AIS
MCID: AND002
MIFTS: 63

Androgen Insensitivity Syndrome (AIS)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Androgen Insensitivity Syndrome

MalaCards integrated aliases for Androgen Insensitivity Syndrome:

Name: Androgen Insensitivity Syndrome 57 12 73 25 20 43 58 72 36 54 15
Androgen Resistance Syndrome 12 43 58 72 29 6 32
Androgen Receptor Deficiency 57 20 43 72 70
Ais 57 20 43 58 72
Dihydrotestosterone Receptor Deficiency 57 20 43 72
Testicular Feminization Syndrome 57 12 58 72
Dhtr Deficiency 57 20 43 72
Testicular Feminization 12 25 70
Ar Deficiency 57 43 72
Androgen-Insensitivity Syndrome 12 70
Goldberg-Maxwell Syndrome 12 58
Androgen Insensitivity 57 13
Tfm 57 72
Complete Androgen Insensitivity Syndrome 72
Testicular Feminization Syndrome; Tfm 57
Syndrome, Insensitivity, Androgen 39
Goldberg - Maxwell Syndrome 12
Androgen Insensitivity Nos 70
Feminisation - Testicular 12
Morris Syndrome 58
Cais 72
Ary 73
Ar 48

Characteristics:

Orphanet epidemiological data:

58
androgen insensitivity syndrome
Inheritance: X-linked recessive; Age of onset: Antenatal,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
x-linked recessive

Miscellaneous:
presents with inguinal hernia (prepubertal) or primary amenorrhea (post pubertal)
incidence 1/20,000-1/64,000 male births


HPO:

31
androgen insensitivity syndrome:
Inheritance x-linked recessive inheritance


GeneReviews:

25
Penetrance No definitive data regarding penetrance exist, possibly because of under-ascertainment of affected individuals, particularly phenotypic but infertile males in whom ar molecular genetic testing may not be performed [gottlieb et al 2005]. the problem is compounded by situations where there is a genotype-phenotype disconnect and when individuals with features of ais are not found to have an identifiable ar pathogenic variant.

Classifications:

Orphanet: 58  
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:4674
OMIM® 57 300068
KEGG 36 H02177
ICD9CM 34 259.51
MeSH 44 D013734
NCIt 50 C27226
SNOMED-CT 67 12313004
ICD10 32 E34.5
MESH via Orphanet 45 D013734
ICD10 via Orphanet 33 E34.5
UMLS via Orphanet 71 C0039585 C0936016
Orphanet 58 ORPHA754
MedGen 41 C0039585
UMLS 70 C0039585 C0936016 C2713546 more

Summaries for Androgen Insensitivity Syndrome

MedlinePlus Genetics : 43 Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X chromosome and one Y chromosome in each cell. Because their bodies are unable to respond to certain male sex hormones (called androgens), they may have mostly female external sex characteristics or signs of both male and female sexual development.Complete androgen insensitivity syndrome occurs when the body cannot use androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive a child (infertile). They are typically raised as females and have a female gender identity. Affected individuals have male internal sex organs (testes) that are undescended, which means they are abnormally located in the pelvis or abdomen. Undescended testes have a small chance of becoming cancerous later in life if they are not surgically removed. People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic area and under the arms.The partial and mild forms of androgen insensitivity syndrome result when the body's tissues are partially sensitive to the effects of androgens. People with partial androgen insensitivity (also called Reifenstein syndrome) can have genitalia that look typically female, genitalia that have both male and female characteristics, or genitalia that look typically male. They may be raised as males or as females and may have a male or a female gender identity. People with mild androgen insensitivity are born with male sex characteristics, but they are often infertile and tend to experience breast enlargement at puberty.

MalaCards based summary : Androgen Insensitivity Syndrome, also known as androgen resistance syndrome, is related to androgen insensitivity, partial and hypospadias 1, x-linked. An important gene associated with Androgen Insensitivity Syndrome is AR (Androgen Receptor), and among its related pathways/superpathways are Translation Non-genomic (rapid) action of Androgen Receptor and Nuclear Receptor transcription pathway. The drugs Fibrin Tissue Adhesive and Hormones have been mentioned in the context of this disorder. Affiliated tissues include testes, uterus and prostate, and related phenotypes are delayed puberty and cryptorchidism

Disease Ontology : 12 A disorder of sexual developement that is characterized by the inability of the cell to respond to androgens in individuals with a karyotype of 46,XY resulting in female physical traits but male genetic makeup.

GARD : 20 Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X chromosome and one Y chromosome in each cell. Because their bodies are unable to respond to certain male sex hormones (called androgens), they may have some physical traits of a woman. Androgen insensitivity syndrome is caused by mutations in the AR gene and is inherited in an X-linked recessive pattern.

OMIM® : 57 The androgen insensitivity syndrome is an X-linked recessive disorder in which affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal male 46,XY karyotype. Partial androgen insensitivity (PAIS; 312300), also called Reifenstein syndrome, results in hypospadias and micropenis with gynecomastia. (300068) (Updated 20-May-2021)

KEGG : 36 Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. AIS represents a spectrum of defects in androgen action. Pathogenesis is the result of mutations in the X-linked androgen receptor (AR) gene, which encodes for the ligand-activated androgen receptor.

UniProtKB/Swiss-Prot : 72 Androgen insensitivity syndrome: An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.

Wikipedia : 73 Androgen insensitivity syndrome (AIS) is an intersex condition with an estimated prevalence of about... more...

GeneReviews: NBK1429

Related Diseases for Androgen Insensitivity Syndrome

Diseases related to Androgen Insensitivity Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 305)
# Related Disease Score Top Affiliating Genes
1 androgen insensitivity, partial 33.3 SRD5A1 SHBG LYVE1 AR
2 hypospadias 1, x-linked 32.7 LOC109504725 AR
3 complete androgen insensitivity syndrome 32.4 SRY SHBG PTGDS NR1H2 MUC5AC MUC1
4 amenorrhea 31.8 SHBG NR5A1 INS
5 spinal and bulbar muscular atrophy, x-linked 1 31.7 LYVE1 LOC109504725 AR
6 gonadal dysgenesis 31.3 SRY SHBG NR5A1
7 pseudohermaphroditism 31.2 SRY SRD5A2 SRD5A1 NR5A1 AR
8 hypospadias 31.2 SRY SRD5A2 SRD5A1 NR5A1 MAMLD1 AR
9 penis agenesis 31.2 SRD5A2 SRD5A1 CGA AR
10 disorder of sexual development 31.1 SRD5A2 SHBG NR5A1 MAMLD1 INS AR
11 sertoli cell tumor 31.0 NR5A1 MUC1 AR
12 gynecomastia 31.0 SRY SRD5A2 SRD5A1 SHBG CGA AR
13 infertility 31.0 SHBG NR5A1 INS CGA AR
14 aromatase excess syndrome 30.9 SHBG NR5A1 INS AR
15 hermaphroditism 30.7 SRY SRD5A2 SHBG CGA AR
16 sexual disorder 30.7 SHBG INS AR
17 alopecia 30.6 SRD5A2 SRD5A1 SHBG AR
18 46,xy sex reversal 30.6 SRY SRD5A2 NR5A1 INS AR
19 hypogonadotropic hypogonadism 30.6 SHBG NR5A1 INS AR
20 cryptorchidism, unilateral or bilateral 30.6 SRD5A2 SRD5A1 SHBG NR5A1 MAMLD1 INS
21 transsexualism 30.6 SRD5A2 AR
22 mixed gonadal dysgenesis 30.5 SRY SRD5A1 NR5A1
23 prostatic adenoma 30.4 SRD5A1 SHBG AR
24 alopecia, androgenetic, 1 30.4 SRD5A2 SRD5A1 SHBG AR
25 prostatic hyperplasia, benign 30.4 SRD5A2 SRD5A1 AR
26 polycystic ovary syndrome 30.3 SRD5A1 SHBG INS IGF2 CGA AR
27 impotence 30.3 SRD5A1 SHBG INS
28 turner syndrome 30.3 SRY SHBG INS IGF2 AR
29 prostatic hypertrophy 30.3 SRY SRD5A2 SRD5A1 AR
30 germ cell cancer 30.2 IGF2 CGA AR
31 kallmann syndrome 30.2 SRD5A2 SHBG NR5A1 CGA
32 wilms tumor 1 30.1 SRY NR5A1 MUC1 IGF2 AR
33 androgenic alopecia 30.0 SRD5A2 SRD5A1 SHBG PTGDS INS AR
34 prostate cancer 29.4 SRD5A2 SRD5A1 SHBG NR1H2 NCOA2 MUC1
35 androgen insensitivity syndrome, mild 11.5
36 scoliosis, isolated 1 11.3
37 mayer-rokitansky-kuster-hauser syndrome 11.2
38 hypospadias 2, x-linked 11.2
39 pediatric arterial ischemic stroke 11.1
40 vitreoretinochoroidopathy 11.1
41 pulmonary fibrosis, idiopathic 10.9
42 pulmonary disease, chronic obstructive 10.9
43 patent ductus arteriosus 1 10.9
44 pulmonary hypertension 10.9
45 heart valve disease 10.9
46 pulmonary embolism 10.9
47 scoliosis 10.9
48 idiopathic scoliosis 10.8
49 inguinal hernia 10.7
50 infant gynecomastia 10.6

Graphical network of the top 20 diseases related to Androgen Insensitivity Syndrome:



Diseases related to Androgen Insensitivity Syndrome

Symptoms & Phenotypes for Androgen Insensitivity Syndrome

Human phenotypes related to Androgen Insensitivity Syndrome:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed puberty 58 31 hallmark (90%) Very frequent (99-80%) HP:0000823
2 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
3 male pseudohermaphroditism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000037
4 ambiguous genitalia, male 58 31 hallmark (90%) Very frequent (99-80%) HP:0000033
5 sparse axillary hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002215
6 absent axillary hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002221
7 sparse pubic hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002225
8 absent pubic hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002555
9 male infertility 58 31 hallmark (90%) Very frequent (99-80%) HP:0003251
10 aplasia/hypoplasia of the fallopian tube 58 31 hallmark (90%) Very frequent (99-80%) HP:0008655
11 aplasia/hypoplasia of the uterus 58 31 hallmark (90%) Very frequent (99-80%) HP:0008684
12 inguinal hernia 58 31 frequent (33%) Frequent (79-30%) HP:0000023
13 testicular neoplasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0010788
14 primary amenorrhea 31 HP:0000786
15 neoplasm 31 HP:0002664
16 abnormality of female internal genitalia 58 Very frequent (99-80%)
17 labial hypoplasia 31 HP:0000066
18 abnormality of the uterus 58 Very frequent (99-80%)
19 gynecomastia 31 HP:0000771
20 elevated circulating follicle stimulating hormone level 31 HP:0008232
21 female external genitalia in individual with 46,xy karyotype 31 HP:0008730
22 elevated circulating luteinizing hormone level 31 HP:0011969
23 absent facial hair 31 HP:0002550
24 blind vagina 31 HP:0040314
25 growth abnormality 31 HP:0001507

