inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency

Summary

inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency (MONDO:0017337) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• Phenotypes (HPO): 52

Clinical features

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000033	Ambiguous genitalia, male	Very frequent (80-99%)
HP:0000037	Male pseudohermaphroditism	Very frequent (80-99%)
HP:0000127	Renal salt wasting	Very frequent (80-99%)
HP:0000144	Decreased fertility	Very frequent (80-99%)
HP:0000151	Aplasia of the uterus	Very frequent (80-99%)
HP:0000771	Gynecomastia	Very frequent (80-99%)
HP:0000823	Delayed puberty	Very frequent (80-99%)
HP:0000848	Increased circulating renin level	Very frequent (80-99%)
HP:0000939	Osteoporosis	Very frequent (80-99%)
HP:0001197	Abnormality of prenatal development or birth	Very frequent (80-99%)
HP:0001274	Agenesis of corpus callosum	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001941	Acidosis	Very frequent (80-99%)
HP:0001944	Dehydration	Very frequent (80-99%)
HP:0001998	Neonatal hypoglycemia	Very frequent (80-99%)
HP:0002013	Vomiting	Very frequent (80-99%)
HP:0002153	Hyperkalemia	Very frequent (80-99%)
HP:0002615	Hypotension	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0002902	Hyponatremia	Very frequent (80-99%)
HP:0003107	Abnormality of cholesterol metabolism	Very frequent (80-99%)
HP:0003154	Increased circulating ACTH level	Very frequent (80-99%)
HP:0004319	Decreased circulating aldosterone level	Very frequent (80-99%)
HP:0004349	Reduced bone mineral density	Very frequent (80-99%)
HP:0007440	Generalized hyperpigmentation	Very frequent (80-99%)
HP:0007574	Generalized bronze hyperpigmentation	Very frequent (80-99%)
HP:0008073	Low maternal serum estriol	Very frequent (80-99%)
HP:0008163	Decreased circulating cortisol level	Very frequent (80-99%)
HP:0008187	Absence of secondary sex characteristics	Very frequent (80-99%)
HP:0008207	Primary adrenal insufficiency	Very frequent (80-99%)
HP:0008730	Female external genitalia in individual with 46,XY karyotype	Very frequent (80-99%)
HP:0008734	Decreased testicular size	Very frequent (80-99%)
HP:0010789	Abnormality of the Leydig cells	Very frequent (80-99%)
HP:0011106	Hypovolemia	Very frequent (80-99%)
HP:0011749	Adrenocorticotropic hormone excess	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0012244	Abnormal sex determination	Very frequent (80-99%)
HP:0012245	Sex reversal	Very frequent (80-99%)
HP:0012598	Abnormal urine potassium concentration	Very frequent (80-99%)
HP:0012605	Hypernatriuria	Very frequent (80-99%)
HP:0030349	Decreased circulating androgen level	Very frequent (80-99%)
HP:0030369	Induced vaginal delivery	Very frequent (80-99%)
HP:0100779	Urogenital sinus anomaly	Very frequent (80-99%)
HP:0000835	Adrenal hypoplasia	Frequent (30-79%)
HP:0001622	Premature birth	Frequent (30-79%)
HP:0008232	Elevated circulating follicle stimulating hormone level	Frequent (30-79%)
HP:0011969	Elevated circulating luteinizing hormone level	Frequent (30-79%)
HP:0000142	Abnormality of the vagina	Occasional (5-29%)
HP:0008665	Clitoral hypertrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency
Mondo ID	MONDO:0017337
Orphanet	289548
SNOMED CT	764960005
UMLS	C4707238
MedGen	1643960
GARD	0021143
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › adrenal cortex disorder › adrenocortical insufficiency › primary adrenal insufficiency › chronic primary adrenal insufficiency › inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency

Related subtypes (7): adrenocortical hypofunction, chronic primary congenital, familial adrenal hypoplasia with absent pituitary luteinizing hormone, familial glucocorticoid deficiency, triple-A syndrome, X-linked adrenal hypoplasia congenita, congenital adrenal hyperplasia, autoimmune primary adrenal insufficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CYP11A1	Strong	Autosomal recessive	Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP11A1	Orphanet:168558	46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency
CYP11A1	Orphanet:289548	Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP11A1	HGNC:2590	ENSG00000140459	P05108	Cholesterol side-chain cleavage enzyme, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP11A1	Cholesterol side-chain cleavage enzyme, mitochondrial	A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP11A1	Enzyme (other)	yes	1.14.15.6	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP11A1	136	broad	marker	adrenal tissue, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP11A1	2,123

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP11A1	P05108	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP11A1 causes AICSR	1	2284.0×	0.001	CYP11A1
Pregnenolone biosynthesis	1	815.7×	0.002	CYP11A1
Endogenous sterols	1	393.8×	0.003	CYP11A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
steroid hormone biosynthetic process	1	16852.0×	5e-04	CYP11A1
cortisol metabolic process	1	2808.7×	0.001	CYP11A1
C21-steroid hormone biosynthetic process	1	1872.4×	0.001	CYP11A1
glucocorticoid biosynthetic process	1	1532.0×	0.001	CYP11A1
vitamin D metabolic process	1	1532.0×	0.001	CYP11A1
sterol metabolic process	1	842.6×	0.001	CYP11A1
cellular response to peptide hormone stimulus	1	842.6×	0.001	CYP11A1
cholesterol metabolic process	1	195.9×	0.005	CYP11A1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYP11A1	AMINOGLUTETHIMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP11A1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMINOGLUTETHIMIDE	4	CYP11A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYP11A1	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP11A1	1.14.15.6	cholesterol monooxygenase (side-chain-cleaving)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
AMINOGLUTETHIMIDE	4	CYP11A1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP11A1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.