HOXD13

Summary

HOXD13 (homeobox D13, HGNC:5136) is a protein-coding gene on chromosome 2q31.1, encoding Homeobox protein Hox-D13 (P35453). Sequence-specific transcription factor that binds gene promoters and activates their transcription. It is a selective cancer dependency (DepMap: 13.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5’ end of this cluster have been associated with severe limb and genital abnormalities. Mutations in this particular gene cause synpolydactyly.

Source: NCBI Gene 3239 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brachydactyly-syndactyly syndrome (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 188 total — 28 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 97
• Cancer dependency (DepMap): dependent in 13.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 21 downstream targets (CollecTRI)
• MANE Select transcript: NM_000523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5136
Approved symbol	HOXD13
Name	homeobox D13
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000128714
Ensembl biotype	protein_coding
OMIM	142989
Entrez	3239

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000392539

RefSeq mRNA: 1 — MANE Select: NM_000523 NM_000523

CCDS: CCDS2264

Canonical transcript exons

ENST00000392539 — 2 exons

Exon	Start	End
ENSE00000882905	176092721	176093671
ENSE00001272192	176094480	176095944

Expression profiles

Bgee: expression breadth broad, 47 present calls, max score 82.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4270 / max 42.4460, expressed in 135 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23817	0.1844	59
23818	0.1503	83
23816	0.0923	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	82.98	gold quality
vagina	UBERON:0000996	82.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.57	gold quality
ectocervix	UBERON:0012249	81.50	gold quality
calcaneal tendon	UBERON:0003701	79.12	gold quality
sigmoid colon	UBERON:0001159	77.63	gold quality
seminal vesicle	UBERON:0000998	76.66	gold quality
prostate gland	UBERON:0002367	75.79	gold quality
endocervix	UBERON:0000458	74.27	gold quality
mammalian vulva	UBERON:0000997	71.50	gold quality
tendon	UBERON:0000043	69.57	gold quality
rectum	UBERON:0001052	69.33	gold quality
uterine cervix	UBERON:0000002	67.64	gold quality
parotid gland	UBERON:0001831	67.10	gold quality
endothelial cell	CL:0000115	65.85	gold quality
heart right ventricle	UBERON:0002080	65.00	gold quality
nasal cavity epithelium	UBERON:0005384	64.80	gold quality
buccal mucosa cell	CL:0002336	64.52	gold quality
colonic mucosa	UBERON:0000317	60.60	silver quality
mucosa of sigmoid colon	UBERON:0004993	60.47	silver quality
lower lobe of lung	UBERON:0008949	60.37	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.26	gold quality
secondary oocyte	CL:0000655	59.43	gold quality
vastus lateralis	UBERON:0001379	58.99	gold quality
quadriceps femoris	UBERON:0001377	58.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	58.60	gold quality
pericardium	UBERON:0002407	58.24	gold quality
large intestine	UBERON:0000059	58.03	gold quality
colon	UBERON:0001155	57.83	gold quality
cerebellar vermis	UBERON:0004720	57.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	yes	721.04
E-ANND-3	no	1.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

21 targets.

Target	Regulation
BARX1	Repression
BMP2
BMP4	Activation
CASP8AP2
CYP1A1
DACH1	Activation
EMX2
EPHA3	Repression
EPHA4	Repression
EPHA7	Activation
FBN1	Activation
FHL1	Unknown
H1-6
HAND2	Activation
HOXA13
HOXD13
IL6
NGEF
SALL1	Repression
SALL3	Repression
SFRP1

JASPAR motifs

Motif	Name	Family
MA0909.1	HOXD13	HOX
MA0909.2	HOXD13	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): EZH2, FOXC1, GLI3, HOXD13, MYC

miRNA regulators (miRDB)

128 targeting HOXD13, 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-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 13.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly (PMID:11778160)
• Data show that a mutant HOXD13 protein that recognizes only a subset of sites recognized by the wild-type protein causes a novel human limb malformation. (PMID:12620993)
• Missense mutations in this protein are associated with brachydactyly types D and E. (PMID:12649808)
• This is the first report on prenatal diagnosis of Synpolydactyly by detecting the HOXD13 polyalanine expansion in the Han population of the Chinese mainland. (PMID:15696469)
• Results suggest that synpolydactyly in this kindred may be caused by polyalanine expansion in HOXD13. (PMID:15952114)
• Data show that HOXD13 are important susceptible genes of idiopathic congenital talipes equinovarus. (PMID:16331564)
• synergism between NUP98-HOX and wt-Flt3 is the result of the ability of Flt3 to increase proliferation of myeloid progenitors blocked in differentiation by NUP98-HOX fusions, revealing a direct role for wt-Flt3 in the pathobiology of AML. (PMID:16861351)
• There is a link between HOXD13 and two additional limb phenotypes–syndactyly type V and brachydactyly type A4–and demonstrated that a polyalanine contraction in HOXD13, most likely, led to other digital anomalies but not to synpolydactyly. (PMID:17236141)
• findings strongly suggest that specific mutations in HOXD13 gene may cause both hypoplastic synpolydactyly and hypospadias (PMID:17656229)
• Early human development shows spatiotemporal differences of HOXD13 expression in the endodermal and mesodermal structures. (PMID:17853405)
• We showed that SPD1 phenotype segregates with an identical expansion mutation of 21 bp in HOXD13. We show that HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, is without clinical consequences. (PMID:18072967)
• The results shows that HOXD13 gene mutation was not involved in outbreak in idiopathic congenital talipes equinovarus, but changes of HOXD13 and FHL1 gene expression related to the development of talipes equinovarus malformation. (PMID:18244901)
• analysis of HOXD13 in 100 patients with limb malformations; 7 novel mutations in the coding region & 2 novel mutations in the 5’-untranslated region were identified (PMID:18399101)
• transgenic mice expressing NUP98-HOXD13 (NHD13) fusion gene develop myelodysplastic syndrome, and more than half eventually progress to acute leukemia (PMID:18566322)
• Hoxd13 and Fhl1 were expressed in the interdigital tissues of E12.5 rat embryo. Luciferase assay and EMSA identified a novel promoter region of Fhl1 that directly interacts with Hoxd13 (PMID:18758158)
• G220V missense mutation of HOXD13 caused synpolydactyly in a Greek family. (PMID:19060004)
• Detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer. (PMID:19488988)
• data show no significant difference in HOXD11, HOXD12 & HOXD13 genotype frequencies between the autism spectrum disorder & healthy controls, but one SNP in promoter region of HOXD11 was observed in only 4 patients with ASD (PMID:19540081)
• results expand the spectrum of HOXD13 mutations;suggest that not only the size of the polyalanine repeat but also other unknown factors might play a role in synpolydactyly (PMID:19686284)
• Geminin, which interacts with HOXD13 as well, blocks HOXD13-mediated assembly of pre-replication complex proteins and inhibits HOXD13-induced DNA replication. (PMID:19703996)
• a duplication mutation, c. 186-212dup, in exon 1 of the HOXD13 gene in the affected individuals in a Chinese family with unusual clinical manifestations of synpolydactyly (PMID:20974300)
• Variable skeletal phenotype in 2q31 deletion patients is a result of hemizygosity for the HOXD genes. (PMID:21068127)
• results show the first nonsense mutation in the HOXD13 gene underlying a severe form of SPD in the homozygous state, and a milder form of SPD with approximately 50% penetrance in the heterozygous state. (PMID:21814222)
• HOXD13 gene mutation was responsible for the synpolydactyly (SPD) phenotype in this family. (PMID:22161087)
• Misexpression of HOXD13(G11A) in the developing chick limb phenocopied the human SPD phenotype (PMID:22373878)
• This finding expands the phenotypic spectrum associated with HOXD13 mutations and advances our understanding of human limb development. (PMID:22374128)
• Correlation between Synpolydactyly and alanine expansion in HOXD13. (PMID:22406499)
• findings show that expression of NUP98-HOXD13 impairs class switch recombination and reduces the antibody-mediated immune response, in addition to its role in leukemia (PMID:22613470)
• Identification of a novel c.659G>C (p.Gly220Ala) mutation outside the HOXD13 homeodomain responsible for synpolydactyly in a Chinese family. (PMID:23948678)
• Data indicate increased levels of reactive oxygen species (ROS) were detected in bone marrow nucleated cells (BMNC) that express CD71 in in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for myelodysplastic syndromes (MDS). (PMID:23958061)
• A genome-wide array-comparative genomic hybridization (aCGH) analysis revealed global chromosomal aberration in MWCNTs-treated clones, predominantly at chromosome 2q31-32, where the potential oncogenes HOXD9 and HOXD13 are located (PMID:23984819)
• Molecular characteristics of a HOXD13 synpolydactyly 1 nonsense mutation in a Chinese family. (PMID:24055421)
• Linkage analysis of the syndactyly type 1 subtype c (SD1-c) phenotype based on two Chinese families with 3/4 fingers syndactyly shows that two missense mutations in codon 306 of HOXD13 underlie SD1-c. (PMID:24789103)
• A 27 bp expansion mutation in exon 1 of HOXD13 was associated with autosomal dominant synpolydactyly in a Chinese family. (PMID:26252089)
• A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation. (PMID:26581570)
• HOXD13 methylation is a common event in primary breast cancer and is associated with poor survival of breast cancer patients. (PMID:26617782)
• down-regulation of HOXD13 might be a potentially useful prognostic marker for patients with breast cancer. (PMID:26617867)
• a novel mutation causing truncation of HOXD13 protein was successfully identified as being associated with an atypical non-syndromic SPD phenotype in our study. (PMID:27254532)
• Knock down of the dickkopf WNT signaling pathway inhibitor 2 (DKK2) resulted in a significant suppression of HOXD10, HOXD11 and HOXD13 while over-expression of DKK2 and stimulation with factors of the WNT signaling pathway. (PMID:27363011)
• The results suggest that the c.917G>A (p.R306Q) mutation in the HOXD13 gene, may be responsible for syndactyly type Ic in this family. (PMID:28498426)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hoxd13	ENSMUSG00000001819
rattus_norvegicus	Hoxd13	ENSRNOG00000001588

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-D13 — P35453 (reviewed: P35453)

Alternative names: Homeobox protein Hox-4I

All UniProt accessions (1): P35453

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor that binds gene promoters and activates their transcription. Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subcellular location. Nucleus.

Disease relevance. Synpolydactyly 1 (SPD1) [MIM:186000] Limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. The disease is caused by variants affecting the gene represented in this entry. Brachydactyly D (BDD) [MIM:113200] A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type D is characterized by short and broad terminal phalanges of the thumbs and big toes. The disease is caused by variants affecting the gene represented in this entry. Syndactyly 5 (SDTY5) [MIM:186300] A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. The characteristic finding in SDTY5 is the presence of an associated metacarpal and metatarsal fusion. The metacarpals and metatarsals most commonly fused are the 4th and 5th or the 3rd and 4th. Soft tissue syndactyly usually affects the 3rd and 4th fingers and the 2nd and 3rd toes. The disease is caused by variants affecting the gene represented in this entry. Brachydactyly-syndactyly syndrome (BDSD) [MIM:610713] A disease characterized by generalized shortening of the hands and feet, broad and short distal phalanges of the thumbs, and cutaneous syndactyly of toes 2 and 3. The limb phenotypes observed in this syndrome overlap those of brachydactyly types A4, D, E and syndactyly type 1. The disease is caused by variants affecting the gene represented in this entry. Brachydactyly E1 (BDE1) [MIM:113300] A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. Brachydactyly type E1 is characterized by shortening limited to fourth metacarpals and/or metatarsals. The disease is caused by variants affecting the gene represented in this entry. VACTERL association (VACTERL) [MIM:192350] VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. The gene represented in this entry may be involved in disease pathogenesis. Brachydactyly-syndactyly-oligodactyly syndrome (BDSDO) [MIM:610713] A syndrome characterized by a complex brachydactyly-syndactyly-oligodactyly phenotype. Limb anomalies include reduced number of digits that are severely shortened, camptodactyly, syndactyly, absence of terminal phalanges of the thumbs, and absence of nails of the thumbs and toes. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. The poly-Ala region is polymorphic (11 to 15 residues) in the normal population and is expanded to about 22-29 residues in SPD1 and syndactyly type 5 patients.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_000514* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR022067	HoxA13_N	Domain
IPR051003	AP_axis_regulatory_Homeobox	Family

Pfam: PF00046, PF12284

UniProt features (17 total): sequence variant 12, region of interest 2, chain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35453-F1	57.18	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 453 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_MALE_GENITALIA_DEVELOPMENT, GOBP_BRANCH_ELONGATION_OF_AN_EPITHELIUM, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN

GO Biological Process (20): skeletal system development (GO:0001501), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), anterior/posterior pattern specification (GO:0009952), male genitalia development (GO:0030539), response to testosterone (GO:0033574), regulation of cell population proliferation (GO:0042127), embryonic digit morphogenesis (GO:0042733), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic hindgut morphogenesis (GO:0048619), prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis (GO:0060527), morphogenesis of an epithelial fold (GO:0060571), branch elongation of an epithelium (GO:0060602), regulation of branching involved in prostate gland morphogenesis (GO:0060687), pattern specification process (GO:0007389), gland morphogenesis (GO:0022612), embryonic limb morphogenesis (GO:0030326), prostate gland development (GO:0030850), limb morphogenesis (GO:0035108)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA-templated transcription	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
embryonic morphogenesis	2
regulation of transcription by RNA polymerase II	2
branching involved in prostate gland morphogenesis	2
gland development	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
system development	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regionalization	1
male sex differentiation	1
genitalia development	1
reproductive system development	1
response to lipid	1
response to ketone	1
cell population proliferation	1
regulation of cellular process	1
embryonic limb morphogenesis	1
positive regulation of DNA-templated transcription	1
hindgut morphogenesis	1
prostate glandular acinus morphogenesis	1
morphogenesis of an epithelium	1
axis elongation	1
morphogenesis of a branching epithelium	1
regulation of morphogenesis of a branching structure	1
regulation of morphogenesis of an epithelium	1
regulation of reproductive process	1
multicellular organism development	1
multicellular organismal process	1
animal organ morphogenesis	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
urogenital system development	1
reproductive structure development	1
appendage morphogenesis	1
limb development	1

Protein interactions and networks

STRING

1294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXD13	SHH	Q15465	869
HOXD13	SPDL1	Q96EA4	868
HOXD13	NUP98	P52948	829
HOXD13	CD274	Q9NZQ7	726
HOXD13	PDCD1LG2	Q9BQ51	702
HOXD13	PRRX1	P54821	674
HOXD13	FBLN1	P23142	663
HOXD13	PHF23	Q9BUL5	641
HOXD13	SHOX2	O60902	633
HOXD13	GLI3	P10071	627
HOXD13	DDX10	Q13206	621
HOXD13	PRSS53	Q2L4Q9	605
HOXD13	HOXD10	P28358	600
HOXD13	ZP2	Q05996	599
HOXD13	HOXD11	P31277	593

IntAct

53 interactions, top by confidence:

A	B	Type	Score
TNFSF14	TMEM11	psi-mi:“MI:0914”(association)	0.670
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
GPR55	LGALS3	psi-mi:“MI:0914”(association)	0.530
DGCR2	HOXD13	psi-mi:“MI:0914”(association)	0.530
HOXD13	EEF1D	psi-mi:“MI:0914”(association)	0.530
CREB1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOS	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXA1	NFIC	psi-mi:“MI:0914”(association)	0.350
FOXA2	FOXN2	psi-mi:“MI:0914”(association)	0.350
FOXA3	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXC1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXC2	ZNF536	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXF1	HOXB9	psi-mi:“MI:0914”(association)	0.350
FOXI2	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXN1	FOXN1	psi-mi:“MI:0914”(association)	0.350
FOXQ1	DDX39A	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
F9	DDX11L8	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
IQCN	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS)

