GeneBe

AIP

protein-coding

aryl hydrocarbon receptor interacting protein, the group of FKBP prolyl isomerases|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

MANE transcript

NM_003977.4

Inheritance

AD

ClinVar variants

P:75U:639B:357

Top phenotype

Pituitary adenoma 1, multiple types

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr11:67,468,174-67,491,154

External References & Databases

Ensembl (ENSG00000110711)NCBI Gene (9049)OMIM (605555)HGNC:358GenCCUniProt (O00170)AlphaFoldClinVar (AIP)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~23.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pituitary gigantismSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020479

Submitter: Orphanet

familial isolated pituitary adenomaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0017824

Submitter: Orphanet

acromegalySUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0019933

Submitter: Orphanet

growth hormone secreting pituitary adenoma 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007052

Submitter: Labcorp Genetics (formerly Invitae)

growth hormone secreting pituitary adenoma 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007052

Submitter: PanelApp Australia

growth hormone secreting pituitary adenoma 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007052

Submitter: G2P

Clinical Genomic Database (CGD)

Pituitary adenoma 1, multiple typesAD

Manifestation: Endocrine; Oncologic

Intervention: Endocrine; Oncologic

Rationale: Surveillance and/or awareness of cancer risk may allow early diagnosis of pituitary tumors (as well as related manifestations, such as hypertension, hypogonadism, diabetes mellitus, and osteoporosis), which could potentially be beneficial to allow early medical (eg, with somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) or surgical treatment; Surveillance post-treatment may also be beneficial to detect recurrence/new adenomas

Comments: Multiple tumor types have been described

Refs: 7621566; 11158006; 16728643; 17299063; 22319033; 17609395; 17244780; 17360484; 17341560; 18381572; 20570174; 20685857; 19945022; 20506337; 20507346; 21591954; 21753072; 22319033; 22720333; 22612670; 23270713; 23321498; 23674160; 23743763; 24078436Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AIP variants in ClinVar

11 Conditions Cataloged
Hereditary cancer-predisposing syndromeTotal: 872
not providedTotal: 828
Somatotroph adenomaTotal: 153
AIP-related disorderTotal: 32
not specifiedTotal: 21
Familial isolated pituitary adenomaTotal: 12
Pituitary dependent hypercortisolismTotal: 6
Pituitary adenoma predispositionTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003977.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
13
clinvar
309
clinvar
3
clinvar
 325
missense
2
clinvar
601
clinvar
42
clinvar
2
clinvar
 647
nonsense
27
clinvar
2
clinvar
6
clinvar
 35
start loss
4
clinvar
1
clinvar
 5
frameshift
26
clinvar
6
clinvar
11
clinvar
 43
splice donor/acceptor (+/-2bp)
8
clinvar
7
clinvar
1
clinvar
 16
Total532263935251071

Highest pathogenic variant AF is 0.00001426507

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003977.4RefSeqNP_003968.36MANE Select
ENST00000279146.8EnsemblENSP00000279146.36MANE Select
NM_001302959.2RefSeqNP_001289888.15Standard
NM_001302960.2RefSeqNP_001289889.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cushing,s syndrome - Homo sapiens (human)
  • Aryl Hydrocarbon Receptor
  • Aryl Hydrocarbon Receptor Pathway
  • Nuclear Receptors Meta-Pathway
  • Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation

Biological Process

  • protein targeting to mitochondrion
  • xenobiotic metabolic process
  • regulation of protein kinase A signaling
  • protein maturation by protein folding
  • interleukin-12-mediated signaling pathway

Molecular Function

  • transcription coactivator activity
  • protein binding
  • transcription factor binding
  • aryl hydrocarbon receptor binding
  • GAF domain binding

Cellular Component

  • nucleoplasm
  • cytoplasm
  • cytosol
  • plasma membrane
  • aryl hydrocarbon receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000279146
Coding exons
6
Length
8063
Individuals with no LoFs
125710
Homozygous LoFs
0
Heterozygous LoFs
12
Defined
125722
p
0.0000477
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.9301732110.8200.00001402159
Missense (PolyPhen)5383.810.63238916
Synonymous-0.1739289.91.020.00000631643
Loss of Function3.01417.70.2269.38e-7174

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000320.00032rare
European (Non-Finnish)0.0000360.000035rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.;
Disease
DISEASE: Prolactin-secreting pituitary adenoma (PSPA) [MIM:600634]: Most common type of hormonally active pituitary adenoma. {ECO:0000269|PubMed:16728643, ECO:0000305|PubMed:17244780}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.133

Intolerance Scores

LoFtool
0.171
RVIS EVS
-0.14
RVIS percentile EVS
43.77

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.960

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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