IL17D

Chr 13

interleukin 17D

Also known as: IL-17D

NCBI Gene: 53342 ENSG00000172458 UniProt: Q8TAD2

The protein is a cytokine that induces expression of IL6, IL8, and GM-CSF from endothelial cells. Mutations cause autosomal recessive combined immunodeficiency with susceptibility to viral infections and hypogammaglobulinemia. The gene is not highly constrained against loss-of-function variation, which is consistent with the recessive inheritance pattern observed in affected individuals.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.198

Z-score 0.98

OE 0.36 (0.13–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.26Z-score

OE missense 1.09 (0.91–1.31)

80 obs / 73.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.36 (0.13–1.54)

0≤0.351.4

Missense OE?1.09 (0.91–1.31)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 1 / 2.7Missense obs/exp: 80 / 73.7Syn Z: -0.56

Background carrier burden — how many people carry a rare variant somewhere in IL17D?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

386 rare PASS variants

Rare truncating (LoF)

1 in 530

82 rare PASS variants

Rare synonymous (reference)

1 in 220

183 rare PASS variants

Rare missense and truncating variants are carried at similar rates in IL17D; this gene does not show strong loss-of-function constraint by this measure. 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 260	1 in 460
South Asian	~43k	1 in 150	1 in 1,000
Remaining (unassigned)	~30k	1 in 140	1 in 850
European (Finnish)	~26k	1 in 380	≈ 1 in 8,100
Admixed American	~22k	1 in 130	1 in 470
African / African American	~21k	1 in 170	1 in 350
East Asian	~20k	1 in 120	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 840	none seen
Middle Eastern	~2,884	1 in 200	≈ 1 in 770

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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 1 of 2 (exon 1 below).? see exons ↓