FGL1

Chr 8

fibrinogen like 1

Also known as: HFREP1, HP-041, HPS, LFIRE-1, LFIRE1

NCBI Gene: 2267 ENSG00000104760 UniProt: Q08830 OMIM: 605776

Fibrinogen-like 1 encodes a secreted protein that inhibits T-cell activation by binding to the LAG3 receptor and also promotes hepatocyte growth. This gene is not constrained against loss-of-function variants and is not currently associated with any established Mendelian disorders in pediatric neurology.

OMIM ResearchSummary from RefSeq, UniProt

Fibrinogen-like 1 is a member of the fibrinogen family. This protein is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of fibrinogens and fibrinogen related proteins. However, this protein lacks the platelet-binding site, cross-linking region and a thrombin-sensitive site which are necessary for fibrin clot formation. This protein may play a role in the development of hepatocellular carcinomas. Four alternatively spliced transcript variants encoding the same protein exist for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.93

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.000

Z-score -2.43

OE 1.60 (1.18–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.72Z-score

OE missense 1.59 (1.44–1.76)

266 obs / 167.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.60 (1.18–1.93)

0≤0.351.4

Missense OE?1.59 (1.44–1.76)

0≤0.61.4

Synonymous OE?1.75

0≤1.21.6

LoF obs/exp: 31 / 19.4Missense obs/exp: 266 / 167.2Syn Z: -4.54

Background carrier burden — how many people carry a rare variant somewhere in FGL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

639 rare PASS variants

Rare truncating (LoF)

1 in 1,000

103 rare PASS variants

Rare synonymous (reference)

1 in 270

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FGL1. 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 110	1 in 600
South Asian	~43k	1 in 91	1 in 350
Remaining (unassigned)	~30k	1 in 66	1 in 1,100
European (Finnish)	~27k	1 in 470	≈ 1 in 13,000
Admixed American	~22k	1 in 78	1 in 1,400
African / African American	~21k	1 in 57	1 in 520
East Asian	~20k	1 in 59	1 in 990
Ashkenazi Jewish	~13k	1 in 670	1 in 1,400
Middle Eastern	~2,884	1 in 82	≈ 1 in 710

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