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POF7
MCID: PRM093
MIFTS: 47

Premature Ovarian Failure 7 (POF7)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Rare diseases, Reproductive diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Premature Ovarian Failure 7

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MalaCards integrated aliases for Premature Ovarian Failure 7:

Name: Premature Ovarian Failure 7 57 72 29 13 6 70
Adrenocortical Insufficiency 57 6 17
Adrenal Insufficiency, Nr5a1-Related 72 6
Pof7 57 72
Adrenal Insufficiency, Nr5a1 Related 36
Ovarian Failure, Premature, Type 7 39
Adrenal Cortical Hypofunction 70
Hypoaldosteronism 70
Ainr 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
familial cases may have affected 46,xy family members who exhibit sex reversal (see srxy3, )


HPO:

31
premature ovarian failure 7:
Inheritance sex-limited autosomal dominant


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Reproductive diseases Endocrine diseases Bone diseases
See all MalaCards categories (disease lists)


External Ids:

OMIM® 57 612964
OMIM Phenotypic Series 57 PS311360
KEGG 36 H02316
UMLS 70 C0020595 C0405580 C2751825
Sources

Summaries for Premature Ovarian Failure 7

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UniProtKB/Swiss-Prot : 72 Adrenal insufficiency, NR5A1-related: A disorder characterized by adrenal insufficiency, muscular hypotonia, decreased sodium and increased potassium levels, elevated ACTH, salt- wasting crisis, prolonged jaundice, hypoglycemia, and vomiting.
Premature ovarian failure 7: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.

MalaCards based summary : Premature Ovarian Failure 7, also known as adrenocortical insufficiency, is related to hypoadrenocorticism, familial and adrenoleukodystrophy. An important gene associated with Premature Ovarian Failure 7 is NR5A1 (Nuclear Receptor Subfamily 5 Group A Member 1), and among its related pathways/superpathways is Cortisol synthesis and secretion. The drugs Hydrocortisone and Hydrocortisone acetate have been mentioned in the context of this disorder. Affiliated tissues include pituitary, cortex and adrenal cortex, and related phenotypes are premature ovarian insufficiency and primary amenorrhea

KEGG : 36 NR5A1, also termed steroidogenic factor 1 (SF-1), is a nuclear receptor and a key transcriptional regulator of genes involved in the hypothalamic-pituitary-steroidogenic axis. There are some known mutations of the NR5A1 gene in humans. A few of them were originally identified in patients with adrenal insufficiency. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency.

More information from OMIM: 612964 PS311360
Sources

Related Diseases for Premature Ovarian Failure 7

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Diseases in the Premature Ovarian Failure 2a family:

Premature Ovarian Failure 2b Premature Ovarian Failure 1
Premature Ovarian Failure 3 Premature Ovarian Failure 5
Premature Ovarian Failure 6 Premature Ovarian Failure 10
Premature Ovarian Failure 7 Premature Ovarian Failure 8
Premature Ovarian Failure 9 Premature Ovarian Failure 11
Premature Ovarian Failure 12 Premature Ovarian Failure 13
Premature Ovarian Failure 14 Premature Ovarian Failure 15
Premature Ovarian Failure 16 Premature Ovarian Failure 17
Premature Ovarian Failure 18 Premature Ovarian Failure 19
Acquired Premature Ovarian Failure

