PLSCR1

Chr 3

phospholipid scramblase 1

Also known as: MMTRA1B

NCBI Gene: 5359 ENSG00000188313 UniProt: O15162 OMIM: 604170

This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.73

Clinical Summary— PLSCR1

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 VUS of 45 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?

0.73LOEUF

pLI 0.012

Z-score 2.35

OE 0.37 (0.20–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.81 (0.71–0.94)

137 obs / 168.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.20–0.73)

0≤0.351.4

Missense OE?0.81 (0.71–0.94)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 16.2Missense obs/exp: 137 / 168.6Syn Z: 0.45

This gene — mechanism propensity

0.81top 10%

GOF

0.76top 25%

LOF

0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	2	22	0	24
Likely Benign	0	1	1	2
Benign	0	0	0	0
Total	2	23	1	26

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap PLSCR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →