DAZL

Summary

DAZL (deleted in azoospermia like, HGNC:2685) is a protein-coding gene on chromosome 3p24.3, encoding Deleted in azoospermia-like (Q92904). RNA-binding protein, which is essential for gametogenesis in both males and females.

The DAZ (Deleted in AZoospermia) gene family encodes potential RNA binding proteins that are expressed in prenatal and postnatal germ cells of males and females. The protein encoded by this gene is localized to the nucleus and cytoplasm of fetal germ cells and to the cytoplasm of developing oocytes. In the testis, this protein is localized to the nucleus of spermatogonia but relocates to the cytoplasm during meiosis where it persists in spermatids and spermatozoa. Transposition and amplification of this autosomal gene during primate evolution gave rise to the DAZ gene cluster on the Y chromosome. Mutations in this gene have been linked to severe spermatogenic failure and infertility in males. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1618 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ovarian failure (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 47 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2685
Approved symbol	DAZL
Name	deleted in azoospermia like
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	DAZH, SPGYLA, MGC26406, DAZL1
Ensembl gene	ENSG00000092345
Ensembl biotype	protein_coding
OMIM	601486
Entrez	1618

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000250863, ENST00000399444, ENST00000454457

RefSeq mRNA: 2 — MANE Select: NM_001351 NM_001190811, NM_001351

CCDS: CCDS43059, CCDS54556

Canonical transcript exons

ENST00000399444 — 11 exons

Exon	Start	End
ENSE00000754034	16593655	16593768
ENSE00000891395	16594533	16594583
ENSE00001538386	16605203	16605423
ENSE00001596931	16598087	16598178
ENSE00001638175	16595314	16595385
ENSE00001702504	16597490	16597541
ENSE00001707692	16598452	16598598
ENSE00001726200	16592050	16592148
ENSE00001741360	16596988	16597051
ENSE00003786252	16596750	16596889
ENSE00003901994	16586792	16588713

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 98.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2239 / max 192.6133, expressed in 13 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41348	0.2042	13
41349	0.0197	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.13	gold quality
secondary oocyte	CL:0000655	97.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.02	gold quality
right testis	UBERON:0004534	93.52	gold quality
left testis	UBERON:0004533	92.67	gold quality
testis	UBERON:0000473	92.03	gold quality
adult organism	UBERON:0007023	91.55	gold quality
sperm	CL:0000019	91.44	gold quality
male germ cell	CL:0000015	90.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.62	gold quality
lower lobe of lung	UBERON:0008949	57.90	silver quality
cranial nerve II	UBERON:0000941	56.83	silver quality
endometrium epithelium	UBERON:0004811	56.64	gold quality
decidua	UBERON:0002450	56.55	gold quality
ileal mucosa	UBERON:0000331	53.48	silver quality
hair follicle	UBERON:0002073	52.73	gold quality
vermiform appendix	UBERON:0001154	51.35	gold quality
metanephros	UBERON:0000081	50.71	gold quality
metanephros cortex	UBERON:0010533	50.50	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.33	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
caecum	UBERON:0001153	49.94	gold quality
vastus lateralis	UBERON:0001379	49.56	gold quality
thymus	UBERON:0002370	49.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
deltoid	UBERON:0001476	49.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting DAZL, 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-574-5P	100.00	66.01	989
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4799-5P	99.82	70.60	2663

Literature-anchored findings (GeneRIF, showing 40)