Diseases related to Premature Ovarian Failure 7 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 161)
# Related Disease Score Top Affiliating Genes
1 hypoadrenocorticism, familial 31.6 NR5A1 ABCD1
2 adrenoleukodystrophy 11.5
3 acute adrenal insufficiency 11.2
4 lipoid congenital adrenal hyperplasia 11.1
5 achalasia-addisonianism-alacrima syndrome 10.5
6 familial glucocorticoid deficiency 10.5
7 primary adrenal insufficiency 10.3
8 achalasia 10.3
9 hypoglycemia 10.3
10 bilateral massive adrenal hemorrhage 10.3
11 dowling-degos disease 1 10.1
12 pulmonary tuberculosis 10.1
13 thyroiditis 10.1
14 hyperthyroidism 10.1
15 hypopituitarism 10.1
16 adrenomyeloneuropathy 10.1
17 adrenal hypoplasia, congenital, with absent pituitary luteinizing hormone 10.1
18 adrenal hypoplasia, congenital 10.1
19 familial hypoaldosteronism 10.1
20 rare hypoaldosteronism 10.1
21 inherited isolated adrenal insufficiency due to partial cyp11a1 deficiency 10.1
22 early-onset familial hypoaldosteronism 10.1
23 late-onset familial hypoaldosteronism 10.1
24 acth deficiency, isolated 10.1
25 myasthenia gravis 10.1
26 ocular motor apraxia 10.1
27 autosomal recessive disease 10.1
28 graves' disease 10.1
29 hypothyroidism 10.1
30 secondary adrenal insufficiency 10.1
31 adrenogenital syndrome 10.1
32 vitiligo-associated multiple autoimmune disease susceptibility 6 10.0
33 immune deficiency disease 10.0
34 graves disease 1 10.0
35 vitiligo-associated multiple autoimmune disease susceptibility 1 10.0
36 hyperprolactinemia 10.0
37 hypoparathyroidism 10.0
38 autonomic neuropathy 10.0
39 nephrotic syndrome 10.0
40 polyneuropathy 10.0
41 toxic shock syndrome 10.0
42 pituitary adenoma 10.0
43 liver disease 10.0
44 acquired immunodeficiency syndrome 10.0
45 amyloidosis 10.0
46 sheehan syndrome 10.0
47 growth hormone deficiency 10.0
48 encephalopathy 10.0
49 pfeiffer syndrome 9.8
50 autoimmune disease 9.8

Comorbidity relations with Premature Ovarian Failure 7 via Phenotypic Disease Network (PDN): (show all 15)


Active Peptic Ulcer Disease Acute Cystitis
Bronchitis Conn's Syndrome
Deficiency Anemia Esophagitis
Familial Atrial Fibrillation Heart Disease
Hypothyroidism Osteoporosis
Pituitary Hormone Deficiency, Combined, 2 Protein-Energy Malnutrition
Respiratory Failure Rheumatoid Arthritis
Temporal Arteritis

Graphical network of the top 20 diseases related to Premature Ovarian Failure 7:



Diseases related to Premature Ovarian Failure 7
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Symptoms & Phenotypes for Premature Ovarian Failure 7

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Human phenotypes related to Premature Ovarian Failure 7:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 premature ovarian insufficiency 31 very rare (1%) HP:0008209
2 primary amenorrhea 31 very rare (1%) HP:0000786
3 secondary amenorrhea 31 very rare (1%) HP:0000869
4 absent pubic hair 31 very rare (1%) HP:0002555
5 hypoplasia of the uterus 31 very rare (1%) HP:0000013
6 clitoral hypertrophy 31 very rare (1%) HP:0008665
7 elevated circulating follicle stimulating hormone level 31 very rare (1%) HP:0008232
8 elevated circulating luteinizing hormone level 31 very rare (1%) HP:0011969
9 gonadal dysgenesis 31 HP:0000133

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary Internal Genitalia Female:
secondary amenorrhea
irregular menstrual cycles
primary amenorrhea (in some patients)
anovulatory menstrual cycles
primary ovarian insufficiency
more
Chest Breasts:
absent thelarche (in some patients)
small breasts (in some patients)

Skin Nails Hair Hair:
absent pubic hair (in some patients)

Endocrine Features:
low estradiol
elevated luteinizing hormone (lh)
elevated follicle-stimulating hormone (fsh)

Genitourinary External Genitalia Female:
hypertrophic clitoris (in some patients)

Clinical features from OMIM®:

612964 (Updated 20-May-2021)

Sources

Drugs & Therapeutics for Premature Ovarian Failure 7

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Drugs for Premature Ovarian Failure 7 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 28)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydrocortisone Approved, Vet_approved Phase 2, Phase 3 50-23-7 5754
2
Hydrocortisone acetate Approved, Vet_approved Phase 2, Phase 3 50-03-3
3 Pharmaceutical Solutions Phase 2, Phase 3
4 Anti-Inflammatory Agents Phase 2, Phase 3
5 Hydrocortisone 17-butyrate 21-propionate Phase 2, Phase 3
6 Hydrocortisone hemisuccinate Phase 2, Phase 3
7
Fludrocortisone Approved, Investigational Phase 2 127-31-1 31378
8
Fentanyl Approved, Illicit, Investigational, Vet_approved 437-38-7 3345
9
Midazolam Approved, Illicit 59467-70-8 4192
10
Etomidate Approved 33125-97-2 36339 667484
11
Succinylcholine Approved 306-40-1 5314
12
Epinephrine Approved, Vet_approved 51-43-4 5816
13
Racepinephrine Approved 329-65-7 838
14 Hypnotics and Sedatives
15 Psychotropic Drugs
16 Narcotics
17 Anesthetics
18 Neurotransmitter Agents
19 Neuromuscular Blocking Agents
20 Anesthetics, Intravenous
21 Anesthetics, General
22 GABA Modulators
23 Anti-Anxiety Agents
24 Analgesics, Opioid
25 Analgesics
26 Mineralocorticoids
27 Estrogens
28 Epinephryl borate

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Interest of Treatment of Polytraumatisms With Corticoids (Hydrocortisone) for Patient With Relative Adrenocortical Insufficiency Completed NCT00563303 Phase 2, Phase 3 hydrocortisone;NaCl
2 Impact of the Administration of Fludrocortisone on Fluid and Electrolyte Balance in Very Premature Infants: Pilot Study Completed NCT03001089 Phase 2 Oral Fludrocortisone (enteral);Placebo Oral Tablet
3 A Single Dose of Etomidate During Rapid Sequence Induction in Trauma Patients Causes Significant Adrenocortical Insufficiency: A Prospective Randomized Study Completed NCT00462644 RSI sedation with etomidate/succinylcholine;RSI sedation with fentanyl/midazolam/succinylcholine
4 Prospective Evaluation of Adrenal Function After Living Donor Nephrectomy With or Without Ligation of the Adrenal Vein Completed NCT00251836
5 Ovarian Follicle Function in Patients With Primary Ovarian Insufficiency Completed NCT00001275
6 Optimization of the Evaluation of the Adrenal Function After Discontinuation of a Prolonged Therapy With Corticosteroids Terminated NCT01053754
7 Investigation of Gene Polymorphisms Influencing Steroid Synthesis and Action in Patients With Deficient Steroid Biosynthesis and Disorders of Sex Development Withdrawn NCT00485186

Search NIH Clinical Center for Premature Ovarian Failure 7

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Genetic Tests for Premature Ovarian Failure 7

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Genetic tests related to Premature Ovarian Failure 7:

# Genetic test Affiliating Genes
1 Premature Ovarian Failure 7 29 NR5A1
Sources

Anatomical Context for Premature Ovarian Failure 7

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MalaCards organs/tissues related to Premature Ovarian Failure 7:

40
Pituitary, Cortex, Adrenal Cortex, Uterus, Skin, Adrenal Gland, Bone
Sources

Publications for Premature Ovarian Failure 7

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Articles related to Premature Ovarian Failure 7:

