46,XY sex reversal 5

Summary

46,XY sex reversal 5 (MONDO:0013120) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	46,XY sex reversal 5
Mondo ID	MONDO:0013120
MeSH	C567766
OMIM	613080
DOID	DOID:0111776
UMLS	C2751317
MedGen	414349
GARD	0015611
Is cancer (heuristic)	no

Also known as: 46,XY sex reversal 5 · 46,XY Sex reversal type 5 · 46XY sex reversal 5 · SRXY5

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › 46,XY complete gonadal dysgenesis › 46,XY sex reversal 5

Related subtypes (11): 46,XY sex reversal 4, 46,XY sex reversal 7, 46,XY sex reversal 2, 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, 46,XY sex reversal 3, 46,XY sex reversal 6, 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency, 46,XY sex reversal 9, 46,XY sex reversal 10, 46,XY sex reversal 1, 46,XY sex reversal 11

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
6826	NM_005189.3(CBX2):c.293C>T (p.Pro98Leu)	CBX2	Pathogenic	no assertion criteria provided
6827	NM_005189.3(CBX2):c.1328G>C (p.Arg443Pro)	CBX2	Pathogenic	no assertion criteria provided
3065334	NM_005189.3(CBX2):c.117-18del	CBX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3583088	NM_005189.3(CBX2):c.166C>T (p.Leu56=)	CBX2	Uncertain significance	criteria provided, single submitter
375260	NM_005189.3(CBX2):c.264del (p.Cys89fs)	CBX2	Uncertain significance	criteria provided, single submitter
3065910	NM_005189.3(CBX2):c.332C>T (p.Ser111Phe)	CBX2	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
CBX2	Limited	Semidominant	46,XY sex reversal 5	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CBX2	Orphanet:242	46,XY complete gonadal dysgenesis

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
CBX2	HGNC:1552	ENSG00000173894	Q14781	Chromobox protein homolog 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CBX2	Chromobox protein homolog 2	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CBX2	Other/Unknown	no		Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromodomain_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
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CBX2	178	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CBX2	1,609

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CBX2	Q14781	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
SUMOylation of DNA methylation proteins	1	671.8×	0.013	CBX2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.013	CBX2
SUMOylation of transcription cofactors	1	243.0×	0.013	CBX2
SUMOylation of RNA binding proteins	1	237.9×	0.013	CBX2
PTEN Regulation	1	228.4×	0.013	CBX2
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.013	CBX2
Regulation of PTEN gene transcription	1	178.4×	0.013	CBX2
SUMOylation	1	163.1×	0.013	CBX2
SUMOylation of chromatin organization proteins	1	158.6×	0.013	CBX2
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.013	CBX2
Transcriptional regulation by RUNX1	1	146.4×	0.013	CBX2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.013	CBX2
Cellular Senescence	1	137.6×	0.013	CBX2
Intracellular signaling by second messengers	1	91.4×	0.018	CBX2
Oxidative Stress Induced Senescence	1	90.6×	0.018	CBX2
PIP3 activates AKT signaling	1	66.8×	0.022	CBX2
Cellular responses to stress	1	36.8×	0.038	CBX2
Cellular responses to stimuli	1	31.5×	0.042	CBX2
RNA Polymerase II Transcription	1	22.5×	0.056	CBX2
Post-translational protein modification	1	19.2×	0.063	CBX2
Gene expression (Transcription)	1	17.8×	0.064	CBX2
Generic Transcription Pathway	1	15.1×	0.072	CBX2
Metabolism of proteins	1	12.4×	0.084	CBX2
Signal Transduction	1	10.2×	0.098	CBX2

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
development of primary sexual characteristics	1	16852.0×	2e-04	CBX2
cell differentiation	1	29.1×	0.052	CBX2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	CBX2

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
CBX2	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
CBX2	12	Binding:11, Functional:1

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	CBX2

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)
CBX2	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.