INSL3

Summary

INSL3 (insulin like 3, HGNC:6086) is a protein-coding gene on chromosome 19p13.11, encoding Insulin-like 3 (P51460). Seems to play a role in testicular function.

This gene encodes a member of the insulin-like hormone superfamily. The encoded protein is mainly produced in gonadal tissues. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. This protein may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. Mutations in this gene may lead to cryptorchidism. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 3640 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cryptorchidism (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 261 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_005543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6086
Approved symbol	INSL3
Name	insulin like 3
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	RLF, MGC119818, MGC119819
Ensembl gene	ENSG00000248099
Ensembl biotype	protein_coding
OMIM	146738
Entrez	3640

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000317306, ENST00000379695, ENST00000598577

RefSeq mRNA: 2 — MANE Select: NM_005543 NM_001265587, NM_005543

CCDS: CCDS12365, CCDS58655

Canonical transcript exons

ENST00000317306 — 2 exons

Exon	Start	End
ENSE00003174348	17816512	17817059
ENSE00003190473	17821317	17821519

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 98.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3845 / max 2064.6160, expressed in 7 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179889	2.3322	6
179885	0.0156	2
179886	0.0143	3
179883	0.0077	2
179882	0.0064	2
208727	0.0043	2
179884	0.0039	3

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	98.03	gold quality
right testis	UBERON:0004534	96.68	gold quality
left testis	UBERON:0004533	96.53	gold quality
testis	UBERON:0000473	95.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.82	gold quality
granulocyte	CL:0000094	77.96	gold quality
buccal mucosa cell	CL:0002336	76.92	silver quality
blood	UBERON:0000178	76.06	gold quality
spleen	UBERON:0002106	68.83	gold quality
vermiform appendix	UBERON:0001154	68.52	gold quality
right ovary	UBERON:0002118	67.14	gold quality
lymph node	UBERON:0000029	66.92	gold quality
left ovary	UBERON:0002119	65.48	gold quality
ovary	UBERON:0000992	65.05	gold quality
caecum	UBERON:0001153	64.03	gold quality
tendon of biceps brachii	UBERON:0008188	63.96	gold quality
lower esophagus mucosa	UBERON:0035834	63.61	gold quality
skin of hip	UBERON:0001554	62.36	silver quality
upper leg skin	UBERON:0004262	61.78	silver quality
CA1 field of hippocampus	UBERON:0003881	61.77	gold quality
tibialis anterior	UBERON:0001385	61.51	silver quality
body of stomach	UBERON:0001161	60.78	gold quality
pancreatic ductal cell	CL:0002079	60.54	silver quality
vena cava	UBERON:0004087	59.49	gold quality
endometrium epithelium	UBERON:0004811	58.65	gold quality
right coronary artery	UBERON:0001625	58.32	gold quality
cerebellar vermis	UBERON:0004720	58.22	gold quality
mucosa of transverse colon	UBERON:0004991	57.77	gold quality
gluteal muscle	UBERON:0002000	57.62	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	34397.03
E-ANND-3	no	2.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR4A1, NR5A1, NR5A2, TCF3

miRNA regulators (miRDB)

16 targeting INSL3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-6735-3P	96.10	63.81	600
HSA-MIR-4781-5P	88.22	64.40	100

Literature-anchored findings (GeneRIF, showing 40)

• Functional analysis of the mouse counterpart. (PMID:10391220)
• A novel mutation in this protein is found in patients with cryptorchidism. (PMID:12601553)
• differentially expressed in hyperplastic and neoplastic thyrocytes, and in various thyroid diseases (PMID:12684664)
• the only clinical consequence of alterations of the INSL3-LGR8 system seems to be failure of the testis to normally descend in the scrotum during embryonic development, without affecting the spermatogenic and endocrine components of the testis itself (PMID:12970298)
• Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to LH in a manner similar to that of the LH-testosterone axis. (PMID:15579743)
• Although a common polymorphism was identified in the INSL3 gene, no mutations were observed. Lack of association between genetic factors necessary for correct testicular descent and anorchia. (PMID:15579790)
• LGR8 signal is activated by the relaxin-like factor (PMID:15708846)
• Even testosterone and INSL3 are both dependent on lutropin, thesse two Leydig cell hormones are regulated differently. (PMID:15755855)
• relaxin-like hormones appear to be present early during C-cell hyperplasia and potentially functional relaxin/INSL3 ligand-receptor systems are present in human medullary thyroid carcinoma tissues and cell lines (PMID:15956746)
• Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to the luteinizing hormone (PMID:15956751)
• Strongest INSL3 expression was detected in the basal epithelial cell compartment of the prostate epithelial cells, while weaker mRNA expression and immunoreactive production were observed in secretory epithelial cells. (PMID:16010410)
• INSL3 is not sensitive to gonadotropin stimulation in normal men, but declines markedly in response to gonadotropin deprivation. (PMID:16394084)
• Thus, the human INSL3 promoter constitutes a novel target for the orphan nuclear receptor Nur77. (PMID:16467267)
• Results showed a significant association of INSL3 gene mutations in men presenting one or more signs of testicular dysgenesis syndrome. (PMID:16687567)
• INSL3 was found to adopt a characteristic relaxin/insulin-like fold in solution but is a highly dynamic molecule. The four termini of this two-chain peptide are disordered, and additional conformational exchange is evident in the molecular core. (PMID:16867980)
• The data show that INSL3 is an independent measure of Leydig cell function (quality and number), which appears to be independent of acute control via the HPG axis. (PMID:17014531)
• The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of cryptorchidism. (PMID:17028442)
• INSL3 blood levels may be higher in men with persistent spermatogenesis during treatment with male hormonal contraceptives. (PMID:17314233)
• INSL3 could be considered a new circulating hormone related to LH-dependent ovarian hyperandrogenism, particularly in normal-weight polycystic ovary women (PMID:17356050)
• Mutations involving the insulin-like factor 3 gene may contribute to other anomalies of male genital development, such as micropenis. (PMID:17437853)
• predicted the complete INSL3/LGR8 primary binding site, including interactions between INSL3 His-B12 and LGR8 Trp-177, INSL3 Val-B19 and LGR8 Ile-179, and INSL3 Arg-B20 with LGR8 Asp-181 and Glu-229 (PMID:17473281)
• Higher blood levels may be indicative of ovarian cancer. (PMID:17549672)
• The common INSL3 G178A polymorphism was not statistically significantly associated with male infertility. (PMID:17559848)
• In boys, early postnatal INSL3 is markedly higher as compared with later childhood, presumably because it is stimulated by the transient postnatal LH peak (PMID:17666478)
• negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor (PMID:18063691)
• INSL3 concentration in human amniotic fluid is potentially predictive of fetal sex and pre-eclampsia, and presumably reflects the functioning of the fetal Leydig cell population. (PMID:18310050)
• study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis (PMID:18433302)
• INSL3 is clearly present in human male amniotic fluid in the second trimester, where abdominal testis translocation takes place. (PMID:18611973)
• There is a significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations. (PMID:19017913)
• Analogues of INSL3 with higher alpha-helicity had higher receptor binding affinity. (PMID:19067106)
• Via comparison of the solution structure of a fully active carboxy-terminal cross-linked RLF analogue with the native synthetic human RLF, it becomes clear that the cross-linked analogue largely retains the essential folding of the native protein. (PMID:19086273)
• High INSL3 is associated with testicular Leydig cell tumors. (PMID:19110449)
• This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment. (PMID:19226271)
• The role of INSL3 throughout human reproduction is discussed. [review] (PMID:19329805)
• The receptor-binding residues of RLF are in the B chain of the two-chain molecule and extend from the midregion of the central helix to the tryptophan in position B27 (PMID:19416166)
• Several missense mutations were described in both the INSL3 and RXFP2 genes and a novel V39G INSL3 mutation in a patient with cryptorchidism was identified (PMID:19416188)
• This study confirmed the association between INSL3 and RXFP2 gene mutations and human cryptorchidism. (PMID:19416190)
• Data provide the first evidence that the INSL3 peptide can promote early tumor cell invasiveness in human thyroid carcinoma cells by enhancing their metabolic activity and elastin-degrading potential. (PMID:19416220)
• An early impairment of the overall Leydig cell function is present in men with T2DM, manifesting as reduced INSL3, mainly related to visceral adiposity rather than to glycemic control. (PMID:19755411)
• INSL3 is a powerful and multifunctional promoter of tumor growth and angiogenesis in human thyroid cancer cell xenografts. INSL3 actions involve RXFP2 activation and the secretion of S100A4 and (pro-)cathepsin-L (PMID:19950223)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	insl3	ENSDARG00000035862
mus_musculus	Insl3	ENSMUSG00000079019
rattus_norvegicus		ENSRNOG00000072911