• role of the autosomal candidate gene DAZLA (Deleted in AZoospermia Like Autosome) in male subfertility (PMID:11499325)
• The DAZL transcript and protein are present in human spermatozoa. (PMID:11872225)
• The distinct expression pattern of DAZL protein in the corpus luteum may play an important role in the regulation of luteal function. (PMID:12029071)
• These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis (PMID:12200456)
• findings provide strong evidence for the role of the autosomal DAZL gene in human spermatogenesis (PMID:12414900)
• DAZ/DAZL protein can form a stable complex with human PUM2. (PMID:12511597)
• Role in spermatogenesis. Decreased DAZ proteins in spermatogenic failure may be due to germ cell loss. Transcription of BOULE, DAZL, and DAZ not altered in degrees of spermatogenic failure. No increase of DAZL or BOULE found in DAZ deletion. (PMID:15066460)
• Data suggest that the T54A polymorphism of deleted-in-azoospermia-like (DAZL) protein might play a role in infertility only in Taiwanese or Asiatic individuals. (PMID:15220464)
• In a Caucasian population, the DAZL SNP (single nucleotide polymorphism) 386 is completely absent and SNP 260 is not associated with spermatogenic failure and therefore does not represent a molecular marker for genetic diagnosis of male infertility. (PMID:15520024)
• PUM2 and DAZL, are capable of binding the same mRNA sequences in the 3’UTR of human SDAD1 mRNA. (PMID:15607425)
• DAZL transcripts are present in the last stages of oocyte maturation, in embryoic cell stems, and throughout the preimplantation development. (PMID:15879466)
• DAZL activates translationally silent mRNAs during germ cell development through the direct recruitment of polyA-binding proteins. (PMID:16001084)
• The Thr54–>Ala polymorphism in exon 3 of DAZL has no major role in Japanese males with azoospermia or oligozoospermia. (PMID:16123080)
• SNPs in the DAZL gene may act jointly to affect common reproductive characteristics in the human population. (PMID:16328470)
• study demonstrates the absence of the A386G (T54A) mutation in Indian subcontinent and two mutations A260G (T12A) and A437G (I71V) are polymorpic… these mutations in the DAZL gene are not associated with male infertility in Indian subcontinent (PMID:16573709)
• Novel missense mutations of DAZL may be associated with age at menopause and/or sperm count and warrant further biochemical and genetic investigation. (PMID:16884537)
• Our results suggest that human amniotic fluid represents a new source for the isolation of human DAZL-, C-kit-, SSEA-4-, and Oct-4-positive stem cells without raising the ethical issues associated with human embryonic research. (PMID:18023443)
• In ovarian extracts a marked increase in expression of DAZL mRNA and protein occurred in the 2nd trimester. (PMID:18088417)
• Follicle-stimulating hormone receptor and DAZL gene polymorphisms do not affect the age of menopause. (PMID:18178196)
• Results suggest that DAZL-expressing (DE)cells, which possess some pluripotent/multipotent characteristics of ES cells express OCT-4 and SOX-2 genes, can be easily isolated from blood. (PMID:19327014)
• expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population (PMID:19342699)
• human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes (PMID:19865085)
• Dazl contributes to the differentiation of embryonic stem cells into germ cells. (PMID:20008336)
• 386A–>G was significantly correlated with sperm count (P<0.0001) and motility (P<0.005) and 584+28c–>t was marginally correlated with sperm morphology. (PMID:20462796)
• These results suggest that incorrect epigenetic marks in germline gene DAZL may be correlated with male gametogenic defects. (PMID:20685756)
• overexpression of VASA and or DAZL, in both embryonic and induced pluripotent stem cells promoted differentiation into primordial germ cells, and maturation and progression through meiosis was enhanced. (PMID:22162380)
• results showed no significant differences in the frequency of DAZL AG (P = 0.58) and MTHFR CT (P = 0.44) between oligozoospermic infertile men and controls (PMID:22329245)
• study identified the core promoter of the DAZL gene; also provided preliminary evidence for the role of a novel SNP of the DAZL gene promoter in spermatogenic failure (PMID:22752612)
• The A260G and A386G polymorphisms of the DAZL gene are not correlated with astheno-teratozoospermia-induced male infertility in the Han Chinese population. (PMID:23678708)
• Abnormal DNA methylation of the DAZL promoter might represent an epigenetic marker of male infertility. (PMID:24015185)
• demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl (PMID:24086306)
• Amniotic fluid-derived stem cells (AFSc) seem to express Nodal, Nanog and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells. (PMID:24459810)
• analysis of T12A and T54A polymorphisms role in the development of male infertility (Meta-Analysis) (PMID:24717865)
• Neither the A260G nor the A386G polymorphism of DAZL appeared to be involved in male infertility. (PMID:25323654)
• DAZL was not expressed either in normal cultures or lesions from cervixes with papillomavirus infections and cervical intraepithelial neoplasia. (PMID:25491317)
• analysis demonstrated that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was correlated to male infertility (PMID:25994644)
• Data suggest that DAZL may be one such factor in human female fertility (PMID:26989066)
• hypermethylation of DAZL and BOULE promoters in human sperm is associated with human infertility (PMID:27358391)
• data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo (PMID:27768780)
• Through the translational regulation of novel RNA targets SMC1B and TEX11, DAZL may have a key role in regulating chromosome cohesion and DNA recombination; two processes fundamental in determining oocyte quality and whose establishment in foetal life may support lifelong fertility. (PMID:28364521)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dazl	ENSDARG00000036214
mus_musculus	Dazl	ENSMUSG00000010592
rattus_norvegicus	Dazl	ENSRNOG00000023474
drosophila_melanogaster	bol	FBGN0011206
caenorhabditis_elegans		WBGENE00000935

Paralogs (5): BOLL (ENSG00000152430), DAZ3 (ENSG00000187191), DAZ1 (ENSG00000188120), DAZ4 (ENSG00000205916), DAZ2 (ENSG00000205944)

Protein

Protein identifiers

Deleted in azoospermia-like — Q92904 (reviewed: Q92904)

Alternative names: DAZ homolog, DAZ-like autosomal, Deleted in azoospermia-like 1, SPGY-like-autosomal

All UniProt accessions (3): Q92904, A0A140VK77, E7EV40

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein, which is essential for gametogenesis in both males and females. Plays a central role during spermatogenesis. Acts by binding to the 3’-UTR of mRNA, specifically recognizing GUU triplets, and thereby regulating the translation of key transcripts.

Subunit / interactions. Homodimer and heterodimer. Multiple DAZL RRMs can bind to a single RNA containing multiple GUU triplets. Forms a heterodimer with DAZ. Interacts with BOLL, DAZAP1 and DAZAP2. Interacts with PUM2.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis specific.

Domain organisation. The DAZ domain mediates the interaction with DAZAP1 and DAZAP2.

Similarity. Belongs to the RRM DAZ family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92904-1	1	yes
Q92904-2	2

RefSeq proteins (2): NP_001177740, NP_001342* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR037551	DAZ_RRM_vert	Domain
IPR043628	DAZ_dom	Domain

Pfam: PF00076, PF18872

UniProt features (14 total): sequence variant 3, domain 2, sequence conflict 2, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92904-F1	57.38	0.23

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): 276

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, USF_C, MORF_RAD51L3, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION

GO Biological Process (9): oocyte maturation (GO:0001556), female meiosis II (GO:0007147), germ cell development (GO:0007281), spermatogenesis (GO:0007283), positive regulation of meiotic nuclear division (GO:0045836), positive regulation of translational initiation (GO:0045948), 3’-UTR-mediated mRNA stabilization (GO:0070935), regulation of translation (GO:0006417), cell differentiation (GO:0030154)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), translation activator activity (GO:0008494), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), ribosome (GO:0005840), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	3
positive regulation of translation	2
binding	2
cell maturation	1
oocyte development	1
meiosis II	1
female meiotic nuclear division	1
female gamete generation	1
meiotic cell cycle	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
regulation of meiotic nuclear division	1
positive regulation of meiotic cell cycle	1
positive regulation of nuclear division	1
positive regulation of cell cycle process	1
meiotic nuclear division	1
translational initiation	1
regulation of translational initiation	1
mRNA stabilization	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cellular developmental process	1
nucleic acid binding	1
mRNA binding	1
translation regulator activity	1
protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

2503 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAZL	PUM2	Q8TB72	984
DAZL	DAZAP2	Q15038	912
DAZL	DDX4	Q9NQI0	905
DAZL	SYCE1	Q8N0S2	879
DAZL	SYCE2	Q6PIF2	871
DAZL	NANOS3	P60323	853
DAZL	STRA8	Q7Z7C7	847
DAZL	SYCP1	Q15431	827
DAZL	PRDM14	Q9GZV8	807
DAZL	SYCP3	Q8IZU3	806
DAZL	DZIP1	Q86YF9	801
DAZL	NANOS2	P60321	745
DAZL	PIWIL2	Q8TC59	731
DAZL	DPPA3	Q6W0C5	728
DAZL	PUM1	Q14671	723

IntAct

8 interactions, top by confidence:

A	B	Type	Score
DAZ1	DAZL	psi-mi:“MI:0915”(physical association)	0.570
DAZAP1	DAZL	psi-mi:“MI:0915”(physical association)	0.400
DAZAP2	DAZL	psi-mi:“MI:0915”(physical association)	0.400
DAZL	PUM2	psi-mi:“MI:0915”(physical association)	0.370
BOLL	DAZL	psi-mi:“MI:0915”(physical association)	0.370
DAZL	HSPD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): DAZL (Affinity Capture-MS), DAZ1 (Two-hybrid), DAZL (Two-hybrid), DAZL (Reconstituted Complex), AGO1 (Proximity Label-MS), AGO2 (Proximity Label-MS), AGO3 (Proximity Label-MS), ALG13 (Proximity Label-MS), ANKHD1-EIF4EBP3 (Proximity Label-MS), ANKRD17 (Proximity Label-MS), ATXN2 (Proximity Label-MS), ATXN2L (Proximity Label-MS), BICC1 (Proximity Label-MS), CAPRIN1 (Proximity Label-MS), CASC3 (Proximity Label-MS)

ESM2 similar proteins: B0FZN7, B0FZN8, B0FZN9, B0FZP0, B0FZP1, B0FZP2, B0FZP3, F4JYG0, O57437, P11308, P26323, P41157, P81270, Q01543, Q0DKP4, Q14B70, Q21263, Q24207, Q29RS8, Q4R361, Q4V7Y4, Q503H1, Q5ZKW8, Q64368, Q69V10, Q6F2E2, Q6R0H0, Q71RC2, Q75M35, Q76CY5, Q7Z353, Q804A9, Q80YT9, Q8K402, Q8N9W6, Q8W4I9, Q8WP23, Q90837, Q924M5, Q92904

Diamond homologs: A0A0A0LLY1, A0A0D1DWZ5, A1CRM1, A1D4K4, A2A5N3, A2Q848, A3LXL0, A4QUF0, A5DM21, A5DW14, B3DJT0, F1QB54, F4HT49, O01671, O04319, O14102, O17310, O22173, O61374, O64380, O97018, P04147, P0CB38, P0CP46, P0CP47, P0CR16, P0CR17, P11940, P19339, P19683, P20965, P21187, P23246, P29341, P31209, P42731, P48809, P49313, P60047, P60048

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	32
Likely benign	2
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2580169	NM_001351.4(DAZL):c.220dup (p.Asp74fs)	Pathogenic
2580168	NM_001351.4(DAZL):c.197T>A (p.Val66Glu)	Likely pathogenic

SpliceAI

1470 predictions. Top by Δscore:

Variant	Effect	Δscore
3:16592045:CATA:C	donor_loss	1.0000
3:16592047:TA:T	donor_loss	1.0000
3:16592048:ACC:A	donor_loss	1.0000
3:16592049:CCTT:C	donor_loss	1.0000
3:16592146:TTT:T	acceptor_gain	1.0000
3:16592148:TCTGA:T	acceptor_loss	1.0000
3:16592149:CTGAA:C	acceptor_loss	1.0000
3:16592150:T:A	acceptor_loss	1.0000
3:16594547:AGCT:A	donor_gain	1.0000
3:16594548:G:C	donor_gain	1.0000
3:16594585:T:C	acceptor_gain	1.0000
3:16594585:T:TC	acceptor_gain	1.0000
3:16595300:C:CA	donor_gain	1.0000
3:16596748:A:C	donor_loss	1.0000
3:16596887:CAC:C	acceptor_gain	1.0000
3:16596888:ACCT:A	acceptor_loss	1.0000
3:16596889:CCTT:C	acceptor_loss	1.0000
3:16596891:T:G	acceptor_loss	1.0000
3:16596894:T:C	acceptor_gain	1.0000
3:16596894:T:TC	acceptor_gain	1.0000
3:16596902:C:CT	acceptor_gain	1.0000
3:16596982:ACT:A	donor_loss	1.0000
3:16596983:CTC:C	donor_loss	1.0000
3:16596985:CACA:C	donor_loss	1.0000
3:16596986:A:AC	donor_gain	1.0000
3:16596987:C:CC	donor_gain	1.0000
3:16596987:C:G	donor_loss	1.0000
3:16596987:CAT:C	donor_gain	1.0000
3:16596987:CATA:C	donor_gain	1.0000
3:16596987:CATAA:C	donor_gain	1.0000

AlphaMissense

1926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:16597008:G:T	A113E	1.000
3:16597014:C:T	G111D	1.000
3:16597023:A:G	L108P	1.000
3:16597524:A:G	F87S	1.000
3:16597530:A:T	V85D	1.000
3:16597532:A:C	F84L	1.000
3:16597532:A:T	F84L	1.000
3:16597533:A:C	F84C	1.000
3:16597533:A:G	F84S	1.000
3:16597534:A:C	F84V	1.000
3:16597534:A:G	F84L	1.000
3:16597536:C:T	G83E	1.000
3:16597537:C:G	G83R	1.000
3:16597537:C:T	G83R	1.000
3:16597540:A:C	Y82D	1.000
3:16597540:A:G	Y82H	1.000
3:16598087:C:T	G81D	1.000
3:16598089:T:A	K80N	1.000
3:16598089:T:G	K80N	1.000
3:16598090:T:A	K80I	1.000
3:16598091:T:C	K80E	1.000
3:16598114:A:T	I72N	1.000
3:16598138:C:A	G64V	1.000
3:16598468:C:T	G45E	1.000
3:16598471:A:T	V44D	1.000
3:16598473:A:C	F43L	1.000
3:16598473:A:T	F43L	1.000
3:16598474:A:C	F43C	1.000
3:16598474:A:G	F43S	1.000
3:16598475:A:C	F43V	1.000

dbSNP variants (sampled 300 via entrez): RS1000291375 (3:16602929 T>C), RS1000316064 (3:16592218 GA>G), RS1000469581 (3:16599506 A>G), RS1000557643 (3:16587515 GAA>G), RS1000821262 (3:16598326 A>G), RS1001014968 (3:16605938 C>A,G), RS1001029876 (3:16601975 G>A), RS1001105922 (3:16591139 C>A,T), RS1001241428 (3:16604126 T>A), RS1001293894 (3:16603896 A>G,T), RS1001307566 (3:16593215 G>A), RS1001860861 (3:16599240 AATC>A), RS1002072735 (3:16607205 C>A,T), RS1002181176 (3:16605588 C>A,G,T), RS1002259582 (3:16593471 C>A,T)

Disease associations

OMIM: gene MIM:601486 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ovarian failure	Moderate	Autosomal dominant
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (2): primary ovarian failure (MONDO:0005387), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002022_2	Testicular germ cell tumor	1.000000e-08
GCST002855_8	Testicular germ cell tumor	3.000000e-09
GCST003542_179	Night sleep phenotypes	2.000000e-06
GCST004364_18	Intelligence	5.000000e-08
GCST004364_36	Intelligence	5.000000e-08
GCST004635_5	Testicular germ cell tumor	1.000000e-09
GCST004713_15	Testicular germ cell tumor	3.000000e-10
GCST004748_37	Lung cancer	2.000000e-06
GCST006947_42	Feeling fed-up	5.000000e-08
GCST009391_826	Metabolite levels	1.000000e-06
GCST011703_56	Smoking initiation	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009588	feeling “fed-up” measurement
EFO:0006523	symmetrical dimethylarginine measurement
EFO:0005670	smoking initiation

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

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
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Decitabine	increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
bisphenol F	decreases expression	1
methylmercuric chloride	increases expression, decreases expression	1
bisphenol A	decreases expression	1
alpha-naphthoflavone	decreases expression, decreases reaction	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
sodium arsenite	affects methylation	1
tetrabromobisphenol A	decreases 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
bisphenol S	increases methylation	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Phthalic Acids	decreases methylation	1
Tretinoin	decreases expression	1
9,10-Dimethyl-1,2-benzanthracene	decreases expression, affects reaction, decreases reaction	1
Asbestos, Serpentine	decreases methylation	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists