ARNT2

Chr 15

aryl hydrocarbon receptor nuclear translocator 2

Also known as: WEDAS, bHLHe1

NCBI Gene: 9915 ENSG00000172379 UniProt: Q9HBZ2

The protein is a transcription factor that forms heterodimeric complexes with sensor proteins to regulate genes involved in developmental and environmental responses, including hypoxia response and neurogenesis. Mutations cause Webb-Dattani syndrome, which affects the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function, with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), indicating intolerance to protein-disrupting mutations.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the basic-helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. The encoded protein acts as a partner for several sensor proteins of the bHLH-PAS family, forming heterodimers with the sensor proteins that bind regulatory DNA sequences in genes responsive to developmental and environmental stimuli. Under hypoxic conditions, the encoded protein complexes with hypoxia-inducible factor 1alpha in the nucleus and this complex binds to hypoxia-responsive elements in enhancers and promoters of oxygen-responsive genes. A highly similar protein in mouse forms functional complexes with both aryl hydrocarbon receptors and Single-minded proteins, suggesting additional roles for the encoded protein in the metabolism of xenobiotic compounds and the regulation of neurogenesis, respectively. [provided by RefSeq, Dec 2013]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWebb-Dattani syndrome

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — ARNT2

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ARNT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

813 rare PASS variants

Rare truncating (LoF)

1 in 3,200

78 rare PASS variants

Rare synonymous (reference)

1 in 130

390 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARNT2. 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 4,200
South Asian	~43k	1 in 79	1 in 1,600
Remaining (unassigned)	~30k	1 in 97	1 in 6,000
European (Finnish)	~27k	1 in 220	1 in 2,000
Admixed American	~22k	1 in 100	1 in 3,900
African / African American	~21k	1 in 92	≈ 1 in 8,400
East Asian	~20k	1 in 81	1 in 520
Ashkenazi Jewish	~13k	1 in 650	1 in 870
Middle Eastern	~2,884	1 in 86	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.