Protein

Protein identifiers

Insulin-like 3 — P51460 (reviewed: P51460)

Alternative names: Leydig insulin-like peptide, Relaxin-like factor

All UniProt accessions (2): P51460, M0QXQ3

UniProt curated annotations — full annotation on UniProt →

Function. Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor.

Subunit / interactions. Heterodimer of a B chain and an A chain linked by two disulfide bonds.

Subcellular location. Secreted.

Tissue specificity. Expressed in prenatal and postnatal Leydig cells. Found as well in the corpus luteum, trophoblast, fetal membranes and breast.

Disease relevance. Cryptorchidism (CRYPTO) [MIM:219050] One of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the insulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51460-1	1	yes
P51460-2	2

RefSeq proteins (2): NP_001252516, NP_005534* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016179	Insulin-like	Domain
IPR022353	Insulin_CS	Conserved_site
IPR036438	Insulin-like_sf	Homologous_superfamily
IPR043387	INSL3/INSL4	Family

Pfam: PF00049

UniProt features (20 total): sequence variant 8, helix 3, disulfide bond 3, peptide 2, signal peptide 1, turn 1, propeptide 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2H8B	SOLUTION NMR
2K6T	SOLUTION NMR
2K6U	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51460-F1	66.25	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 34–116, 46–129, 115–120

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-444821	Relaxin receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 281 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, BROWNE_HCMV_INFECTION_4HR_UP, MODULE_97, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, MODULE_182, GOBP_MALE_GAMETE_GENERATION, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_CELL_CELL_SIGNALING, GOBP_WOUND_HEALING, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS

GO Biological Process (5): adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), cell-cell signaling (GO:0007267), spermatogenesis (GO:0007283), positive regulation of epithelial cell migration (GO:0010634), positive regulation of wound healing (GO:0090303)

GO Molecular Function (5): protease binding (GO:0002020), signaling receptor binding (GO:0005102), insulin receptor binding (GO:0005158), hormone activity (GO:0005179), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Peptide ligand-binding receptors	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
cell communication	1
signaling	1
developmental process involved in reproduction	1
male gamete generation	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
enzyme binding	1
protein binding	1
signaling receptor binding	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INSL3	RXFP2	Q8WXD0	999
INSL3	RXFP1	Q9HBX9	994
INSL3	RLN1	P04808	948
INSL3	RLN2	P04090	918
INSL3	INSL4	Q14641	908
INSL3	AMH	P03971	869
INSL3	RLN3	Q8WXF3	863
INSL3	CYP17A1	P05093	811
INSL3	INS	P01308	806
INSL3	HSD17B3	P37058	796
INSL3	NR5A1	Q13285	775
INSL3	CYP11A1	P05108	765
INSL3	RXFP3	Q9NSD7	763
INSL3	RXFP4	Q8TDU9	744
INSL3	LHCGR	P22888	741

IntAct

8 interactions, top by confidence:

A	B	Type	Score
INSL3	C12orf57	psi-mi:“MI:0915”(physical association)	0.560
INSL3	GAPDHS	psi-mi:“MI:0914”(association)	0.530
INSL3	ARPC4-TTLL3	psi-mi:“MI:0914”(association)	0.350
ADRM1	POTEF	psi-mi:“MI:0914”(association)	0.350
C12orf57	INSL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): MBD3 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), IREB2 (Affinity Capture-MS), RNF123 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), MTERF4 (Affinity Capture-MS), MTERF4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), RNF123 (Affinity Capture-MS), IREB2 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: A0MLS4, A2BDG0, A2BDG5, A2BDG9, A2RRL7, A3KN25, A6NGB7, G1TZA0, O14669, O77751, O77801, O95868, P01286, P02820, P02822, P0DUJ6, P24807, P25063, P27177, P41547, P51460, P63292, P98162, Q01524, Q08DF2, Q1ECT8, Q1JPW9, Q496H8, Q58CU5, Q5CZK3, Q5G860, Q5G863, Q5HZE8, Q60549, Q64697, Q6BEG6, Q7TPG6, Q8C4W3, Q8R182, Q923S2

Diamond homologs: O09107, O77801, O97937, P51460, P51461, Q5CZK3, Q6X7V3, Q9WUG6, Q9WUK0, P01349, P11952, P11953, P81191, Q5CZK2, Q8BFS3, Q8CHK2, Q8HY17, Q8WXF3, Q9WV41

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

261 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	211
Likely benign	11
Benign	20

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
14829	NM_005543.4(INSL3):c.330C>G (p.Asn110Lys)	Pathogenic
14830	NM_005543.4(INSL3):c.278C>T (p.Pro93Leu)	Pathogenic
14831	NM_005543.4(INSL3):c.304C>T (p.Arg102Cys)	Pathogenic
37092	NM_005543.4(INSL3):c.217C>T (p.Arg73Ter)	Pathogenic
2429748	NM_005543.4(INSL3):c.143dup (p.Arg50fs)	Likely pathogenic
4279048	NM_005543.4(INSL3):c.176_182del (p.Ala59fs)	Likely pathogenic
521489	NM_005543.4(INSL3):c.148dup (p.Arg50fs)	Likely pathogenic

SpliceAI

363 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17821315:A:AC	donor_gain	1.0000
19:17821316:C:CC	donor_gain	1.0000
19:17817055:CTCAC:C	acceptor_gain	0.9900
19:17817077:CTCAG:C	acceptor_gain	0.9900
19:17821312:CTCA:C	donor_loss	0.9900
19:17821314:CACG:C	donor_loss	0.9900
19:17821315:A:C	donor_loss	0.9900
19:17821316:CG:C	donor_gain	0.9900
19:17821316:CGGT:C	donor_gain	0.9900
19:17821324:T:TA	donor_gain	0.9900
19:17821338:T:TA	donor_gain	0.9900
19:17821311:A:AC	donor_gain	0.9800
19:17821311:AC:A	donor_loss	0.9800
19:17821312:C:CC	donor_gain	0.9800
19:17821315:ACGGT:A	donor_gain	0.9800
19:17821316:CGGTC:C	donor_gain	0.9800
19:17817057:CAC:C	acceptor_gain	0.9700
19:17817058:ACCT:A	acceptor_loss	0.9700
19:17817060:C:CA	acceptor_loss	0.9700
19:17817061:T:A	acceptor_loss	0.9700
19:17817079:CAG:C	acceptor_gain	0.9600
19:17817056:TCAC:T	acceptor_gain	0.9400
19:17817057:CACC:C	acceptor_gain	0.9400
19:17821316:CGG:C	donor_gain	0.9400
19:17821284:C:A	donor_gain	0.9200
19:17821413:T:TA	donor_gain	0.9200
19:17817060:C:CC	acceptor_gain	0.9100
19:17817713:TGA:T	donor_gain	0.9100
19:17817078:TCAG:T	acceptor_gain	0.9000
19:17817079:CAGC:C	acceptor_gain	0.9000

AlphaMissense

824 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17821354:C:A	W51C	0.990
19:17821354:C:G	W51C	0.990
19:17821370:C:T	C46Y	0.984
19:17821394:A:C	F38C	0.984
19:17816895:C:A	G119C	0.979
19:17821394:A:G	F38S	0.978
19:17816891:C:G	C120S	0.976
19:17816892:A:T	C120S	0.976
19:17821370:C:G	C46S	0.974
19:17821371:A:T	C46S	0.974
19:17816864:C:G	C129S	0.973
19:17816865:A:T	C129S	0.973
19:17821371:A:G	C46R	0.971
19:17816906:C:G	C115S	0.970
19:17816907:A:T	C115S	0.970
19:17816864:C:T	C129Y	0.968
19:17816865:A:G	C129R	0.968
19:17821370:C:A	C46F	0.968
19:17816905:G:C	C115W	0.966
19:17816906:C:T	C115Y	0.965
19:17816892:A:G	C120R	0.962
19:17816903:C:G	C116S	0.961
19:17816904:A:T	C116S	0.961
19:17821369:G:C	C46W	0.961
19:17816903:C:T	C116Y	0.959
19:17816863:A:C	C129W	0.958
19:17816891:C:T	C120Y	0.957
19:17816902:G:C	C116W	0.957
19:17821406:C:T	C34Y	0.956
19:17816904:A:G	C116R	0.954

dbSNP variants (sampled 300 via entrez): RS1000052852 (19:17819489 C>T), RS1000083714 (19:17819828 C>A,G,T), RS1000129052 (19:17821364 C>A,G,T), RS1000150153 (19:17821900 TTATTTTTTATTTTTA>T), RS1000776479 (19:17817410 A>G), RS1001125841 (19:17822978 G>A), RS1001407955 (19:17818944 G>A), RS1001870946 (19:17823330 A>G,T), RS1002080299 (19:17818309 C>T), RS1002625630 (19:17817745 G>A,T), RS1002680333 (19:17819183 G>A), RS1002759858 (19:17820878 A>G), RS1003408224 (19:17822057 G>A), RS1003887 (19:17816591 C>A,G,T), RS1004001836 (19:17818374 G>C)

Disease associations

OMIM: gene MIM:146738 | disease phenotypes: MIM:219050

GenCC curated gene-disease

Disease	Classification	Inheritance
cryptorchidism	Moderate	Autosomal dominant

Mondo (1): cryptorchidism (MONDO:0009047)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000104	Renal agenesis
HP:0012741	Unilateral cryptorchidism

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003262_363	Post bronchodilator FEV1	2.000000e-06
GCST003264_991	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST007202_7	High density lipoprotein cholesterol levels	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Valproic Acid	increases methylation, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
testosterone enanthate	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
butyraldehyde	increases expression	1
bisphenol A diglycidyl ether	increases expression	1
pentanal	increases expression	1
cetrorelix	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Carmustine	decreases expression	1
Estradiol	decreases reaction, decreases expression	1
Ozone	affects expression, increases abundance	1
Testosterone	decreases expression, decreases reaction, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Levonorgestrel	affects cotreatment, decreases expression	1
Desogestrel	decreases expression, affects cotreatment	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

31 trials via MONDO — disease-level, not drug-specific.

Trial	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
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)
NCT04342026	Not specified	RECRUITING	Role of the Environment and Endocrine Disruptors in Child Cryptorchidism
NCT04528381	Not specified	UNKNOWN	Role of Laparoscopy in Management of Non-palpable Undescended Testis : Assuit University Experience
NCT05097820	Not specified	RECRUITING	Prospective Observational Study on SEBBIN Silicone Gel-filled Testicular Implants
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.
NCT06558994	Not specified	RECRUITING	Transection Versus Ligation of Internal Spermatic Vessels in Laparoscopic Fowler-Stephens Orchidopexy
NCT06560086	Not specified	UNKNOWN	Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Macrophage Trem2
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.
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
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