C14orf39

Summary

C14orf39 (chromosome 14 open reading frame 39, HGNC:19849) is a protein-coding gene on chromosome 14q23.1, encoding Protein SIX6OS1 (Q8N1H7). Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination.

Involved in homologous chromosome pairing at meiosis. Predicted to be located in chromosome. Predicted to be active in central element. Implicated in primary ovarian insufficiency 18 and spermatogenic failure 52.

Source: NCBI Gene 317761 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 52 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 176 total — 12 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_174978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19849
Approved symbol	C14orf39
Name	chromosome 14 open reading frame 39
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	SIX6OS1
Ensembl gene	ENSG00000179008
Ensembl biotype	protein_coding
OMIM	617307
Entrez	317761

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 nonsense_mediated_decay

ENST00000321731, ENST00000498565, ENST00000555476, ENST00000556799, ENST00000557138, ENST00000917632, ENST00000917633, ENST00000917634, ENST00000917635

RefSeq mRNA: 1 — MANE Select: NM_174978 NM_174978

CCDS: CCDS9746

Canonical transcript exons

ENST00000321731 — 18 exons

Exon	Start	End
ENSE00001223451	60468445	60468536
ENSE00001223460	60469533	60469653
ENSE00001223468	60471417	60471459
ENSE00001223479	60471552	60471739
ENSE00001223487	60478300	60478389
ENSE00001223495	60483691	60483817
ENSE00001223518	60435956	60437047
ENSE00001223525	60485030	60485086
ENSE00001366373	60485945	60486063
ENSE00003476060	60456917	60457095
ENSE00003494853	60484881	60484937
ENSE00003570905	60461508	60461593
ENSE00003593909	60442074	60442131
ENSE00003596957	60458678	60458739
ENSE00003598427	60466917	60467044
ENSE00003600359	60455001	60455145
ENSE00003639185	60465979	60466055
ENSE00003640302	60461354	60461412

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 82.67.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7404 / max 35.7857, expressed in 243 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143507	0.7404	243

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.47	gold quality
adenohypophysis	UBERON:0002196	80.35	gold quality
pituitary gland	UBERON:0000007	77.95	gold quality
calcaneal tendon	UBERON:0003701	77.17	gold quality
right testis	UBERON:0004534	77.08	gold quality
left testis	UBERON:0004533	76.73	gold quality
testis	UBERON:0000473	76.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.74	gold quality
muscle of leg	UBERON:0001383	71.86	gold quality
gastrocnemius	UBERON:0001388	71.60	gold quality
secondary oocyte	CL:0000655	68.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	65.28	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	64.86	gold quality
tendon	UBERON:0000043	64.14	gold quality
deltoid	UBERON:0001476	63.53	gold quality
nasal cavity mucosa	UBERON:0001826	57.90	gold quality
mucosa of stomach	UBERON:0001199	57.79	gold quality
skeletal muscle tissue	UBERON:0001134	55.71	gold quality
muscle tissue	UBERON:0002385	55.33	gold quality
islet of Langerhans	UBERON:0000006	55.28	gold quality
muscle layer of sigmoid colon	UBERON:0035805	55.06	gold quality
ovary	UBERON:0000992	54.56	gold quality
prostate gland	UBERON:0002367	54.02	gold quality
saliva-secreting gland	UBERON:0001044	52.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	52.09	gold quality
minor salivary gland	UBERON:0001830	51.94	gold quality
left ovary	UBERON:0002119	51.67	gold quality
vastus lateralis	UBERON:0001379	51.34	silver quality
quadriceps femoris	UBERON:0001377	51.09	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.11
E-CURD-112	yes	3.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting C14orf39, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-545-5P	99.66	70.18	2308

Literature-anchored findings (GeneRIF, showing 3)

• Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans. (PMID:33508233)
• Variations of C14ORF39 and SYCE1 Identified in Idiopathic Premature Ovarian Insufficiency and Nonobstructive Azoospermia. (PMID:34718620)
• In silico analysis of a novel pathogenic variant c.7G > A in C14orf39 gene identified by WES in a Pakistani family with azoospermia. (PMID:35305148)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	4930447C04Rik	ENSMUSG00000021098
rattus_norvegicus	Six6os1	ENSRNOG00000031655

Protein

Protein identifiers

Protein SIX6OS1 — Q8N1H7 (reviewed: Q8N1H7)

Alternative names: Six6 opposite strand transcript 1

All UniProt accessions (5): Q8N1H7, G3V257, G3V3U9, G3V493, H0YJQ0

UniProt curated annotations — full annotation on UniProt →

Function. Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination. Required for the appropriate processing of intermediate recombination nodules before crossover formation.

Subunit / interactions. Interacts with SYCE1. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis.

Subcellular location. Chromosome.

Tissue specificity. Highest expression in retina, skeletal muscle, testis and colon.

Disease relevance. Spermatogenic failure 52 (SPGF52) [MIM:619202] An autosomal recessive infertility disorder characterized by azoospermia due to meiotic arrest at the spermatocyte stage. The disease is caused by variants affecting the gene represented in this entry. Premature ovarian failure 18 (POF18) [MIM:619203] A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF18 is an autosomal recessive form characterized by irregular menstrual cycles and cessation of menstruation in the third decade of life. The uterus is small, ovaries may be small or rudimentary, and do not show follicular activity. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_777638* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031380	SIX6OS1	Family

Pfam: PF15676

UniProt features (12 total): sequence variant 4, region of interest 2, sequence conflict 2, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N1H7-F1	58.97	0.29

Functional residue map

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

Post-translational modifications (1): 439

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, chr14q23, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS

GO Biological Process (9): homologous chromosome pairing at meiosis (GO:0007129), synaptonemal complex assembly (GO:0007130), spermatogenesis (GO:0007283), meiotic DNA double-strand break processing involved in reciprocal meiotic recombination (GO:0010705), oogenesis (GO:0048477), obsolete regulation of DNA-binding transcription factor activity (GO:0051090), DNA recombination (GO:0006310), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): central element (GO:0000801), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromosome organization involved in meiotic cell cycle	2
homologous chromosome segregation	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
synaptonemal complex organization	1
developmental process involved in reproduction	1
male gamete generation	1
meiotic DNA double-strand break processing	1
reciprocal meiotic recombination	1
germ cell development	1
female gamete generation	1
DNA metabolic process	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
binding	1
synaptonemal complex	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C14orf39	SYCE2	Q6PIF2	886
C14orf39	TEX12	Q9BXU0	866
C14orf39	SYCE1	Q8N0S2	863
C14orf39	SYCE3	A1L190	822
C14orf39	SYCP1	Q15431	822
C14orf39	SYCP3	Q8IZU3	598
C14orf39	RNF212	Q495C1	582
C14orf39	MEIOB	Q8N635	545
C14orf39	SYCP2	Q9BX26	544
C14orf39	HORMAD1	Q86X24	521
C14orf39	MSH4	O15457	498
C14orf39	TERB1	Q8NA31	479
C14orf39	HSF2BP	O75031	476
C14orf39	RAD21L1	Q9H4I0	465
C14orf39	SHOC1	Q5VXU9	461

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MT1X	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.560
TEAD2	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.560
SIX6OS1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000
MT1X	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000
HPGDS	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000
TEAD2	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): C14orf39 (Negative Genetic), C14orf39 (Two-hybrid), C14orf39 (Two-hybrid), MT1X (Two-hybrid), PSMA8 (Affinity Capture-Western), C14orf39 (Two-hybrid), C14orf39 (Cross-Linking-MS (XL-MS)), C14orf39 (Co-fractionation)

ESM2 similar proteins: A1L2H3, A2AKX3, A5D8S0, B0S6S9, D3Z987, E1BC15, O43303, O60673, O95405, P56715, Q03188, Q2M2Z5, Q3MHH3, Q3V089, Q569L8, Q5BQN8, Q5CZC0, Q5DTT3, Q5R9I1, Q5VWN6, Q61493, Q641I1, Q6NS59, Q6NSW3, Q6ZP01, Q6ZU52, Q7TSH4, Q7Z333, Q7Z3T8, Q80U44, Q80U59, Q86UW6, Q86WS4, Q86XD8, Q8IXS0, Q8MJ03, Q8MJ04, Q8MJ06, Q8N1H7, Q8N7Z5

Diamond homologs: Q8N1H7, Q9CTN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	6
Uncertain significance	80
Likely benign	57
Benign	6

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
189378	NM_007374.3(SIX6):c.110T>C (p.Leu37Pro)	Pathogenic
3390936	NM_174978.3(C14orf39):c.139_142del (p.Thr47fs)	Pathogenic
4796756	NM_174978.3(C14orf39):c.508C>T (p.Arg170Ter)	Pathogenic
4796757	NM_174978.3(C14orf39):c.135_136del (p.Lys45fs)	Pathogenic
4796758	C14ORF39, 2-BP DEL, NT325	Pathogenic
4796759	NM_174978.3(C14orf39):c.1349del (p.Pro450fs)	Pathogenic
4796760	NM_174978.3(C14orf39):c.1154_1157del (p.Val385fs)	Pathogenic
637058	NM_007374.3(SIX6):c.547G>C (p.Asp183His)	Pathogenic
637953	NM_007374.3(SIX6):c.-227_572+235del	Pathogenic
992822	NM_174978.3(C14orf39):c.204_205del (p.His68fs)	Pathogenic
992823	NM_174978.3(C14orf39):c.958G>T (p.Glu320Ter)	Pathogenic
992824	NM_174978.3(C14orf39):c.1180-3C>G	Pathogenic
1690892	NM_007374.3(SIX6):c.380del (p.Asp127fs)	Likely pathogenic
189377	NM_007374.3(SIX6):c.532_536del (p.Asn178fs)	Likely pathogenic
2582921	NM_007374.3(SIX6):c.105G>A (p.Trp35Ter)	Likely pathogenic
3776768	NM_007374.3(SIX6):c.433G>T (p.Glu145Ter)	Likely pathogenic
3899291	NM_174978.3(C14orf39):c.207_210del (p.Ser69fs)	Likely pathogenic
870595	NM_007374.3(SIX6):c.549C>G (p.Asp183Glu)	Likely pathogenic

SpliceAI

2861 predictions. Top by Δscore:

Variant	Effect	Δscore
14:60455146:C:CC	acceptor_gain	1.0000
14:60468441:ATAC:A	donor_gain	1.0000
14:60468532:ATCTG:A	acceptor_gain	1.0000
14:60468533:TCTG:T	acceptor_loss	1.0000
14:60468534:CTG:C	acceptor_gain	1.0000
14:60468535:TG:T	acceptor_gain	1.0000
14:60468535:TGCT:T	acceptor_loss	1.0000
14:60468536:GC:G	acceptor_loss	1.0000
14:60468537:C:A	acceptor_loss	1.0000
14:60468537:C:CC	acceptor_gain	1.0000
14:60468538:T:G	acceptor_loss	1.0000
14:60468546:CAAT:C	acceptor_gain	1.0000
14:60468549:T:C	acceptor_gain	1.0000
14:60468549:T:TC	acceptor_gain	1.0000
14:60471738:CT:C	acceptor_gain	1.0000
14:60478294:CTATA:C	donor_gain	1.0000
14:60478298:A:AC	donor_gain	1.0000
14:60478299:C:CC	donor_gain	1.0000
14:60478299:CTTGT:C	donor_gain	1.0000
14:60478317:T:TA	donor_gain	1.0000
14:60483682:AATAC:A	donor_loss	1.0000
14:60483683:ATACT:A	donor_loss	1.0000
14:60483684:TACT:T	donor_loss	1.0000
14:60483685:AC:A	donor_loss	1.0000
14:60483686:CT:C	donor_loss	1.0000
14:60483687:T:TC	donor_loss	1.0000
14:60483688:CACTT:C	donor_loss	1.0000
14:60483689:A:AC	donor_gain	1.0000
14:60483690:C:CT	donor_gain	1.0000
14:60483690:C:T	donor_loss	1.0000

AlphaMissense

3919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:60471430:A:G	W181R	0.990
14:60471430:A:T	W181R	0.990
14:60471428:C:A	W181C	0.976
14:60471428:C:G	W181C	0.976
14:60478388:A:G	W79R	0.975
14:60478388:A:T	W79R	0.975
14:60478386:C:A	W79C	0.968
14:60478386:C:G	W79C	0.968
14:60485041:A:G	L13S	0.958
14:60485044:A:G	L12P	0.956
14:60484933:G:C	F18L	0.954
14:60484933:G:T	F18L	0.954
14:60484935:A:G	F18L	0.954
14:60471446:A:C	F175L	0.945
14:60471446:A:T	F175L	0.945
14:60471448:A:G	F175L	0.945
14:60471429:C:G	W181S	0.941
14:60437004:A:C	F535L	0.940
14:60437004:A:T	F535L	0.940
14:60437006:A:G	F535L	0.940
14:60437010:A:C	F533L	0.929
14:60437010:A:T	F533L	0.929
14:60437012:A:G	F533L	0.929
14:60478366:A:G	F86S	0.928
14:60436938:A:C	F557L	0.923
14:60436938:A:T	F557L	0.923
14:60436940:A:G	F557L	0.923
14:60436944:A:C	F555L	0.923
14:60436944:A:T	F555L	0.923
14:60436946:A:G	F555L	0.923

dbSNP variants (sampled 300 via entrez): RS1000044481 (14:60495700 T>C), RS1000075357 (14:60506597 T>A,G), RS1000100644 (14:60448497 G>T), RS1000142173 (14:60504972 C>A,T), RS1000274959 (14:60442270 T>C,G), RS1000333214 (14:60493534 G>A), RS1000342994 (14:60435492 AAC>A), RS1000349893 (14:60493191 T>G), RS1000396210 (14:60486228 G>A,C), RS1000397921 (14:60483364 C>G,T), RS1000400736 (14:60448220 G>A,C), RS1000415819 (14:60477091 T>C), RS1000421749 (14:60506361 T>C), RS1000430450 (14:60486552 C>T), RS1000506448 (14:60484148 T>G)

Disease associations

OMIM: gene MIM:617307 | disease phenotypes: MIM:212550, MIM:311360, MIM:619202, MIM:619203, MIM:121400, MIM:206900

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 52	Limited	Unknown
premature ovarian failure 18	Limited	Unknown

Mondo (10): colobomatous optic disc-macular atrophy-chorioretinopathy syndrome (MONDO:0008927), inherited primary ovarian failure (MONDO:0019852), spermatogenic failure 52 (MONDO:0030938), premature ovarian failure 18 (MONDO:0030939), pathologic nystagmus (MONDO:0004843), sclerocornea (MONDO:0019629), cornea plana (MONDO:0000733), microphthalmia (MONDO:0021129), anophthalmia/microphthalmia-esophageal atresia syndrome (MONDO:0008799), azoospermia (MONDO:0100459)

Orphanet (6): Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome (Orphanet:435930), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Rare non-acquired premature ovarian failure (Orphanet:95710), Isolated congenital sclerocornea (Orphanet:91490), Congenital cornea plana (Orphanet:53691), Anophthalmia/microphthalmia-esophageal atresia syndrome (Orphanet:77298)

HPO phenotypes

13 total (16 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000027	Azoospermia
HP:0000858	Irregular menstruation
HP:0000869	Secondary amenorrhea
HP:0003251	Male infertility
HP:0008209	Premature ovarian insufficiency
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008724	Hypoplasia of the ovary
HP:0011462	Young adult onset
HP:0011969	Elevated circulating luteinizing hormone level
HP:0025709	Intermediate young adult onset
HP:0031103	Decreased circulating antimullerian hormone circulation
HP:0000647	Sclerocornea
HP:0007720	Flat cornea
HP:0000568	Microphthalmia

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001956_62	Height	8.000000e-13
GCST002647_106	Height	3.000000e-35
GCST003875_13	Gut microbiota (bacterial taxa)	3.000000e-09
GCST003993_25	Menarche (age at onset)	1.000000e-12
GCST006291_59	Spherical equivalent or myopia (age of diagnosis)	8.000000e-11
GCST006395_15	Glaucoma	6.000000e-22
GCST006976_106	Macular thickness	3.000000e-12
GCST006979_1003	Heel bone mineral density	4.000000e-18
GCST007576_184	Chronotype	1.000000e-08
GCST008156_55	Hip circumference adjusted for BMI	4.000000e-06
GCST008163_516	Height	4.000000e-14
GCST009724_57	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-35
GCST011438_8	Glaucoma (primary open-angle)	2.000000e-23
GCST011439_16	Glaucoma (primary open-angle)	7.000000e-28
GCST011440_6	Glaucoma (low intraocular pressure)	1.000000e-24
GCST011441_12	Glaucoma (high intraocular pressure)	5.000000e-14
GCST90020024_772	A body shape index	4.000000e-08
GCST90020028_1862	Hip circumference adjusted for BMI	5.000000e-12
GCST90020028_1866	Hip circumference adjusted for BMI	1.000000e-14

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0004703	age at menarche
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0006939	cup-to-disc ratio measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D053713	Azoospermia	C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380
D008850	Microphthalmos	C11.250.566; C16.131.384.666
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
C565876	Microphthalmia, Isolated, with Cataract 2 (supp.)
C565209	Sclerocornea (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	increases methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT02275169	PHASE3	UNKNOWN	FSH Treatment for Non-obstructive Azoospermic Patients
NCT02544191	PHASE2	UNKNOWN	GnRHa Combined With hCG and hMG for Treatment of Patients With Non-obstructive Azoospermia
NCT03762967	PHASE2	UNKNOWN	Autologous Adipose-Derived Adult Stromal Vascular Cell Administration for Male Patients With Infertility
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT03748732	Not specified	UNKNOWN	Extensive Circumferential Partial Thickness Sclerectomy in Nanophthalmic Eyes
NCT04759560	Not specified	UNKNOWN	Biometric Characteristics of the Eye With Microcornea/Microphthalmia and Congenital Cataract Before And After Cataract Extraction
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children
NCT02041910	PHASE1/PHASE2	UNKNOWN	Testicular Injection of Autologous Stem Cells for Treatment of Patients With Azoospermia
NCT00282477	Not specified	UNKNOWN	Trial to Evaluate Erectile Function, Fertility and Sperm Count in Male Cyclists Compared to Age Matched Controls
NCT00484081	Not specified	COMPLETED	Microdissection Testicular Sperm Extraction (MicroTESE) and IVF-ICSI Outcome in Non-Obstructive Azoospermia (NOA)
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT01375062	Not specified	COMPLETED	Obtaining Undifferentiated Cells From Testis Biopsy
NCT01509482	Not specified	COMPLETED	Insulin Resistance in Idiopathic Oligospermia and Azoospermia
NCT02008799	Not specified	UNKNOWN	Intra Testicular Artery Injection of Bone Marrow Stem Cell in Management of Azoospermia
NCT02339272	Not specified	COMPLETED	Study of Synapsis and Recombination in Male Meiosis and the Implications in Infertility
NCT02414295	Not specified	COMPLETED	Sperm Production in Kleinfelter Syndrome Patients After Mesenchymal Stem Cell Injection
NCT02418832	Not specified	RECRUITING	Testis Needle Aspiration of Sperm in Men With Azoospermia
NCT02617173	Not specified	UNKNOWN	The Effect of Low Electrical Current on Testicular Spermatocyte Count
NCT02773498	Not specified	TERMINATED	Comparison of Medical Results of Testicular Sperm Extraction by Conventional Surgery and Microsurgical Track
NCT03497728	Not specified	TERMINATED	Detection of Microdeletions in the Azoospermia Factor (AZF) Regions in Infertile Male Patients
NCT04675164	Not specified	COMPLETED	Laser Assisted Sperm Selection of Viable Immotile Testicular Sperm in Azoospermic Infertile Men
NCT05479474	Not specified	RECRUITING	Platelet Rich Plasma Testis Treatment for Infertile Men
NCT05628987	Not specified	RECRUITING	The Association of Gut Microbiota and Spermatogenic Dysfunction
NCT05866484	Not specified	COMPLETED	Testicular Sperm Aspiration (TESA) vs. Microfluidic Sperm Separation (MSS)
NCT06524258	Not specified	COMPLETED	Testicular Elastography for Microscopic Testicular Sperm Extraction
NCT06841328	Not specified	RECRUITING	Fertility Enhancement Through Regenerative Treatment in Ovaries and Testes
NCT06941922	Not specified	RECRUITING	Testicular Evaluation of Azoospermia Using Micro-Ultrasound
NCT07074015	Not specified	RECRUITING	IntelliWell: An AI-Assisted Imaging Platform for Detection and Location of Ultra-Rare Testicular Sperm in Surgical Specimens
NCT07357701	Not specified	RECRUITING	Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
NCT07542626	Not specified	RECRUITING	Fertility Restoration With Autografting of Cryopreserved Immature Testicular Tissue