ESM2 similar proteins: A1A5R1, A2YXQ1, A4F5G6, A6NFN3, A6QPR6, E3WDQ9, O42366, O43251, O65034, O80416, P24344, P35453, P46609, P55316, P56260, P70217, Q00939, Q02962, Q0VD23, Q14671, Q17QD3, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q1KKX5, Q27002, Q2VB19, Q5NVN8, Q5R5X3, Q60987, Q642J5, Q66JB7, Q66KI6, Q6YHU8, Q6ZBH6, Q6ZK57, Q7TN99

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, G5EFY5, O14627, O42502, O42506, O43248, P02835, P09013, P09067, P09079, P09087, P09631, P09633, P10038, P10179, P17482, P17919, P20615, P23812, P24061, P24341, P24342, P24343, P24344, P28358, P28359, P31257, P31260, P31263, P31268, P31269, P31271, P31272, P31274, P31275

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HOXD13	“up-regulates quantity by expression”	EPHA7	“transcriptional regulation”
HOXD13	“up-regulates activity”	MEIS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
somitogenesis	6	33.0×	4e-06
anatomical structure morphogenesis	9	18.4×	4e-07
Notch signaling pathway	6	12.5×	7e-04
chromatin organization	6	8.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	3
Uncertain significance	106
Likely benign	18
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1332838	NM_000523.4(HOXD13):c.708del (p.Asn236fs)	Pathogenic
1451293	NM_000523.4(HOXD13):c.186_212dup (p.Ala63_Ala71dup)	Pathogenic
1452333	NM_000523.4(HOXD13):c.542_552del (p.Asn181fs)	Pathogenic
1453451	NM_000523.4(HOXD13):c.314_315del (p.Lys105fs)	Pathogenic
14867	NM_000523.4(HOXD13):c.323_336del (p.Pro108fs)	Pathogenic
14868	NM_000523.4(HOXD13):c.834del (p.Lys279fs)	Pathogenic
14869	NM_000523.4(HOXD13):c.964A>C (p.Ile322Leu)	Pathogenic
14871	NM_000523.4(HOXD13):c.782-2del	Pathogenic
14873	NM_000523.4(HOXD13):c.209_210insGGCTGCGGCGGCGGCAGCGGC (p.Ala65_Ala71dup)	Pathogenic
14874	NM_000523.4(HOXD13):c.974A>G (p.Gln325Arg)	Pathogenic
14875	NM_000523.4(HOXD13):c.183_203del (p.Ala65_Ala71del)	Pathogenic
14876	NM_000523.4(HOXD13):c.683G>T (p.Gly228Val)	Pathogenic
1919465	NM_000523.4(HOXD13):c.183_203dup (p.Ala71_Ser72insAlaAlaAlaAlaAlaAlaAla)	Pathogenic
225650	NM_000523.4(HOXD13):c.742C>T (p.Gln248Ter)	Pathogenic
225652	NM_000523.4(HOXD13):c.917G>A (p.Arg306Gln)	Pathogenic
225653	NM_000523.4(HOXD13):c.781+1G>A	Pathogenic
225654	NM_000523.4(HOXD13):c.683G>C (p.Gly228Ala)	Pathogenic
225655	NM_000523.4(HOXD13):c.973C>A (p.Gln325Lys)	Pathogenic
225656	NM_000523.4(HOXD13):c.916C>G (p.Arg306Gly)	Pathogenic
2502140	NM_000523.4(HOXD13):c.684dup (p.Tyr229fs)	Pathogenic
3252671	NM_000523.4(HOXD13):c.206_207insAGCGGCGGCTGCGGCGGCGGCAGC (p.Ala71_Ser72insAlaAlaAlaAlaAlaAlaAlaAla)	Pathogenic
3256389	NM_000523.4(HOXD13):c.212_213insTGCCGCCGCCGCAGCCGCCGCTGCCGC (p.Ala71_Ser72insAlaAlaAlaAlaAlaAlaAlaAlaAla)	Pathogenic
3346356	NM_000523.4(HOXD13):c.858del (p.Gln287fs)	Pathogenic
3382450	NM_000523.4(HOXD13):c.673del (p.Ser225fs)	Pathogenic
3728565	NM_000523.4(HOXD13):c.663_664del (p.Glu221fs)	Pathogenic
4271933	NM_000523.4(HOXD13):c.461C>A (p.Ser154Ter)	Pathogenic
689765	NM_000523.4(HOXD13):c.744_747del (p.Gln248fs)	Pathogenic
916250	NM_000523.4(HOXD13):c.212_213insGGCGGCTGCGGCGGCGGCAGCGGCAGC (p.Ala63_Ala71dup)	Pathogenic
1324539	NM_000523.4(HOXD13):c.203_204insA (p.Ala69fs)	Likely pathogenic
2499278	NM_000523.4(HOXD13):c.938C>G (p.Thr313Arg)	Likely pathogenic

