46,XX sex reversal 2

Summary

46,XX sex reversal 2 (MONDO:0010218) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	46,XX sex reversal 2
Mondo ID	MONDO:0010218
OMIM	278850
DOID	DOID:0111763
UMLS	C2749215
MedGen	411414
GARD	0015249
Is cancer (heuristic)	no

Also known as: 46,XX sex reversal 2 · 46,XX Sex reversal type 2 · 46XX sex reversal 2 · SRXX2

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › disorder of sexual differentiation › 46,XX disorder of sex development › 46,XX testicular disorder of sex development › 46,XX sex reversal 2

Related subtypes (3): 46,XX sex reversal 3, 46,XX sex reversal 4, 46,XX sex reversal 1

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

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
192386	NCBI36/hg18 17q24.3(chr17:67018227-67114737)x3	SOX9	Pathogenic	no assertion criteria provided
192387	NC_000017.10:g.69521863_69670036dup	SOX9	Pathogenic	no assertion criteria provided
30708	NC_000017.10:g.(69320000_69330000)_(69527000_69517000)dup	SOX9	Pathogenic	no assertion criteria provided
599355	GRCh37/hg19 17q24.3(chr17:69458883-69482850)x3	SOX9	Pathogenic	criteria provided, single submitter
599356	GRCh37/hg19 17q24.3(chr17:69475275-69499520)x3	SOX9	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence

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
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf

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
cranial nerve II	1
hair follicle	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOX9	4,935

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOX9	P48436	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Transcriptional regulation of testis differentiation	1	713.8×	0.010	SOX9
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.010	SOX9
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.010	SOX9
Transcriptional regulation by RUNX2	1	253.8×	0.010	SOX9
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.010	SOX9
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.010	SOX9
Developmental Cell Lineages	1	223.9×	0.010	SOX9
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.011	SOX9
TCF dependent signaling in response to WNT	1	117.7×	0.013	SOX9
MITF-M-regulated melanocyte development	1	114.2×	0.013	SOX9
Signaling by WNT	1	112.0×	0.013	SOX9
RNA Polymerase II Transcription	1	22.5×	0.059	SOX9
Gene expression (Transcription)	1	17.8×	0.069	SOX9
Generic Transcription Pathway	1	15.1×	0.074	SOX9
Developmental Biology	1	14.5×	0.074	SOX9
Signal Transduction	1	10.2×	0.098	SOX9

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
negative regulation of immune system process	1	8426.0×	0.001	SOX9
epithelial cell proliferation involved in prostatic bud elongation	1	8426.0×	0.001	SOX9
regulation of cell proliferation involved in tissue homeostasis	1	8426.0×	0.001	SOX9
regulation of branching involved in lung morphogenesis	1	8426.0×	0.001	SOX9
cell proliferation involved in heart morphogenesis	1	8426.0×	0.001	SOX9
regulation of epithelial cell proliferation involved in lung morphogenesis	1	8426.0×	0.001	SOX9
heart valve formation	1	5617.3×	0.001	SOX9
neural crest cell fate specification	1	5617.3×	0.001	SOX9
male germ-line sex determination	1	5617.3×	0.001	SOX9
intrahepatic bile duct development	1	5617.3×	0.001	SOX9
bronchus cartilage development	1	5617.3×	0.001	SOX9
lung smooth muscle development	1	5617.3×	0.001	SOX9
ureter urothelium development	1	5617.3×	0.001	SOX9
ureter smooth muscle cell differentiation	1	5617.3×	0.001	SOX9
negative regulation of beta-catenin-TCF complex assembly	1	5617.3×	0.001	SOX9
glial cell fate specification	1	4213.0×	0.001	SOX9
cellular response to heparin	1	4213.0×	0.001	SOX9
renal vesicle induction	1	4213.0×	0.001	SOX9
positive regulation of kidney development	1	4213.0×	0.001	SOX9
chondrocyte hypertrophy	1	3370.4×	0.001	SOX9
growth plate cartilage chondrocyte growth	1	3370.4×	0.001	SOX9
astrocyte fate commitment	1	3370.4×	0.001	SOX9
trachea cartilage development	1	3370.4×	0.001	SOX9
morphogenesis of a branching epithelium	1	3370.4×	0.001	SOX9
Harderian gland development	1	3370.4×	0.001	SOX9
metanephric nephron tubule formation	1	3370.4×	0.001	SOX9
positive regulation of cell proliferation involved in heart morphogenesis	1	3370.4×	0.001	SOX9
chondrocyte differentiation involved in endochondral bone morphogenesis	1	2808.7×	0.002	SOX9
anterior head development	1	2808.7×	0.002	SOX9
negative regulation of photoreceptor cell differentiation	1	2407.4×	0.002	SOX9

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SOX9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SOX9	3	Binding:3

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	SOX9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SOX9	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.