ARNT2

aryl hydrocarbon receptor nuclear translocator 2, the group of Basic helix-loop-helix proteins|PAS domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:80404349-80597933

Links

ENSG00000172379 ∙ NCBI:9915 ∙ OMIM:606036 ∙ HGNC:16876 ∙ Uniprot:Q9HBZ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Webb-Dattani syndrome (Limited), mode of inheritance: AR
• septooptic dysplasia (Supportive), mode of inheritance: AD
• Webb-Dattani syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Webb-Datani syndrome	AR	Endocrine; Renal	The condition may involve multiple pituitary hormone deficiencies, and awareness may allow early recognition and treatment; Awareness of the risk of renal manifestations such as hydronephrosis and vesicoureteral reflux may allow surveillance and renal-protective measures	Craniofacial; Endocrine; Neurologic; Ophthalmologic; Renal	24022475

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARNT2 gene.

• not provided (138 variants)
• Inborn genetic diseases (21 variants)
• Webb-Dattani syndrome (14 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARNT2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	42	8	53
missense			69	3	1	73
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1	1	5	2	9
non coding				18	10	28
Total	1	0	72	63	19

Variants in ARNT2

This is a list of pathogenic ClinVar variants found in the ARNT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-80404522-A-G			Uncertain significance (Jun 04, 2022)
15-80404523-C-A		not specified	Uncertain significance (Dec 01, 2022)
15-80404524-C-T			Likely benign (Jun 14, 2018)
15-80404533-G-C			Likely benign (Jul 17, 2022)
15-80404543-C-T			Uncertain significance (Sep 27, 2022)
15-80410644-A-G		Pulmonary disease, chronic obstructive, susceptibility to	association (May 13, 2022)
15-80441756-C-T		Pulmonary disease, chronic obstructive, susceptibility to	association (May 12, 2022)
15-80450910-C-T		not specified	Uncertain significance (Nov 22, 2022)
15-80450914-G-T			Uncertain significance (Jun 16, 2022)
15-80450917-C-T			Likely benign (Mar 18, 2022)
15-80450938-C-T			Likely benign (Sep 27, 2022)
15-80450939-G-A		not specified	Uncertain significance (Jul 25, 2023)
15-80450945-G-A		not specified	Uncertain significance (Oct 12, 2021)
15-80450945-G-C			Uncertain significance (Mar 27, 2022)
15-80450959-G-A			Uncertain significance (Jul 20, 2022)
15-80450972-C-T			Uncertain significance (Jun 17, 2022)
15-80450973-G-A			Uncertain significance (Mar 27, 2022)
15-80450973-G-C		not specified	Uncertain significance (Feb 27, 2023)
15-80450985-G-A			Uncertain significance (Dec 02, 2021)
15-80451009-C-T			Benign (Jan 26, 2024)
15-80451010-G-A			Likely benign (Sep 27, 2022)
15-80451013-T-C			Likely benign (Oct 28, 2023)
15-80457938-C-T			Likely benign (Mar 27, 2022)
15-80457944-T-C			Likely benign (Dec 27, 2022)
15-80470185-TC-T		Webb-Dattani syndrome	Benign (Jul 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARNT2	protein_coding	protein_coding	ENST00000303329	19	193587

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00858	125732	0	15	125747	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	322	439	0.734	0.0000264	4723
Missense in Polyphen		25	40.916	0.61101		364
Synonymous	0.312	166	171	0.970	0.0000112	1378
Loss of Function	5.04	6	40.7	0.147	0.00000190	464

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.00	0.00
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function (PubMed:24022475). Specifically recognizes the xenobiotic response element (XRE). {ECO:0000269|PubMed:24022475}.
• Disease: DISEASE: Webb-Dattani syndrome (WEDAS) [MIM:615926]: A disorder characterized by postnatal microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, global developmental delay, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract. {ECO:0000269|PubMed:24022475}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Renal cell carcinoma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Type 2 papillary renal cell carcinoma;Aryl hydrocarbon receptor signalling;Phase I - Functionalization of compounds;Endogenous sterols;Xenobiotics;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.274
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

• pHI: 0.166
• hipred: Y
• hipred_score: 0.802
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Arnt2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: arnt2
• Affected structure: dopaminergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to hypoxia;in utero embryonic development;regulation of transcription, DNA-templated;xenobiotic metabolic process;central nervous system development;brain development;positive regulation of cell population proliferation;response to estradiol;negative regulation of apoptotic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;aryl hydrocarbon receptor binding;protein heterodimerization activity