(show top 50) (show all 817)
# Title Authors PMID Year
1
Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. 61 57 6
11038323 2000
2
Rare Causes of Primary Adrenal Insufficiency: Genetic and Clinical Characterization of a Large Nationwide Cohort. 57 6
26523528 2016
3
Mutations in NR5A1 associated with ovarian insufficiency. 57 6
19246354 2009
4
Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. 57 6
11932325 2002
5
A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant. 6
27855412 2017
6
Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals. 57
28033660 2016
7
Screening and familial characterization of copy-number variations in NR5A1 in 46,XY disorders of sex development and premature ovarian failure. 57
23918653 2013
8
Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. 6
20887963 2010
9
Identification of mutations in the putative ATP-binding domain of the adrenoleukodystrophy gene. 6
8040304 1994
10
The Diagnosis and Management of Endocrine Side Effects of Immune Checkpoint Inhibitors. 61
33724917 2021
11
Clinical and endocrinological manifestations of childhood-onset craniopharyngioma before surgical removal: A report from one medical center in Taiwan. 61
33376065 2021
12
Venoarterial extracorporeal membrane oxygenation as bridge to effective treatment in a 19-year-old woman with acute adrenal crisis: a case report. 61
33644667 2021
13
Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy in Two Siblings: Same Mutations but Very Different Phenotypes. 61
33530632 2021
14
Congenital Agenesis of the Olfactory Bulbs: What to Suspect? 61
33585143 2021
15
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency - The next disease included in the neonatal screening program in poland. 61
33742965 2021
16
Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature. 61
32851966 2021
17
Effects of dehydroepiandrosterone on quality of life in premenopausal women with rheumatoid arthritis: A preliminary randomized clinical trial. 61
32975909 2020
18
Pubertal development and premature ovarian insufficiency in patients with APECED. 61
33107435 2020
19
A novel variant in AIRE causing a rare, non‑classical autoimmune polyendocrine syndrome type 1. 61
32627016 2020
20
Spontaneous fertility and variable spectrum of reproductive phenotype in a family with adult-onset X-linked adrenal insufficiency harboring a novel DAX-1/NR0B1 mutation. 61
32028936 2020
21
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling. 61
32047678 2020
22
Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected. 61
32903448 2020
23
[Controlling glucocorticoid treatment in critically ill patients with rheumatism exemplified by systemic lupus erythematosus]. 61
31410548 2019
24
[A Case of Isolated ACTH Deficiency Induced by Nivolumab in a Patient with Gastric Cancer Metastasis of the Peritoneum]. 61
31879407 2019
25
Novel mutation in AIRE gene with autoimmune polyendocrine syndrome type 1. 61
31526676 2019
26
A novel ABCD1 gene mutation causes adrenomyeloneuropathy in a Chinese family. 61
31557422 2019
27
Clinical characteristics and phenotype distribution in 10 Chinese patients with X-linked adrenoleukodystrophy. 61
31452695 2019
28
Chinese patients with adrenoleukodystrophy and Zellweger spectrum disorder presenting with hereditary spastic paraplegia. 61
31227335 2019
29
[A case of secondary adrenocortical insufficiency due to isolated ACTH deficiency that developed following a mental health disorder]. 61
30867341 2019
30
[Clinical and mutational analysis of 7 children with X-linked adrenal dysplasia congenita]. 61
31055805 2019
31
Adrenal insufficiency of patients with graft versus host disease treated with extracorporeal photopheresis. 61
31188658 2019
32
Falsely elevated plasma ACTH levels measured by the Elecsys assay related to heterophilic antibody in a case of secondary adrenocortical insufficiency. 61
30944263 2019
33
Late adult-onset adrenomyeloneuropathy evolving with atypical severe frontal lobe syndrome: Importance of neuroimaging. 61
30546814 2019
34
Bilateral Adrenocortical Adenomas along with Virilization and Cushing's Syndrome. 61
30210105 2019
35
Limbal stem cell defficiency associated with primary adrenocortical insufficiency. 61
30828512 2019
36
The potential role for infections in the pathogenesis of autoimmune Addison's disease. 61
30144040 2019
37
Broadening the Spectrum of Adulthood X-Linked Adrenoleukodystrophy: A Report of Two Atypical Cases. 61
30787906 2019
38
Increased risk of autoimmune diseases in dengue patients: A population-based cohort study. 61
29746944 2018
39
Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors. 61
28859919 2018
40
Evaluation of Hypothalamic-Pituitary-Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test. 61
30324179 2018
41
[The 464th case: sudden convulsion and coma in a patient with acute leukemia]. 61
29996279 2018
42
Atypical Presentation of Adrenocortical Insufficiency with Anorexia and Jaundice. 61
29910458 2018
43
Psychiatric disease in an adolescent as a harbinger of cerebral X-linked adrenoleukodystrophy. 61
29175874 2018
44
Rapid whole-genome sequencing identifies a novel AIRE variant associated with autoimmune polyendocrine syndrome type 1. 61
29437776 2018
45
The natural history of autoimmune Addison's disease with a non-classical presentation: a case report and review of literature. 61
29478039 2018
46
Low-dose Synachten test with measurement of salivary cortisol in adult patients with β-thalassemia major. 61
29572711 2018
47
[The Waterhouse-Friderichsen syndrome]. 61
30040272 2018
48
Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma. 61
29475919 2018
49
ATP7B Mutation Detection and Pathogenicity Analysis: One Atypical Case of Wilson's Disease with Adrenocortical Insufficiency. 61
29181760 2018
50
Treatment of Addison's disease during pregnancy. 61
29675257 2018
Sources