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary External Genitalia Male:
inguinal hernia
female external genitalia in males
underdeveloped labia
underdeveloped to normal clitoris

Skin Nails Hair Hair:
absent facial hair
sparse to absent axillary hair
sparse to absent pubic hair
luxuriant scalp hair

Growth Height:
tall for females (mean height 171.5cm)

Neoplasia:
sertoli cell adenomas
seminomas
malignant sex-cord stromal tumor

Chest Breasts:
gynecomastia

Genitourinary Internal Genitalia Male:
blind vagina
abdominal, inguinal, or labial testes

Growth Other:
female body habitus
female body fat distribution

Laboratory Abnormalities:
normal male karyotype (46,xy)
normal-elevated plasma testosterone (male range)
elevated plasma estrogen
elevated plasma luteinizing hormone (lh)
elevated plasma follicle stimulating hormone (fsh)

Clinical features from OMIM®:

300068 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Androgen Insensitivity Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.7 ALDH1A1 AR CGA IGF2 INS NCOA2
2 reproductive system MP:0005389 9.28 AR CGA IGF2 INS NCOA2 NR1H2

Drugs & Therapeutics for Androgen Insensitivity Syndrome

Drugs for Androgen Insensitivity Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 60)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Fibrin Tissue Adhesive Phase 3
2 Hormones Phase 3
3 Carboxyamido-triazole Phase 3
4 Calcium, Dietary Phase 3
5 calcium channel blockers Phase 3
6
Calcium Nutraceutical Phase 3 7440-70-2 271
7
Sargramostim Approved, Investigational Phase 2 123774-72-1, 83869-56-1
8
Metronidazole Approved Phase 2 443-48-1 4173
9
Flutamide Approved, Investigational Phase 2 13311-84-7 3397
10
Testosterone Approved, Investigational Phase 2 58-22-0 6013
11
Clotrimazole Approved, Vet_approved Phase 1, Phase 2 23593-75-1 2812
12
Miconazole Approved, Investigational, Vet_approved Phase 1, Phase 2 22916-47-8 4189
13
Bicalutamide Approved Phase 1, Phase 2 90357-06-5 56069 2375
14
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 5284616 6436030
15
Molgramostim Investigational Phase 2 99283-10-0
16 Protective Agents Phase 1, Phase 2
17 Fluorides Phase 1, Phase 2
18 Vaccines Phase 2
19 Samarium Sm-153 lexidronam Phase 2
20 Antiparasitic Agents Phase 2
21 Antiprotozoal Agents Phase 2
22 Analgesics Phase 2
23 Analgesics, Non-Narcotic Phase 2
24 polysaccharide-K Phase 2
25 Brewer's Yeast Phase 2
26 Antineoplastic Agents, Hormonal Phase 2
27 Androgens Phase 1, Phase 2
28 Hormone Antagonists Phase 1, Phase 2
29 Anti-Bacterial Agents Phase 1, Phase 2
30 Immunosuppressive Agents Phase 1, Phase 2
31 Antibiotics, Antitubercular Phase 1, Phase 2
32 Antifungal Agents Phase 1, Phase 2
33 Anti-Infective Agents Phase 1, Phase 2
34 Immunologic Factors Phase 1, Phase 2
35 Androgen Antagonists Phase 1, Phase 2
36 Dihydroxycholecalciferols Phase 2
37
Leucine Investigational, Nutraceutical Phase 2 61-90-5 6106
38
Arginine Investigational, Nutraceutical Phase 2 74-79-3 6322
39
Paclitaxel Approved, Vet_approved Phase 1 33069-62-4 36314
40
Ketoconazole Approved, Investigational Phase 1 65277-42-1 47576
41 Tubulin Modulators Phase 1
42 Albumin-Bound Paclitaxel Phase 1
43 Antimitotic Agents Phase 1
44 Cytochrome P-450 CYP3A Inhibitors Phase 1
45 Cytochrome P-450 Enzyme Inhibitors Phase 1
46
Hydrocortisone Approved, Vet_approved 50-23-7 5754
47
Hydrocortisone acetate Approved, Vet_approved 50-03-3
48
tannic acid Approved 1401-55-4
49
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
50 Hops Approved

Interventional clinical trials:

