LCP1

Chr 13

lymphocyte cytosolic protein 1

Also known as: CP64, HEL-S-37, L-PLASTIN, LC64P, PLS2

NCBI Gene: 3936 ENSG00000136167 UniProt: P13796

LCP1 encodes L-plastin, an actin-binding protein specifically expressed in hematopoietic cell lineages that modulates T-cell activation and regulates cell surface expression of activation markers including CD25 and CD69. Mutations cause autosomal recessive immunodeficiency with recurrent infections, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.399), reflecting its essential role in immune cell function.

ResearchSummary from RefSeq, UniProt

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.40

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.553

Z-score 4.19

OE 0.21 (0.12–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.72Z-score

OE missense 0.74 (0.66–0.82)

247 obs / 335.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.12–0.40)

0≤0.351.4

Missense OE?0.74 (0.66–0.82)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 7 / 33.0Missense obs/exp: 247 / 335.5Syn Z: 1.16

Background carrier burden — how many people carry a rare variant somewhere in LCP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

635 rare PASS variants

Rare truncating (LoF)

1 in 3,100

55 rare PASS variants

Rare synonymous (reference)

1 in 180

265 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LCP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 3,400
South Asian	~43k	1 in 90	≈ 1 in 15,000
Remaining (unassigned)	~30k	1 in 100	1 in 3,600
European (Finnish)	~27k	1 in 300	1 in 1,800
Admixed American	~22k	1 in 120	1 in 3,700
African / African American	~21k	1 in 110	1 in 3,800
East Asian	~20k	1 in 90	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 59	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