Cryptorchidism

Summary

Cryptorchidism (MONDO:0009047) is a disease with 14 cohort genes and 31 clinical trials. Top therapeutic interventions include bupivacaine, gonadorelin acetate, and propofol.

At a glance

• Cohort genes: 14
• ClinVar variants: 28
• Clinical trials: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cryptorchidism
Mondo ID	MONDO:0009047
EFO	EFO:0004562
MeSH	D003456
OMIM	219050
DOID	DOID:11383
ICD-11	1134950387
NCIT	C12326
SNOMED CT	204878001
UMLS	C0010417
MedGen	8192
Is cancer (heuristic)	no

Also known as: cryptorchidism · cryptorchidism (disease) · undescended testes · undescended testicle · undescended testis

Data availability: 28 ClinVar variants · 3 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › cryptorchidism

Related subtypes (25): benign male reproductive system neoplasm, hematocele of tunica vaginalis testis, male genital organ stricture, male genital organ vascular disease, penile disorder, testicular disorder, prostate disorder, epididymitis, hydrocele, male infertility, male genital tuberculosis, spermatocele, dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome, diphallia, postorgasmic illness syndrome, penoscrotal transposition, congenital bilateral absence of vas deferens, posterior hypospadias, isolated micropenis, male reproductive system neoplasm, fournier gangrene, congenital agenesis of the scrotum, scrotal disorder, congenital megaprepuce, epididymis disease

Subtypes (1): Arroyo Garcia Cimadevilla syndrome

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

28 retrieved; paginated sample, class counts are floors:

14 pathogenic, 6 uncertain significance, 3 conflicting classifications of pathogenicity, 2 benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267833	46;XY;t(6;12)(q14;q24);20p+dn		Pathogenic	criteria provided, single submitter
267853	46;XY;inv(10)(q11.2q24)dn		Pathogenic	criteria provided, single submitter
267937	46;XY;t(5;15)(q11.2;q24)		Pathogenic	criteria provided, single submitter
268006	46;XY;t(6;11)(p12.3;p14.2)dn		Pathogenic	criteria provided, single submitter
242882	NM_013275.6(ANKRD11):c.5317G>T (p.Glu1773Ter)	ANKRD11	Pathogenic	no assertion criteria provided
373906	NM_001370658.1(BTD):c.40_41del (p.Gly14fs)	BTD	Pathogenic	criteria provided, single submitter
997057	GRCh37/hg19 22q11.21(chr22:18909044-21464119)	GGTLC3	Pathogenic	criteria provided, single submitter
14829	NM_005543.4(INSL3):c.330C>G (p.Asn110Lys)	INSL3	Pathogenic	no assertion criteria provided
14830	NM_005543.4(INSL3):c.278C>T (p.Pro93Leu)	INSL3	Pathogenic	no assertion criteria provided
14831	NM_005543.4(INSL3):c.304C>T (p.Arg102Cys)	INSL3	Pathogenic	no assertion criteria provided
37092	NM_005543.4(INSL3):c.217C>T (p.Arg73Ter)	INSL3	Pathogenic	no assertion criteria provided
684729	NM_032793.5(MFSD2A):c.229-25_229-23del	MFSD2A	Pathogenic	no assertion criteria provided
1047897	GRCh37/hg19 9q34.3(chr9:139284464-141018984)	MIR126	Pathogenic	criteria provided, single submitter
996741	NM_012233.3(RAB3GAP1):c.151-5T>G	RAB3GAP1	Pathogenic	no assertion criteria provided
208490	NM_006009.4(TUBA1A):c.1226T>C (p.Val409Ala)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4279048	NM_005543.4(INSL3):c.176_182del (p.Ala59fs)	INSL3	Likely pathogenic	criteria provided, single submitter
374171	NM_133433.4(NIPBL):c.1811_1812del (p.Lys603_Ser604insTer)	NIPBL	Likely pathogenic	criteria provided, single submitter
14832	NM_005543.4(INSL3):c.305G>A (p.Arg102His)	INSL3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523500	NM_012330.4(KAT6B):c.5213C>T (p.Thr1738Ile)	KAT6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4159	NM_130806.5(RXFP2):c.664A>C (p.Thr222Pro)	RXFP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267808	46;XY;t(4;14)(p15.32;q32.1)dn		Uncertain significance	criteria provided, single submitter
267820	46;XY;t(16;20)(q11.2;q13.2)dn		Uncertain significance	criteria provided, single submitter
523303	GRCh37/hg19 6q25.3(chr6:156772218-157870875)x3	ARID1B	Uncertain significance	criteria provided, single submitter
1806185	NM_005543.4(INSL3):c.191G>T (p.Arg64Leu)	INSL3	Uncertain significance	criteria provided, multiple submitters, no conflicts
623485	NM_014462.3(LSM1):c.231+4A>C	LSM1	Uncertain significance	criteria provided, multiple submitters, no conflicts
431465	NM_015295.3(SMCHD1):c.511T>G (p.Phe171Val)	SMCHD1	Uncertain significance	criteria provided, single submitter
1253265	NM_005543.4(INSL3):c.178A>G (p.Thr60Ala)	INSL3	Benign	criteria provided, multiple submitters, no conflicts
1271020	NM_005543.4(INSL3):c.126A>G (p.Leu42=)	INSL3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 18 · 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
INSL3	Moderate	Autosomal dominant	cryptorchidism	2
RXFP2	Limited	Autosomal recessive	cryptorchidism	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BTD	Orphanet:79241	Biotinidase deficiency
RAB3GAP1	Orphanet:1387	Cataract-intellectual disability-hypogonadism syndrome
RAB3GAP1	Orphanet:2510	Micro syndrome
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
ARID1B	Orphanet:1465	Coffin-Siris syndrome
ARID1B	Orphanet:251056	6q25.2q25.3 microdeletion syndrome
TUBA1A	Orphanet:171680	Lissencephaly due to TUBA1A mutation
TUBA1A	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBA1A	Orphanet:467166	Tubulinopathy-associated dysgyria
TUBA1A	Orphanet:994	Fetal akinesia deformation sequence
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
MFSD2A	Orphanet:2512	Autosomal recessive primary microcephaly
NIPBL	Orphanet:199	Cornelia de Lange syndrome
NIPBL	Orphanet:329802	5p13 microduplication syndrome
SMCHD1	Orphanet:2250	Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome
SMCHD1	Orphanet:269	Facioscapulohumeral dystrophy

Cohort genes → proteins

14 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RXFP2	HGNC:17318	ENSG00000133105	Q8WXD0	Relaxin receptor 2	gencc,clinvar
INSL3	HGNC:6086	ENSG00000248099	P51460	Insulin-like 3	gencc,clinvar
BTD	HGNC:1122	ENSG00000169814	P43251	Biotinidase	clinvar
RAB3GAP1	HGNC:17063	ENSG00000115839	Q15042	Rab3 GTPase-activating protein catalytic subunit	clinvar
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
ARID1B	HGNC:18040	ENSG00000049618	Q8NFD5	AT-rich interactive domain-containing protein 1B	clinvar
LSM1	HGNC:20472	ENSG00000175324	O15116	U6 snRNA-associated Sm-like protein LSm1	clinvar
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	clinvar
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
MFSD2A	HGNC:25897	ENSG00000168389	Q8NA29	Sodium-dependent lysophosphatidylcholine symporter 1	clinvar
NIPBL	HGNC:28862	ENSG00000164190	Q6KC79	Nipped-B-like protein	clinvar
SMCHD1	HGNC:29090	ENSG00000101596	A6NHR9	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	clinvar
MIR126	HGNC:31508	ENSG00000199161		microRNA 126	clinvar
GGTLC3	HGNC:33426	ENSG00000274252	B5MD39	Glutathione hydrolase light chain 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RXFP2	Relaxin receptor 2	Receptor for relaxin.
INSL3	Insulin-like 3	Seems to play a role in testicular function.
BTD	Biotinidase	Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.
RAB3GAP1	Rab3 GTPase-activating protein catalytic subunit	Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins.
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
ARID1B	AT-rich interactive domain-containing protein 1B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
LSM1	U6 snRNA-associated Sm-like protein LSm1	Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated.
TUBA1A	Tubulin alpha-1A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
MFSD2A	Sodium-dependent lysophosphatidylcholine symporter 1	Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.
NIPBL	Nipped-B-like protein	Plays an important role in the loading of the cohesin complex on to DNA.
SMCHD1	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture.
GGTLC3	Glutathione hydrolase light chain 3	Likely to be catalytically inactive.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 8 · Druggable fraction: 0.29

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
Transporter	1	5.6×	0.799
Protease	1	2.6×	0.799
GPCR	1	1.7×	0.799
Scaffold/PPI	1	1.2×	0.799
Other/Unknown	8	1.0×	0.799
Enzyme (other)	1	0.9×	0.822
Transcription factor	1	0.6×	0.836

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RXFP2	GPCR	yes		GPCR_Rhodpsn, Leu-rich_rpt, LDrepeatLR_classA_rpt
INSL3	Other/Unknown	no		Insulin-like, Insulin_CS, Insulin-like_sf
BTD	Enzyme (other)	yes	3.5.1.12	C-N_Hydrolase, Biotinidase-like_euk, C-N_Hydrolase_sf
RAB3GAP1	Other/Unknown	no		Rab3GAP1_conserved, Rab3GAP1_C, Rab3GAP1
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
ARID1B	Other/Unknown	no		ARID_dom, BAF250/Osa, BAF250_C
LSM1	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm1
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
MFSD2A	Transporter	yes		MFS_trans_sf, MFS_2
NIPBL	Other/Unknown	no		ARM-like, ARM-type_fold, Nipped-B_C
SMCHD1	Other/Unknown	no		SMC_hinge, SMC_hinge_sf, HATPase_C_sf
MIR126	Other/Unknown	no
GGTLC3	Protease	yes		GGT_peptidase, Ntn_hydrolases_N, GGT_ssub_C

Expression context

Cohort genes with no expression data: 0.

10 cohort genes 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
sural nerve	3
colonic epithelium	3
right lobe of liver	2
hair follicle	2
cortical plate	2
calcaneal tendon	2
buccal mucosa cell	1
monocyte	1
adult organism	1
left testis	1
right testis	1
islet of Langerhans	1
liver	1
Brodmann (1909) area 23	1
secondary oocyte	1
ventricular zone	1
bone marrow cell	1
gingival epithelium	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RXFP2	61	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, monocyte
INSL3	158	tissue_specific	marker	adult organism, right testis, left testis
BTD	261	ubiquitous	marker	islet of Langerhans, right lobe of liver, liver
RAB3GAP1	300	ubiquitous	marker	hair follicle, Brodmann (1909) area 23, secondary oocyte
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
ARID1B	256	ubiquitous	marker	bone marrow cell, colonic epithelium, sural nerve
LSM1	296	ubiquitous	marker	parotid gland, gingival epithelium, hair follicle
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
MFSD2A	220	ubiquitous	marker	right lobe of liver, skin of abdomen, ileal mucosa
NIPBL	288	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, colonic epithelium
SMCHD1	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, blood
MIR126	109		yes	placenta, renal glomerulus, skeletal muscle tissue
GGTLC3	99		yes	male germ line stem cell (sensu Vertebrata) in testis, right lobe of thyroid gland, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NIPBL	3,278
ANKRD11	2,384
KAT6B	2,214
ARID1B	2,131
LSM1	2,060
RAB3GAP1	2,039
SMCHD1	1,888
RXFP2	1,538
TUBA1A	1,436
BTD	1,311

Intra-cohort edges

A	B	Sources
ANKRD11	ARID1B	string_interaction
ANKRD11	NIPBL	string_interaction
INSL3	RXFP2	biogrid_interaction, string_interaction

Structural data

PDB: 9 · AlphaFold-only: 4 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBA1A	Q71U36	15
INSL3	P51460	3
KAT6B	Q8WYB5	3
NIPBL	Q6KC79	3
ARID1B	Q8NFD5	2
RXFP2	Q8WXD0	1
RAB3GAP1	Q15042	1
MFSD2A	Q8NA29	1
SMCHD1	A6NHR9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GGTLC3	B5MD39	92.84
LSM1	O15116	89.59
BTD	P43251	86.77
ANKRD11	Q6UB99	39.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 131. Enrichment computed across 14 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Relaxin receptors	2	253.8×	0.003	RXFP2, INSL3
Defective BTD causes biotidinase deficiency	1	1142.0×	0.044	BTD
COPI-independent Golgi-to-ER retrograde traffic	2	41.5×	0.044	RAB3GAP1, TUBA1A
Defects in biotin (Btn) metabolism	1	228.4×	0.109	BTD
Cohesin Loading onto Chromatin	1	114.2×	0.109	NIPBL
Biotin transport and metabolism	1	103.8×	0.109	BTD
Chromatin organization	2	16.3×	0.109	KAT6B, ARID1B
Class A/1 (Rhodopsin-like receptors)	2	14.8×	0.109	RXFP2, INSL3
Peptide ligand-binding receptors	2	14.8×	0.109	RXFP2, INSL3
G alpha (s) signalling events	2	14.6×	0.109	RXFP2, INSL3
Chromatin modifying enzymes	2	14.5×	0.109	KAT6B, ARID1B
GPCR ligand binding	2	12.8×	0.109	RXFP2, INSL3
Deadenylation-dependent mRNA decay	1	87.8×	0.114	LSM1
mRNA decay by 5’ to 3’ exoribonuclease	1	76.1×	0.117	LSM1
Formation of the canonical BAF (cBAF) complex	1	63.4×	0.117	ARID1B
Defects in vitamin and cofactor metabolism	1	60.1×	0.117	BTD
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	54.4×	0.117	TUBA1A
Transport of connexons to the plasma membrane	1	54.4×	0.117	TUBA1A
Gap junction trafficking and regulation	1	47.6×	0.117	TUBA1A
Gap junction trafficking	1	47.6×	0.117	TUBA1A
Post-chaperonin tubulin folding pathway	1	47.6×	0.117	TUBA1A
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	45.7×	0.117	ARID1B
Formation of tubulin folding intermediates by CCT/TriC	1	42.3×	0.117	TUBA1A
Synthesis of PC	1	40.8×	0.117	MFSD2A
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	40.8×	0.117	TUBA1A
Prefoldin mediated transfer of substrate to CCT/TriC	1	39.4×	0.117	TUBA1A
Activation of AMPK downstream of NMDARs	1	38.1×	0.117	TUBA1A
Regulation of endogenous retroelements	1	36.8×	0.117	ARID1B
RHO GTPases activate IQGAPs	1	34.6×	0.117	TUBA1A
Sealing of the nuclear envelope (NE) by ESCRT-III	1	34.6×	0.117	TUBA1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
face morphogenesis	3	114.4×	3e-04	RAB3GAP1, ANKRD11, NIPBL
external genitalia morphogenesis	1	1296.3×	0.018	NIPBL
lysophospholipid translocation	1	1296.3×	0.018	MFSD2A
regulation of phosphatidylethanolamine metabolic process	1	1296.3×	0.018	MFSD2A
obsolete regulation of phosphatidylserine metabolic process	1	1296.3×	0.018	MFSD2A
motor behavior	2	86.4×	0.018	TUBA1A, MFSD2A
brain development	3	18.3×	0.018	RAB3GAP1, MFSD2A, NIPBL
regulation of developmental growth	1	648.1×	0.018	NIPBL
gallbladder development	1	648.1×	0.018	NIPBL
positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization	1	648.1×	0.018	RAB3GAP1
regulation of phosphatidylcholine metabolic process	1	648.1×	0.018	MFSD2A
regulation of calcium ion-dependent exocytosis of neurotransmitter	1	648.1×	0.018	RAB3GAP1
cognition	2	43.9×	0.018	MFSD2A, NIPBL
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	2	33.7×	0.018	RXFP2, INSL3
establishment of protein localization to endoplasmic reticulum membrane	1	432.1×	0.022	RAB3GAP1
biotin metabolic process	1	324.1×	0.022	BTD
carbohydrate transport	1	324.1×	0.022	MFSD2A
negative regulation of fatty acid beta-oxidation	1	324.1×	0.022	MFSD2A
maintenance of mitotic sister chromatid cohesion	1	324.1×	0.022	NIPBL
ear morphogenesis	1	324.1×	0.022	NIPBL
eye morphogenesis	1	324.1×	0.022	NIPBL
positive regulation of protein lipidation	1	324.1×	0.022	RAB3GAP1
positive regulation of endoplasmic reticulum tubular network organization	1	324.1×	0.022	RAB3GAP1
pyramidal neuron differentiation	1	259.3×	0.024	TUBA1A
lysophospholipid transport	1	259.3×	0.024	MFSD2A
lipid transport across blood-brain barrier	1	259.3×	0.024	MFSD2A
photoreceptor cell morphogenesis	1	216.1×	0.025	MFSD2A
cerebellar cortex morphogenesis	1	216.1×	0.025	TUBA1A
uterus morphogenesis	1	216.1×	0.025	NIPBL
regulation of neuron projection arborization	1	216.1×	0.025	MFSD2A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 12

