FSTL5

Chr 4

follistatin like 5

NCBI Gene: 56884 ENSG00000168843 UniProt: Q8N475 OMIM: 620128

FSTL5 encodes a protein that binds calcium ions and regulates BMP signaling pathway activity in the extracellular region, participating in cell differentiation processes. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.63), but no definitive human disease associations have been established to date.

OMIM ResearchSummary from RefSeq

Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation and regulation of BMP signaling pathway. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.42

OE 0.42 (0.29–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.92–1.08)

426 obs / 428.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.29–0.63)

0≤0.351.4

Missense OE?0.99 (0.92–1.08)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 17 / 40.5Missense obs/exp: 426 / 428.7Syn Z: -0.25

Background carrier burden — how many people carry a rare variant somewhere in FSTL5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 61

1,154 rare PASS variants

Rare truncating (LoF)

1 in 1,700

131 rare PASS variants

Rare synonymous (reference)

1 in 120

409 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FSTL5. 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 85	1 in 2,000
South Asian	~43k	1 in 47	1 in 2,100
Remaining (unassigned)	~30k	1 in 49	1 in 2,300
European (Finnish)	~27k	1 in 140	1 in 5,300
Admixed American	~22k	1 in 44	1 in 1,800
African / African American	~21k	1 in 46	1 in 1,100
East Asian	~20k	1 in 74	1 in 1,500
Ashkenazi Jewish	~13k	1 in 110	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 52	≈ 1 in 2,900

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): 7 of 15 coding exons well covered in gnomAD exomes; exons 3, 5, 6, 7, 9 and 3 more marginal. Genomes: all 15.? see exons ↓