Variations for Premature Ovarian Failure 7

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ClinVar genetic disease variations for Premature Ovarian Failure 7:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NR5A1 NM_004959.5(NR5A1):c.764G>T (p.Arg255Leu) SNV Pathogenic 12795 rs104894118 GRCh37: 9:127262475-127262475
GRCh38: 9:124500196-124500196
2 NR5A1 NM_004959.5(NR5A1):c.275G>A (p.Arg92Gln) SNV Pathogenic 12796 rs104894119 GRCh37: 9:127262964-127262964
GRCh38: 9:124500685-124500685
3 ABCD1 NM_000033.4(ABCD1):c.1817C>T (p.Ser606Leu) SNV Pathogenic 11310 rs128624225 GRCh37: X:153008477-153008477
GRCh38: X:153743023-153743023
4 ABCD1 ABCD1, 1-BP DEL, 2204G Deletion Pathogenic 11311 GRCh37:
GRCh38:
5 NR5A1 NM_004959.5(NR5A1):c.368G>C (p.Gly123Ala) SNV Pathogenic 12809 rs200163795 GRCh37: 9:127262871-127262871
GRCh38: 9:124500592-124500592
6 NR5A1 NM_004959.5(NR5A1):c.682_690CTGCAGCTG[1] (p.228_230LQL[1]) Microsatellite Pathogenic 12808 rs606231208 GRCh37: 9:127262540-127262548
GRCh38: 9:124500261-124500269
7 NR5A1 NM_004959.5(NR5A1):c.390del (p.Pro131fs) Deletion Pathogenic 12807 rs606231207 GRCh37: 9:127262849-127262849
GRCh38: 9:124500570-124500570
8 NR5A1 NM_004959.5(NR5A1):c.3G>A (p.Met1Ile) SNV Pathogenic 12806 rs121918656 GRCh37: 9:127265672-127265672
GRCh38: 9:124503393-124503393
9 NR5A1 NM_004959.5(NR5A1):c.877G>A (p.Asp293Asn) SNV Pathogenic 12805 rs121918655 GRCh37: 9:127255422-127255422
GRCh38: 9:124493143-124493143
10 NR5A1 NM_004959.5(NR5A1):c.666del (p.Asn222fs) Deletion Pathogenic 12804 rs606231206 GRCh37: 9:127262573-127262573
GRCh38: 9:124500294-124500294

UniProtKB/Swiss-Prot genetic disease variations for Premature Ovarian Failure 7:

72
# Symbol AA change Variation ID SNP ID
1 NR5A1 p.Arg92Gln VAR_016982 rs104894119
2 NR5A1 p.Arg255Leu VAR_016983 rs104894118
3 NR5A1 p.Gly123Ala VAR_062967 rs200163795
4 NR5A1 p.Pro129Leu VAR_062968 rs200749741
5 NR5A1 p.Asp293Asn VAR_062970 rs121918655

Sources

Expression for Premature Ovarian Failure 7

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Search GEO for disease gene expression data for Premature Ovarian Failure 7.
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Pathways for Premature Ovarian Failure 7

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Pathways related to Premature Ovarian Failure 7 according to KEGG:

36
# Name Kegg Source Accession
1 Cortisol synthesis and secretion hsa04927
Sources

GO Terms for Premature Ovarian Failure 7

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Molecular functions related to Premature Ovarian Failure 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 enzyme binding GO:0019899 8.62 NR5A1 ABCD1
Sources

Sources for Premature Ovarian Failure 7

About this section
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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