Druggability breadth: 5 of 14 evidence-associated genes (36%) 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
TUBA1A	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBA1A	22	4
SMCHD1	1	2
RXFP2	0	0
INSL3	0	0
BTD	0	0
RAB3GAP1	0	0
KAT6B	0	0
ARID1B	0	0
LSM1	0	0
ANKRD11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBA1A
VINBLASTINE	4	TUBA1A
LEVOFLOXACIN ANHYDROUS	4	TUBA1A
DOCETAXEL	4	TUBA1A
NOSCAPINE	4	TUBA1A
VINBLASTINE SULFATE	4	TUBA1A
PACLITAXEL	4	TUBA1A
LEVOFLOXACIN	4	TUBA1A
VINORELBINE	4	TUBA1A
TIRBANIBULIN	4	TUBA1A
PODOFILOX	4	TUBA1A
VINCRISTINE	4	TUBA1A
DOCETAXEL ANHYDROUS	4	TUBA1A
PATUPILONE	3	TUBA1A
ABT-751	2	TUBA1A
MAYTANSINE	2	TUBA1A
DOLASTATIN-10	2	TUBA1A
INDIBULIN	2	TUBA1A
PARBENDAZOLE	2	TUBA1A
NOCODAZOLE	2	TUBA1A
MOLIBRESIB	2	SMCHD1, TUBA1A
COMBRETASTATIN	1	TUBA1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
KAT6B	22	Binding:20, Functional:2
SMCHD1	7	Binding:7
RXFP2	5	Functional:3, Binding:2
BTD	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BTD	3.5.1.12	biotinidase
KAT6B	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TUBA1A	1,696

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

22 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)
COLCHICINE	4	TUBA1A
VINBLASTINE	4	TUBA1A
LEVOFLOXACIN ANHYDROUS	4	TUBA1A
DOCETAXEL	4	TUBA1A
NOSCAPINE	4	TUBA1A
VINBLASTINE SULFATE	4	TUBA1A
PACLITAXEL	4	TUBA1A
LEVOFLOXACIN	4	TUBA1A
VINORELBINE	4	TUBA1A
TIRBANIBULIN	4	TUBA1A
PODOFILOX	4	TUBA1A
VINCRISTINE	4	TUBA1A
DOCETAXEL ANHYDROUS	4	TUBA1A
PATUPILONE	3	TUBA1A
ABT-751	2	TUBA1A
MAYTANSINE	2	TUBA1A
DOLASTATIN-10	2	TUBA1A
INDIBULIN	2	TUBA1A
PARBENDAZOLE	2	TUBA1A
NOCODAZOLE	2	TUBA1A
MOLIBRESIB	2	SMCHD1, TUBA1A
COMBRETASTATIN	1	TUBA1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBA1A
B	Phased (≥1) drug, not yet approved	1	SMCHD1
C	Druggable family + PDB, no drug	2	RXFP2, MFSD2A
D	Druggable family + AlphaFold only, no drug	2	BTD, GGTLC3
E	Difficult family or no structure, no drug	8	INSL3, RAB3GAP1, KAT6B, ARID1B, LSM1, ANKRD11, NIPBL, MIR126