(show all 27)
# Name Status NCT ID Phase Drugs
1 A Randomised Clinical Trial Comparing a Novel Single-stage Autologous Cartilage Implantation System to Conventional Microfracture for Repair of Articular Cartilage Defects in the Knee Unknown status NCT01498029 Phase 3
2 Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Completed NCT00003869 Phase 3 carboxyamidotriazole
3 Measurement of Anti-Androgen Response Using Fluorine-18 Fluorocholine PET/CT in Androgen-Insensitive Prostate Cancer Completed NCT00928174 Phase 1, Phase 2 IV administration of fluorine-18 fluorocholine followed by PET/CT imaging
4 A Randomized Phase 2.5 Study of (153)Sm-EDTMP (Quadramet) With or Without a PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer Completed NCT00450619 Phase 2
5 A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer Completed NCT00450463 Phase 2 Sargramostim (GM-CSF, Leukine);Flutamide (Eulexin)
6 A Phase II Trial of Orally Administered CAI for Patients With Persistent or Refractory Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Completed NCT00019461 Phase 2 carboxyamidotriazole;chemotherapy
7 A Phase II Randomized Discontinuation Trial Of Carboxyaminoimidazole (CAI, NSC 609974) In Metastatic Renal Carcinoma Completed NCT00006486 Phase 2 carboxyamidotriazole
8 Phase II Study of Carboxyamidotriazole (CAI, NSC #609974) in Patients With Advanced Renal Cell Carcinoma Refractory to Immunotherapy Completed NCT00005045 Phase 2 carboxyamidotriazole
9 Phase II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) in Adults With Newly Diagnosed Glioblastoma Multiforme Completed NCT00004146 Phase 2 carboxyamidotriazole
10 Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer Terminated NCT01020305 Phase 1, Phase 2 Temsirolimus;Casodex (bicalutamide)
11 Phase II Trial of Zemplar (19-nor-1 a,25-Dihydroxyvitamin D2, Paricalcitol Capsule) on Bony Remodeling in Advanced Androgen-Insensitive Prostate Cancer Terminated NCT00634582 Phase 2 paricalcitol
12 An Open-Label, Phase I Dose Escalation Trial of MVA-BN®-PRO in Men With Androgen-Insensitive Prostate Cancer Completed NCT00629057 Phase 1
13 A PHASE I STUDY OF THE COMBINATION OF CAI AND PACLITAXEL IN ADULT PATIENTS WITH REFRACTORY CANCERS OR LYMPHOMA Completed NCT00019019 Phase 1 carboxyamidotriazole;paclitaxel
14 A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies Completed NCT00003249 Phase 1 carboxyamidotriazole;chemotherapy;ketoconazole
15 The Effect of Balance Training on Neuromuscular Control in Subjects With CAI Unknown status NCT03439930
16 Influence of Taping on Postural Control in Subjects With Chronic Ankle Instability (CAI). Unknown status NCT01733433
17 The Influence of Psychobiological Adversity to Children and Adolescents With Type 1 Diabetes Completed NCT02575001
18 Computer-assisted Instruction Before Colonoscopy is as Effective as Nurse Counselling, a Controlled Trial (PAVO-E-EDUC) Completed NCT02656602
19 Balance Training vs. Balance Training w/ STARS Completed NCT01790581
20 Cross Education Effect of Balance Program in Patients With Ankle Instability Completed NCT04072965
21 Androgen Receptor, Implications for Health and Wellbeing: Natural History Study of Individuals With Androgen Insensitivity Recruiting NCT04708431
22 Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence Recruiting NCT03423017
23 Growing up With the Young Endocrine Support System (YESS!): Innovative E-technology to Improve Transition From Paediatric to Adult Care Not yet recruiting NCT04252001
24 Balance Training With Transcranial Direct Current Stimulation (tDCS) for Chronic Ankle Instability (CAI) Not yet recruiting NCT04390048
25 A Multicenter, Randomized, Pivotal Study to Evaluate the Safety and Efficacy of the Cartilage Autograft Implantation System (CAIS) for the Surgical Treatment of Articular Cartilage Lesions of the Knee Terminated NCT00881023
26 A Clinical Trial for the Assessment of the Safety and Performance of the Vimecon Laser Cardiac Ablation Instrument (CAI) for the Interventional Treatment of Paroxysmal Atrial Fibrillation (AF) Terminated NCT02770989
27 Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity Terminated NCT01473732 Everolimus;Tacrolimus;Mycophenolic acid

Search NIH Clinical Center for Androgen Insensitivity Syndrome

Genetic Tests for Androgen Insensitivity Syndrome

Genetic tests related to Androgen Insensitivity Syndrome:

# Genetic test Affiliating Genes
1 Androgen Resistance Syndrome 29 AR

Anatomical Context for Androgen Insensitivity Syndrome

MalaCards organs/tissues related to Androgen Insensitivity Syndrome:

40
Testes, Uterus, Prostate, Bone, Skin, Brain, Testis

Publications for Androgen Insensitivity Syndrome

Articles related to Androgen Insensitivity Syndrome:

(show top 50) (show all 1197)
# Title Authors PMID Year
1
Genotype versus phenotype in families with androgen insensitivity syndrome. 6 57 25 61 54
11549642 2001
2
Postnatal changes of T, LH, and FSH in 46,XY infants with mutations in the AR gene. 54 57 6 25
11788616 2002
3
Androgen insensitivity with mental retardation: a contiguous gene syndrome? 54 25 57 61
9039995 1997
4
Clinical and biochemical investigations and molecular analysis of subjects with mutations in the androgen receptor gene. 54 25 6 61
9039340 1996
5
The androgen receptor gene mutations database: 2012 update. 25 61 6
22334387 2012
6
Residual activity of mutant androgen receptors explains wolffian duct development in the complete androgen insensitivity syndrome. 6 25 61
15531547 2004
7
Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome. 61 6 25
9360511 1997
8
Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. 6 25 61
9007482 1997
9
Probing the functional link between androgen receptor coactivator and ligand-binding sites in prostate cancer and androgen insensitivity. 54 61 6
16365032 2006
10
Complete androgen insensitivity syndrome caused by a novel mutation in the ligand-binding domain of the androgen receptor: functional characterization. 61 54 6
12213902 2002
11
Two de novo mutations in the AR gene cause the complete androgen insensitivity syndrome in a pair of monozygotic twins. 6 54 61
11889162 2002
12
Male fertility is compatible with an Arg(840)Cys substitution in the AR in a large Chinese family affected with divergent phenotypes of AR insensitivity syndrome. 61 54 6
11788673 2002
13
A novel E153X point mutation in the androgen receptor gene in a patient with complete androgen insensitivity syndrome. 61 54 6
11225909 1999
14
Point mutations in the steroid-binding domain of the androgen receptor gene of five Japanese patients with androgen insensitivity syndrome. 54 6 61
10458483 1999
15
Trafficking of androgen receptor mutants fused to green fluorescent protein: a new investigation of partial androgen insensitivity syndrome. 6 61 54
9768671 1998
16
Inherited and de novo androgen receptor gene mutations: investigation of single-case families. 6 25
9627582 1998
17
Wide variation in androgen receptor dysfunction in complete androgen insensitivity syndrome. 61 54 6
9328206 1997
18
Androgen insensitivity syndrome due to new mutations in the DNA-binding domain of the androgen receptor. 6 54 61
8809734 1996
19
Characterization of mutant androgen receptors causing partial androgen insensitivity syndrome. 6 54 61
8126121 1994
20
A single amino acid substitution (gly743 --> val) in the steroid-binding domain of the human androgen receptor leads to Reifenstein syndrome. 6 61 54
8325932 1993
21
Identification of two additional novel mutations in the AR gene associated with severe forms of androgen insensitivity syndrome. 61 6
31499074 2019
22
Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy. 61 6
30599484 2018
23
Phenotypic and molecular characteristics of androgen insensitivity syndrome patients. 6 61
29785970 2018
24
Mutational analysis of the androgen receptor (NR3C4) gene in patients with 46,XY DSD. 6 61
29051026 2018
25
Clinical and molecular characteristics in 15 patients with androgen receptor gene mutations from South China. 61 6
28261839 2017
26
AR mutations in 28 patients with androgen insensitivity syndrome (Prader grade 0-3). 6 61
28624954 2017
27
[Analysis of AR gene mutation in a family affected with complete androgen insensitivity syndrome using long chain RT-PCR]. 61 6
28186600 2017
28
Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with Partial Androgen Insensitivity Syndrome in an Individual with 47,XXY Karyotype. 61 6
28456808 2017
29
Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity. 6 61
27583472 2016
30
Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer. 61 6
27267075 2016
31
Clinical, cytogenetic and molecular analysis of androgen insensitivity syndromes from south Indian cohort and detection and in-silico characterization of androgen receptor gene mutations. 6 61
26688387 2016
32
Androgen insensitivity syndrome in a cohort of Sri Lankan children with 46, XY disorders of sex development (46, XY DSD). 61 6
26778393 2015
33
Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia. 6 61
25433660 2015
34
Different types of androgen receptor mutations in patients with complete androgen insensitivity syndrome. 6 61
25674389 2015
35
Characteristic features of reproductive hormone profiles in late adolescent and adult females with complete androgen insensitivity syndrome. 61 6
25613104 2015
36
Mutation analysis of androgen receptor gene: multiple uses for a single test. 61 6
25241384 2014
37
Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology. 61 6
24186138 2014
38
Genetic diagnosis and genetic counseling for androgen-insensitivity syndrome: a report of three cases. 6 61
24321103 2014
39
Promoter-dependent activity on androgen receptor N-terminal domain mutations in androgen insensitivity syndrome. 61 6
25500996 2014
40
C601S mutation in the androgen receptor results in partial loss of androgen function. 61 6
20493947 2010
41
Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations. 61 6
19463997 2010
42
Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development. 61 6
20150575 2010
43
Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine. 6 61
20011049 2009
44
Apolipoprotein D (APOD) is a putative biomarker of androgen receptor function in androgen insensitivity syndrome. 61 54 25
19330472 2009
45
Prenatal diagnosis of androgen insensitivity syndrome. 25 61 54
19844078 2009
46
Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. 25 54 61
17970778 2008
47
A novel mutation of androgen receptor gene in complete androgen insensitivity syndrome. 6 61
24790346 2007
48
Glutamic acid 709 substitutions highlight the importance of the interaction between androgen receptor helices H3 and H12 for androgen and antiandrogen actions. 61 6
16373394 2006
49
Molecular features and clinical phenotypes in androgen insensitivity syndrome in the absence and presence of androgen receptor gene mutations. 6 61
16283146 2005
50
Dissecting phenotypic variation among AIS patients. 61 6
16083860 2005

Variations for Androgen Insensitivity Syndrome

ClinVar genetic disease variations for Androgen Insensitivity Syndrome:

6 (show top 50) (show all 193)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AR AR, PARTIAL DEL Deletion Pathogenic 9802 GRCh37:
GRCh38:
2 AR AR, PARTIAL DEL Deletion Pathogenic 9803 GRCh37:
GRCh38:
3 AR NM_000044.6(AR):c.2323C>T (p.Arg775Cys) SNV Pathogenic 9804 rs137852562 GRCh37: X:66941679-66941679
GRCh38: X:67721837-67721837
4 AR NM_000044.6(AR):c.2157G>A (p.Trp719Ter) SNV Pathogenic 9805 rs137852563 GRCh37: X:66931515-66931515
GRCh38: X:67711673-67711673
5 AR NM_000044.6(AR):c.2599G>A (p.Val867Met) SNV Pathogenic 9806 rs137852564 GRCh37: X:66942818-66942818
GRCh38: X:67722976-67722976
6 AR NM_000044.6(AR):c.2391G>A (p.Trp797Ter) SNV Pathogenic 9807 rs137852565 GRCh37: X:66941747-66941747
GRCh38: X:67721905-67721905
7 AR NM_000044.6(AR):c.1771A>T (p.Lys591Ter) SNV Pathogenic 9808 rs137852566 GRCh37: X:66905854-66905854
GRCh38: X:67686012-67686012
8 AR NM_000044.6(AR):c.2650A>T (p.Lys884Ter) SNV Pathogenic 9811 rs137852568 GRCh37: X:66943570-66943570
GRCh38: X:67723728-67723728
9 AR NM_000044.6(AR):c.2362A>G (p.Met788Val) SNV Pathogenic 9814 rs137852570 GRCh37: X:66941718-66941718
GRCh38: X:67721876-67721876
10 LOC109504725 , AR NM_000044.6(AR):c.180_181del (p.Gln61fs) Deletion Pathogenic 9815 rs869320731 GRCh37: X:66765168-66765169
GRCh38: X:67545326-67545327
11 AR NM_000044.6(AR):c.2571C>G (p.Phe857Leu) SNV Pathogenic 9816 rs137852598 GRCh37: X:66942790-66942790
GRCh38: X:67722948-67722948
12 AR NM_000044.6(AR):c.2324G>A (p.Arg775His) SNV Pathogenic 9819 rs137852572 GRCh37: X:66941680-66941680
GRCh38: X:67721838-67721838
13 LOC109504725 , AR NM_000044.6(AR):c.178C>T (p.Gln60Ter) SNV Pathogenic 9825 rs137852575 GRCh37: X:66765166-66765166
GRCh38: X:67545324-67545324
14 AR NM_000044.3(AR):c.(2173+1_2174-1)_(2318+1_2319-1)del Deletion Pathogenic 9826 GRCh37:
GRCh38:
15 AR NM_000044.3(AR):c.(2318+1_2319-1)_(2607+1_2608-1)del Deletion Pathogenic 9827 GRCh37:
GRCh38:
16 AR NM_000044.6(AR):c.2033T>C (p.Leu678Pro) SNV Pathogenic 9832 rs137852579 GRCh37: X:66931391-66931391
GRCh38: X:67711549-67711549
17 AR NM_000044.6(AR):c.2123T>G (p.Leu708Arg) SNV Pathogenic 9837 rs137852585 GRCh37: X:66931481-66931481
GRCh38: X:67711639-67711639
18 AR NM_000044.6(AR):c.1739G>T (p.Cys580Phe) SNV Pathogenic 9838 rs137852586 GRCh37: X:66863220-66863220
GRCh38: X:67643378-67643378
19 AR NM_000044.6(AR):c.1748T>A (p.Phe583Tyr) SNV Pathogenic 9839 rs137852587 GRCh37: X:66863229-66863229
GRCh38: X:67643387-67643387
20 AR NM_000044.6(AR):c.2343G>T (p.Met781Ile) SNV Pathogenic 9842 rs137852589 GRCh37: X:66941699-66941699
GRCh38: X:67721857-67721857
21 LOC109504725 , AR NM_000044.6(AR):c.179dup (p.Gln61fs) Duplication Pathogenic 9848 rs759327087 GRCh37: X:66765166-66765167
GRCh38: X:67545324-67545325
22 AR NM_000044.6(AR):c.2667C>T (p.Ser889=) SNV Pathogenic 9850 rs137852594 GRCh37: X:66943587-66943587
GRCh38: X:67723745-67723745
23 AR NM_000044.6(AR):c.2137C>T (p.Leu713Phe) SNV Pathogenic 9852 rs137852595 GRCh37: X:66931495-66931495
GRCh38: X:67711653-67711653
24 AR NM_000044.6(AR):c.1732G>A (p.Gly578Arg) SNV Pathogenic 9853 rs137852596 GRCh37: X:66863213-66863213
GRCh38: X:67643371-67643371
25 AR NM_000044.6(AR):c.2596T>C (p.Ser866Pro) SNV Pathogenic 9854 rs137852597 GRCh37: X:66942815-66942815
GRCh38: X:67722973-67722973
26 AR NM_000044.6(AR):c.2521C>T (p.Arg841Cys) SNV Pathogenic 9830 rs137852577 GRCh37: X:66942740-66942740
GRCh38: X:67722898-67722898
27 AR NM_000044.6(AR):c.2069A>C (p.His690Pro) SNV Pathogenic 9856 rs137852599 GRCh37: X:66931427-66931427
GRCh38: X:67711585-67711585
28 AR NM_000044.6(AR):c.2231G>T (p.Gly744Val) SNV Pathogenic 9857 rs137852600 GRCh37: X:66937377-66937377
GRCh38: X:67717535-67717535
29 AR NM_000044.6(AR):c.2231G>A (p.Gly744Glu) SNV Pathogenic 9858 rs137852600 GRCh37: X:66937377-66937377
GRCh38: X:67717535-67717535
30 AR NM_000044.6(AR):c.2281_2287delinsTTCGCCCCTGA (p.Arg761fs) Indel Pathogenic 9859 rs869320732 GRCh37: X:66937427-66937433
GRCh38: X:67717585-67717591
31 AR NM_000044.6(AR):c.865G>T (p.Glu289Ter) SNV Pathogenic 373921 rs750324117 GRCh37: X:66765853-66765853
GRCh38: X:67546011-67546011
32 AR NM_000044.6(AR):c.1846C>T (p.Arg616Cys) SNV Pathogenic 434266 rs1555990485 GRCh37: X:66905929-66905929
GRCh38: X:67686087-67686087
33 LOC109504725 , AR NM_000044.6(AR):c.172CAG[(38_?)] (p.Gln80_Glu81insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) Microsatellite Pathogenic 155759 GRCh37: X:66765160-66765162
GRCh38: X:67545318-67545320
34 AR NM_000044.6(AR):c.2495G>A (p.Arg832Gln) SNV Pathogenic 458366 rs1386577803 GRCh37: X:66942714-66942714
GRCh38: X:67722872-67722872
35 AR NM_000044.6(AR):c.292C>T (p.Gln98Ter) SNV Pathogenic 464802 rs1555969553 GRCh37: X:66765280-66765280
GRCh38: X:67545438-67545438
36 AR NM_000044.6(AR):c.1847G>A (p.Arg616His) SNV Pathogenic 279684 rs754201976 GRCh37: X:66905930-66905930
GRCh38: X:67686088-67686088
37 AR NM_000044.6(AR):c.2359C>T (p.Arg787Ter) SNV Pathogenic 458364 rs1555997580 GRCh37: X:66941715-66941715
GRCh38: X:67721873-67721873
38 AR NM_000044.6(AR):c.2176T>C (p.Phe726Leu) SNV Pathogenic 458362 rs1555996810 GRCh37: X:66937322-66937322
GRCh38: X:67717480-67717480
39 AR NC_000023.11:g.(?_67686010)_(67686126_?)del Deletion Pathogenic 464783 GRCh37: X:66905852-66905968
GRCh38: X:67686010-67686126
40 AR NM_000044.6(AR):c.1440dup (p.Tyr481fs) Duplication Pathogenic 464787 rs1555970004 GRCh37: X:66766423-66766424
GRCh38: X:67546581-67546582
41 AR NM_000044.6(AR):c.1443C>G (p.Tyr481Ter) SNV Pathogenic 458358 rs766161615 GRCh37: X:66766431-66766431
GRCh38: X:67546589-67546589
42 AR NM_000044.6(AR):c.2296G>A (p.Ala766Thr) SNV Pathogenic 458363 rs1555996863 GRCh37: X:66937442-66937442
GRCh38: X:67717600-67717600
43 AR NM_000044.6(AR):c.749dup (p.Val251fs) Duplication Pathogenic 464803 rs1555969684 GRCh37: X:66765734-66765735
GRCh38: X:67545892-67545893
44 AR NM_000044.6(AR):c.321C>A (p.Tyr107Ter) SNV Pathogenic 458367 rs1481151440 GRCh37: X:66765309-66765309
GRCh38: X:67545467-67545467
45 LOC109504725 , AR NM_000044.6(AR):c.268C>T (p.Gln90Ter) SNV Pathogenic 458365 rs1555969545 GRCh37: X:66765256-66765256
GRCh38: X:67545414-67545414
46 AR NM_000044.6(AR):c.2086G>A (p.Asp696Asn) SNV Pathogenic 492787 rs1555995840 GRCh37: X:66931444-66931444
GRCh38: X:67711602-67711602
47 AR NM_000044.6(AR):c.2155T>C (p.Trp719Arg) SNV Pathogenic 492790 rs1555995865 GRCh37: X:66931513-66931513
GRCh38: X:67711671-67711671
48 LOC109504725 , AR NM_000044.6(AR):c.217C>T (p.Gln73Ter) SNV Pathogenic 492776 rs1199988820 GRCh37: X:66765205-66765205
GRCh38: X:67545363-67545363
49 AR NM_000044.6(AR):c.475G>A (p.Ala159Thr) SNV Pathogenic 492777 rs370215797 GRCh37: X:66765463-66765463
GRCh38: X:67545621-67545621
50 AR NM_000044.6(AR):c.2437C>T (p.Leu813Phe) SNV Pathogenic 492797 rs1555997625 GRCh37: X:66941793-66941793
GRCh38: X:67721951-67721951

