ClinGen)
protein S deficiency · SDDefinitivesufficient evidence for diagnostic panels
3
Active trials
77
Pubs (1 yr)
P/LP submissions
P/LP missense
0.57
LOEUF
DN
Mechanism· predicted
📖
GeneReview available — PROS1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.57LOEUF
pLI 0.000
Z-score 3.49
OE 0.35 (0.230.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.58Z-score
OE missense 0.91 (0.831.00)
335 obs / 366.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.35 (0.230.57)
00.351.4
Missense OE?0.91 (0.831.00)
00.61.4
Synonymous OE?0.99
01.21.6
LoF obs/exp: 12 / 34.0Missense obs/exp: 335 / 366.5Syn Z: 0.11

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PROS1 · protein map & ClinVar variants

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