IL12A

Chr 3

interleukin 12A

Also known as: CLMF, IL-12A, NFSK, NKSF1, P35

NCBI Gene: 3592 ENSG00000168811 UniProt: P29459

This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.047

Z-score 2.00

OE 0.36 (0.17–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.83Z-score

OE missense 0.80 (0.68–0.94)

108 obs / 135.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.17–0.81)

0≤0.351.4

Missense OE?0.80 (0.68–0.94)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 4 / 11.2Missense obs/exp: 108 / 135.2Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in IL12A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

294 rare PASS variants

Rare truncating (LoF)

1 in 13,000

29 rare PASS variants

Rare synonymous (reference)

1 in 320

116 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL12A. 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 310	1 in 11,000
South Asian	~43k	1 in 220	1 in 8,600
Remaining (unassigned)	~30k	1 in 280	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,900	≈ 1 in 27,000
Admixed American	~22k	1 in 370	none seen
African / African American	~21k	1 in 310	≈ 1 in 17,000
East Asian	~20k	1 in 190	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 360	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): 6 of 7 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 7.? see exons ↓