UniProtKB/Swiss-Prot genetic disease variations for Androgen Insensitivity Syndrome:

72 (show top 50) (show all 109)
# Symbol AA change Variation ID SNP ID
1 AR p.Ile665Asn VAR_004687
2 AR p.Leu678Pro VAR_004688 rs137852579
3 AR p.Asp696His VAR_004690
4 AR p.Asp696Asn VAR_004691 rs155599584
5 AR p.Asp696Val VAR_004692
6 AR p.Ser704Gly VAR_004693
7 AR p.Leu708Arg VAR_004694 rs137852585
8 AR p.Asp733Asn VAR_004696
9 AR p.Asp733Tyr VAR_004697
10 AR p.Gly744Val VAR_004699 rs137852600
11 AR p.Met750Val VAR_004700 rs108530768
12 AR p.Gly751Asp VAR_004701
13 AR p.Arg753Gln VAR_004702 rs105752374
14 AR p.Phe755Val VAR_004703
15 AR p.Leu763Phe VAR_004704
16 AR p.Ala766Thr VAR_004707 rs155599686
17 AR p.Arg775His VAR_004708 rs137852572
18 AR p.Arg775Cys VAR_004709 rs137852562
19 AR p.Arg780Trp VAR_004710
20 AR p.Met781Ile VAR_004711 rs137852589
21 AR p.Cys785Tyr VAR_004712
22 AR p.Met788Val VAR_004713 rs137852570
23 AR p.Phe795Ser VAR_004714
24 AR p.Gln799Glu VAR_004715 rs137852591
25 AR p.Met808Arg VAR_004716
26 AR p.Met808Val VAR_004717
27 AR p.Ser815Asn VAR_004718
28 AR p.Arg832Leu VAR_004719
29 AR p.Arg832Gln VAR_004720 rs138657780
30 AR p.Arg841Cys VAR_004721 rs137852577
31 AR p.Arg841His VAR_004723 rs9332969
32 AR p.Ile843Thr VAR_004724 rs9332970
33 AR p.Arg856Cys VAR_004725 rs886041132
34 AR p.Arg856His VAR_004726 rs9332971
35 AR p.Asp865Asn VAR_004727 rs155599781
36 AR p.Val867Glu VAR_004728
37 AR p.Val867Met VAR_004730 rs137852564
38 AR p.Pro893Leu VAR_004733
39 AR p.Met896Thr VAR_004734
40 AR p.Leu908Phe VAR_004735
41 AR p.Gln196Arg VAR_009224
42 AR p.Leu257Pro VAR_009225
43 AR p.Pro392Arg VAR_009226 rs773996740
44 AR p.Pro392Ser VAR_009227 rs201934623
45 AR p.Gly492Ser VAR_009719
46 AR p.Pro549Ser VAR_009722 rs137852588
47 AR p.Cys560Tyr VAR_009723
48 AR p.Tyr572Cys VAR_009727
49 AR p.Ala574Asp VAR_009728
50 AR p.Cys577Phe VAR_009731

Expression for Androgen Insensitivity Syndrome

Search GEO for disease gene expression data for Androgen Insensitivity Syndrome.

Pathways for Androgen Insensitivity Syndrome

Pathways related to Androgen Insensitivity Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.58 SRD5A2 SRD5A1 NCOA2 AR
2
Show member pathways
11.39 NR5A1 NR1H2 AR
3
Show member pathways
11.23 SRD5A2 SRD5A1 CGA
4 10.58 SHBG AR
5 10.5 SRY NCOA2 AR

GO Terms for Androgen Insensitivity Syndrome

Cellular components related to Androgen Insensitivity Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.61 SHBG S100A6 PTGDS MUC5AC MUC1 INS
2 Golgi lumen GO:0005796 8.92 MUC5AC MUC1 INS CGA

Biological processes related to Androgen Insensitivity Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.09 SRY NR5A1 NR1H2 NCOA2 INS IGF2
2 lipid metabolic process GO:0006629 9.93 SRD5A2 SRD5A1 PTGDS NR1H2 APOD
3 positive regulation of gene expression GO:0010628 9.89 SRY NR5A1 NR1H2 INS AR
4 positive regulation of transcription by RNA polymerase II GO:0045944 9.8 SRY NR5A1 NR1H2 NCOA2 IGF2 CGA
5 positive regulation of MAPK cascade GO:0043410 9.75 INS IGF2 AR
6 male genitalia development GO:0030539 9.57 SRD5A2 SRD5A1
7 androgen metabolic process GO:0008209 9.56 SRD5A2 SRD5A1
8 positive regulation of glycogen biosynthetic process GO:0045725 9.52 INS IGF2
9 positive regulation of cellular protein metabolic process GO:0032270 9.51 NR1H2 INS
10 glucose metabolic process GO:0006006 9.5 INS IGF2 APOD
11 male sex determination GO:0030238 9.48 SRY NR5A1
12 androgen biosynthetic process GO:0006702 9.46 SRD5A2 SRD5A1
13 positive regulation of male gonad development GO:2000020 9.43 SRY NR5A1
14 cellular response to testosterone stimulus GO:0071394 9.4 SRD5A1 AR
15 sex determination GO:0007530 9.37 SRD5A1 NR5A1
16 intracellular receptor signaling pathway GO:0030522 9.33 NR5A1 NR1H2 AR
17 sex differentiation GO:0007548 9.13 SRY SRD5A2 SRD5A1
18 male gonad development GO:0008584 9.02 SRD5A2 SRD5A1 NR5A1 MAMLD1 AR

Molecular functions related to Androgen Insensitivity Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 9.71 SHBG NR5A1 AR APOD
2 hormone activity GO:0005179 9.54 INS IGF2 CGA
3 nuclear receptor activity GO:0004879 9.43 NR5A1 NR1H2 AR
4 insulin-like growth factor receptor binding GO:0005159 9.32 INS IGF2
5 3-oxo-5-alpha-steroid 4-dehydrogenase activity GO:0003865 9.16 SRD5A2 SRD5A1
6 cholestenone 5-alpha-reductase activity GO:0047751 8.96 SRD5A2 SRD5A1
7 androgen binding GO:0005497 8.8 SHBG AR ALDH1A1

Sources for Androgen Insensitivity Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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