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Adrenal insufficiency v1.0 POR Gene migrated from ENSG00000127948 to ENSG00000127948 (gene set migration)
Adrenal insufficiency v0.68 C14orf80 Chirag Patel gene: C14orf80 was added
gene: C14orf80 was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: C14orf80 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C14orf80 were set to 39979680; 38252227; 30842647
Phenotypes for gene: C14orf80 were set to Syndromic disease, MONDO:0002254
Review for gene: C14orf80 was set to RED
Added comment: Adrenal insufficiency only reported in 2 male siblings from 1 non-consanguineous family with biallelic loss‑of‑function TEDC1 variants (c.104-5C>G and p.Ala263LeufsTer29). They also had prenatal‑onset severe growth impairment, primary microcephaly, primary hypogonadism, congenital glaucoma, craniosynostosis, tracheal stenosis and developmental delay. Functional studies demonstrate loss of TEDC1 protein, disrupted TEDC2 binding, cell‑cycle defects in patient lymphoblastoid cells, and recapitulation of growth and cranial phenotypes in a tedc1‑/‑ zebrafish model.

Total of 5 individuals from 3 families reported with biallelic loss‑of‑function TEDC1 variants, presenting with developmental delay and microcephaly.
Sources: Literature
Adrenal insufficiency v0.66 CPOX Chirag Patel gene: CPOX was added
gene: CPOX was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: CPOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPOX were set to 40857591; 40481674; 40296768
Phenotypes for gene: CPOX were set to harderoporphyria, MONDO:0030048
Review for gene: CPOX was set to GREEN
Added comment: ClinGen DEFINITIVE association (Jan 2023).

Childhood‑onset primary adrenal insufficiency reported in 5 individuals from 4 unrelated families with biallelic loss‑of‑function CPOX variants, with 3 individuals also having 46,XY DSD (PMID 40296768 and 40481674).
Sources: Literature
Adrenal insufficiency v0.65 GFER Chirag Patel gene: GFER was added
gene: GFER was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 26018198
Phenotypes for gene: GFER were set to Mitochondrial disease, MONDO:0044970
Review for gene: GFER was set to RED
Added comment: ClinGen DEFINITIVE association with disease (Sep'23).
Only 1 patient aged 19 years reported with infancy onset adrenal insufficiency.
Sources: Literature
Adrenal insufficiency v0.63 HSD17B4 Chirag Patel gene: HSD17B4 was added
gene: HSD17B4 was added to Adrenal insufficiency. Sources: Literature,ClinGen
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD17B4 were set to 40416444; 32904102; 32528852
Phenotypes for gene: HSD17B4 were set to d-bifunctional protein deficiency, MONDO:0009855
Review for gene: HSD17B4 was set to GREEN
Added comment: ClinGen DEFINITIVE association with disease (Apr 2020).

Adrenal insufficiency reported in 5 individuals from 3 unrelated families with D‑bifunctional protein deficiency due to biallelic loss‑of‑function HSD17B4 variants.
Sources: Literature, ClinGen
Adrenal insufficiency v0.59 IARS2 Chirag Patel gene: IARS2 was added
gene: IARS2 was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to 30419932
Phenotypes for gene: IARS2 were set to cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, MONDO:0014455
Review for gene: IARS2 was set to AMBER
Added comment: Established gene-disease association with cataract‑growth hormone deficiency‑sensory neuropathy‑sensorineural hearing loss‑skeletal dysplasia (CAGSSS) syndrome.

PMID 30419932 reports 2 unrelated individuals with the same homozygous missense variant in IARS2 gene (p.Pro909Ser) presenting with CAGSSS syndrome and central adrenal insufficiency.
Sources: Literature
Adrenal insufficiency v0.56 POR Chirag Patel Marked gene: POR as ready
Adrenal insufficiency v0.56 POR Chirag Patel Gene: por has been classified as Green List (High Evidence).
Adrenal insufficiency v0.54 POLE Chirag Patel gene: POLE was added
gene: POLE was added to Adrenal insufficiency. Sources: Literature
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to 30503519
Phenotypes for gene: POLE were set to IMAGE-I syndrome, MONDO:0032684
Review for gene: POLE was set to GREEN
Added comment: IMAGEI is an autosomal recessive disorder characterized by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency.
15 individuals from 12 families reported with a recurrent intronic variant (c.1686+32C-G, intron 15) found in combination with multiple other variants.
Sources: Literature
Adrenal insufficiency v0.11 Chirag Patel Copied gene POR from panel Congenital adrenal hyperplasia
Adrenal insufficiency v0.11 POR Chirag Patel gene: POR was added
gene: POR was added to Adrenal insufficiency. Sources: Expert Review Green,Victorian Clinical Genetics Services,Victorian Clinical Genetics Services
Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POR were set to 27068427
Phenotypes for gene: POR were set to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571