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RXFP2	5	—
INSL3	0	—
BTD	3	—
RAB3GAP1	0	—
KAT6B	22	—
ARID1B	0	—
LSM1	0	—
ANKRD11	0	—
MFSD2A	0	—
NIPBL	0	—
MIR126	0	—
GGTLC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 31.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	28
PHASE4	1
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02110745	PHASE4	COMPLETED	The Effect of Induction Technique on Postoperative Pain and Agitation
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT01701778	PHASE2	COMPLETED	Caudal Versus Intravenous Dexmedetomidine for Supplementation of Caudal Analgesia in Children
NCT04342026	Not specified	RECRUITING	Role of the Environment and Endocrine Disruptors in Child Cryptorchidism
NCT05097820	Not specified	RECRUITING	Prospective Observational Study on SEBBIN Silicone Gel-filled Testicular Implants
NCT06558994	Not specified	RECRUITING	Transection Versus Ligation of Internal Spermatic Vessels in Laparoscopic Fowler-Stephens Orchidopexy
NCT06698081	Not specified	RECRUITING	The Effect of Using Multimedia During the Informed Consent Process on the Anxiety of Parents of Orchiopexy Patients
NCT06862258	Not specified	NOT_YET_RECRUITING	Shehata Technique in the Treatment of Intra-abdominal Testis
NCT07106502	Not specified	NOT_YET_RECRUITING	Learning to Palpate the Child’s Testicles Using Simulation
NCT07233265	Not specified	RECRUITING	Comparison of Single Incision Scrotal vs Standard Two Incision Inguinal Orchidopexy in Children Under 10 Years.
NCT07426796	Not specified	RECRUITING	Comparison of Posterior QLB and QIPB in Pediatric Undescended Testis Surgery.
NCT07586332	Not specified	ACTIVE_NOT_RECRUITING	INVESTIGATION OF THE GENETIC ETIOLOGY OF HERNIA SAC DEVELOPMENT IN MALE CHILDREN WITH UNDESCENDED TESTIS AND INGUINAL HERNIA
NCT00253253	Not specified	COMPLETED	Long-Term Outcome in Congenital Undescended Testis After Surgical Treatment by Orchidopexy
NCT00264121	Not specified	UNKNOWN	The Incidence of Congenital Undescended Testis Among Dutch Infants
NCT00435383	Not specified	COMPLETED	Comparing Oxygen Saturation in Post Anesthesia Care Unit After Different Methods of Pain Relief
NCT00565513	Not specified	COMPLETED	Cryptorchidism: Impact of in Utero Exposure to Xenobiotics With Hormonal Action
NCT01604915	Not specified	COMPLETED	Comparison of Dexamethasone Added to Ropivacaine and Ropivacaine Alone in Caudal Analgesia in Children Undergoing Orchiopexy
NCT01896076	Not specified	COMPLETED	The Caudal Space in Children: Ultrasound Evaluation
NCT02040389	Not specified	COMPLETED	Visual Guidelines and Tutoring in Pediatric Urological Surgery
NCT02249637	Not specified	COMPLETED	A Novel Technique of Circumcision Incision Orchidopexy
NCT02731989	Not specified	UNKNOWN	Comparison Between the Clinical Assessment of the Undescended Testis and Its’ Ultrasonographic Size
NCT02936024	Not specified	UNKNOWN	One Stage vs. Two Stage Gubernaculum Sparing Laparoscopic Orchidopexy (GSLO)
NCT03575377	Not specified	COMPLETED	Opioid Use, Storage, and Disposal Among Pediatric Patients After Surgery
NCT03677453	Not specified	COMPLETED	Interactive Perioperative Teaching Platform (IPTP)
NCT04528381	Not specified	UNKNOWN	Role of Laparoscopy in Management of Non-palpable Undescended Testis : Assuit University Experience
NCT05558748	Not specified	UNKNOWN	Comparison of USG-Guided Caudal Versus Ilioinguinal/Iliohypogastric Nerve Block for Pediatric Inguinal Surgeries
NCT06187844	Not specified	UNKNOWN	Value of Inguinal Exploration for Impalpable Testes
NCT06533306	Not specified	COMPLETED	Metachronous Acquired Contralateral Cryptorchidism in Patients With a History of Unilateral Cryptorchidism.
NCT06560086	Not specified	UNKNOWN	Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Macrophage Trem2
NCT07315737	Not specified	COMPLETED	Could miRNAs be Used as Markers for Distinguishing Undescended Testicles From Retractile Testicles
NCT07319637	Not specified	COMPLETED	Comparing Two Types of Surgery for Children With Undescended Testicles When the Hernia Sac Is Tied or Not

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BUPIVACAINE	4	1
GONADORELIN ACETATE	4	1
PROPOFOL	4	1