SpliceAI

179 predictions. Top by Δscore:

Variant	Effect	Δscore
2:176094477:CAG:C	acceptor_loss	1.0000
2:176094478:AGG:A	acceptor_gain	1.0000
2:176094479:GGG:G	acceptor_gain	1.0000
2:176093667:TCCAG:T	donor_loss	0.9900
2:176093668:CCAG:C	donor_loss	0.9900
2:176093669:CAGGT:C	donor_loss	0.9900
2:176093670:AGGTA:A	donor_loss	0.9900
2:176093671:GG:G	donor_loss	0.9900
2:176093672:GT:G	donor_loss	0.9900
2:176093673:T:A	donor_loss	0.9900
2:176094468:T:TA	acceptor_gain	0.9900
2:176094475:A:AG	acceptor_gain	0.9900
2:176094475:ATCAG:A	acceptor_gain	0.9900
2:176094476:T:G	acceptor_gain	0.9900
2:176094478:A:AG	acceptor_gain	0.9900
2:176094478:AG:A	acceptor_gain	0.9900
2:176094478:AGGG:A	acceptor_gain	0.9900
2:176094479:G:GG	acceptor_gain	0.9900
2:176094479:GG:G	acceptor_gain	0.9900
2:176094479:GGGG:G	acceptor_gain	0.9900
2:176093455:G:GT	donor_gain	0.9800
2:176094472:T:A	acceptor_gain	0.9800
2:176093576:ACC:A	donor_gain	0.9700
2:176094472:T:TA	acceptor_loss	0.9700
2:176094476:TCAGG:T	acceptor_gain	0.9700
2:176094477:CA:C	acceptor_gain	0.9700
2:176094478:A:C	acceptor_gain	0.9700
2:176094479:GGGGA:G	acceptor_gain	0.9700
2:176094474:TATCA:T	acceptor_gain	0.9600
2:176094479:G:T	acceptor_gain	0.9600

AlphaMissense

2191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:176094528:G:T	R277M	1.000
2:176094529:G:C	R277S	1.000
2:176094529:G:T	R277S	1.000
2:176094530:A:G	K278E	1.000
2:176094532:G:C	K278N	1.000
2:176094532:G:T	K278N	1.000
2:176094537:G:C	R280T	1.000
2:176094538:A:C	R280S	1.000
2:176094538:A:T	R280S	1.000
2:176094543:C:A	P282H	1.000
2:176094545:T:A	Y283N	1.000
2:176094545:T:C	Y283H	1.000
2:176094545:T:G	Y283D	1.000
2:176094546:A:G	Y283C	1.000
2:176094549:C:T	T284I	1.000
2:176094558:A:G	Q287R	1.000
2:176094559:G:C	Q287H	1.000
2:176094559:G:T	Q287H	1.000
2:176094561:T:A	L288H	1.000
2:176094561:T:C	L288P	1.000
2:176094570:T:A	L291Q	1.000
2:176094570:T:C	L291P	1.000
2:176094570:T:G	L291R	1.000
2:176094573:A:T	E292V	1.000
2:176094574:G:C	E292D	1.000
2:176094574:G:T	E292D	1.000
2:176094581:T:C	Y295H	1.000
2:176094581:T:G	Y295D	1.000
2:176094582:A:C	Y295S	1.000
2:176094582:A:G	Y295C	1.000

dbSNP variants (sampled 300 via entrez): RS1000616285 (2:176091021 C>T), RS1000890848 (2:176091280 G>A), RS1000944462 (2:176095478 T>G), RS1000977286 (2:176095710 T>A), RS1000986290 (2:176086701 G>A), RS1001133189 (2:176089709 G>A,C), RS1001164454 (2:176091985 T>C), RS1001216914 (2:176092288 G>A), RS1001303211 (2:176089178 C>CT), RS1001368765 (2:176086070 T>A), RS1001502598 (2:176089221 T>C,G), RS1003168782 (2:176089153 A>G), RS1003221054 (2:176089545 G>A), RS1003284229 (2:176095995 G>A), RS1003422511 (2:176095630 G>A,C,T)

Disease associations

OMIM: gene MIM:142989 | disease phenotypes: MIM:610713, MIM:113200, MIM:113300, MIM:186000, MIM:186300, MIM:192350, MIM:603596

GenCC curated gene-disease

Disease	Classification	Inheritance
brachydactyly-syndactyly syndrome	Definitive	Autosomal dominant
synpolydactyly type 1	Strong	Autosomal dominant
syndactyly type 5	Strong	Autosomal dominant
brachydactyly type D	Strong	Autosomal dominant
brachydactyly type E1	Strong	Autosomal dominant
brachydactyly type E	Supportive	Autosomal dominant

Mondo (15): brachydactyly-syndactyly syndrome (MONDO:0012544), brachydactyly type D (MONDO:0007222), brachydactyly type E1 (MONDO:0007223), synpolydactyly type 1 (MONDO:0008513), syndactyly type 5 (MONDO:0008516), brachydactyly type E (MONDO:0019677), VACTERL/vater association (MONDO:0008642), brachydactyly-syndactyly-oligodactyly syndrome (MONDO:0800344), skeletal dysplasia (MONDO:0018230), intellectual disability (MONDO:0001071), oligospermia (MONDO:0001913), male infertility (MONDO:0005372), syndactyly (MONDO:0021002), polydactyly (MONDO:0021003), synpolydactyly (MONDO:0021651)

Orphanet (9): Brachydactyly-syndactyly, Zhao type (Orphanet:93409), Synpolydactyly type 1 (Orphanet:295195), Brachydactyly type E (Orphanet:93387), Syndactyly type 5 (Orphanet:93406), VACTERL/VATER association (Orphanet:887), Primary bone dysplasia (Orphanet:364526), Syndactyly type 2 (Orphanet:93403), NON RARE IN EUROPE: Brachydactyly type D (Orphanet:93385), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

97 total (30 of 97 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000062	Ambiguous genitalia
HP:0000086	Ectopic kidney
HP:0000104	Renal agenesis
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000239	Large fontanelles
HP:0000256	Macrocephaly
HP:0000311	Round face
HP:0000358	Posteriorly rotated ears
HP:0000772	Abnormal rib morphology
HP:0000776	Congenital diaphragmatic hernia
HP:0000795	Abnormality of the urethra
HP:0000894	Short clavicles
HP:0001032	Absent distal interphalangeal creases
HP:0001048	Cavernous hemangioma
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001177	Preaxial hand polydactyly
HP:0001195	Single umbilical artery
HP:0001382	Joint hypermobility
HP:0001440	Metatarsal synostosis
HP:0001501	6 metacarpals
HP:0001511	Intrauterine growth retardation
HP:0001539	Omphalocele

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006661_148	Male-pattern baldness	3.000000e-18

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600
D013576	Syndactyly	C05.116.099.370.894.819; C05.660.585.800; C05.660.906.819; C16.131.621.585.800; C16.131.621.906.819
C562420	Brachydactyly, Type D (supp.)
C566194	Brachydactyly, Type E (supp.)
C565193	Brachydactyly-Syndactyly Syndrome (supp.)
C538153	Syndactyly, type 2 (supp.)
C538155	Syndactyly, type v (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Valproic Acid	increases expression, increases methylation	2
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Vitallium	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3B1	SEES3-1V human HOXD13, clone1	Embryonic stem cell	Male
CVCL_A3B2	SEES3-1V human HOXD13, clone2	Embryonic stem cell	Male
CVCL_A3B3	SEES3-1V human HOXD13, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine