AHR

aryl hydrocarbon receptor, the group of Basic helix-loop-helix proteins|PAS domain containing

Basic information

Region (hg38): 7:16916359-17346152

Links

ENSG00000106546 ∙ NCBI:196 ∙ OMIM:600253 ∙ HGNC:348 ∙ Uniprot:P35869 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• foveal hypoplasia (Limited), mode of inheritance: AR
• retinitis pigmentosa 85 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 85	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	29726989

ClinVar

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

• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AHR 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			1	112	4	117
missense			241	6	5	252
nonsense	2					2
start loss			1			1
frameshift	2		1			3
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)		1				1
splice region			5	6	2	13
non coding			3	38		41
Total	4	1	249	157	9

Highest pathogenic variant AF is 0.0000132

Variants in AHR

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

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

Position	Type	Phenotype	Significance	ClinVar
7-17296620-TTAAGG-T			Benign (Aug 01, 2024)
7-17299265-A-G			Uncertain significance (Mar 15, 2022)
7-17299271-A-G			Uncertain significance (Apr 24, 2021)
7-17299272-G-C			Uncertain significance (Apr 10, 2022)
7-17299283-A-G		not specified	Uncertain significance (Nov 29, 2023)
7-17299284-A-G			Uncertain significance (Jul 26, 2022)
7-17299299-G-A			Uncertain significance (Aug 26, 2021)
7-17299302-G-T			Uncertain significance (Jun 27, 2022)
7-17299315-G-A			Likely benign (Jul 18, 2021)
7-17299328-A-T			Uncertain significance (Sep 03, 2021)
7-17299343-G-A			Likely benign (Feb 15, 2021)
7-17299343-GC-TT			Uncertain significance (Apr 13, 2023)
7-17299346-C-T			Likely benign (Jan 21, 2022)
7-17309919-TTTTG-T			Likely benign (Jan 22, 2024)
7-17309923-G-A			Likely benign (Sep 25, 2022)
7-17309944-C-A			Uncertain significance (Jul 29, 2022)
7-17309945-A-C			Likely benign (Apr 08, 2021)
7-17309974-C-T		not specified	Uncertain significance (Feb 22, 2023)
7-17309978-C-G			Likely benign (Jun 28, 2022)
7-17309981-G-A			Likely benign (Nov 27, 2023)
7-17309982-C-A			Likely benign (Mar 04, 2022)
7-17309984-G-A			Likely benign (Mar 13, 2022)
7-17309994-C-A			Likely benign (Jul 10, 2022)
7-17310002-T-C		AHR-related disorder	Benign (Jan 31, 2024)
7-17310004-C-T			Uncertain significance (Sep 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AHR	protein_coding	protein_coding	ENST00000242057	11	47531

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000109	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.735	403	447	0.902	0.0000223	5619
Missense in Polyphen		56	101.24	0.55314		1270
Synonymous	-1.01	179	163	1.10	0.00000842	1573
Loss of Function	5.64	2	40.9	0.0489	0.00000238	449

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000939	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000187	0.000185
European (Non-Finnish)	0.0000268	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000656	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1. The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:10395741, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:7961644}.
• Pathway: Cushing,s syndrome - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Integrated Breast Cancer Pathway;Adipogenesis;Aryl Hydrocarbon Receptor;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Cannabinoid receptor signaling;Development and heterogeneity of the ILC family;ahr signal transduction pathway;Aryl hydrocarbon receptor signalling;Phase I - Functionalization of compounds;Endogenous sterols;Xenobiotics;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;AndrogenReceptor (Consensus)

Recessive Scores

• pRec: 0.740

Intolerance Scores

• loftool: 0.393
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.23

Haploinsufficiency Scores

• pHI: 0.439
• hipred: Y
• hipred_score: 0.707
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.714

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ahr
• 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; neoplasm; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: blood vessel development;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;xenobiotic metabolic process;apoptotic process;cell cycle;response to xenobiotic stimulus;response to toxic substance;regulation of gene expression;cAMP-mediated signaling;intracellular receptor signaling pathway;regulation of B cell proliferation;circadian regulation of gene expression;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cellular response to cAMP;cellular response to forskolin;cellular response to 2,3,7,8-tetrachlorodibenzodioxine
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;protein-containing complex;cytosolic aryl hydrocarbon receptor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;TFIID-class transcription factor complex binding;transcription coactivator binding;DNA binding;DNA-binding transcription factor activity;aryl hydrocarbon receptor activity;nuclear receptor activity;protein binding;transcription factor binding;TBP-class protein binding;enhancer binding;protein homodimerization activity;transcription regulatory region DNA binding;protein heterodimerization activity;protein dimerization activity;Hsp90 protein binding;E-box binding;sequence-specific double-stranded DNA binding