HFM1

Summary

HFM1 (helicase for meiosis 1, HGNC:20193) is a protein-coding gene on chromosome 1p22.2, encoding Probable ATP-dependent DNA helicase HFM1 (A2PYH4). Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.

The protein encoded by this gene is thought to be an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. Defects in this gene are a cause of premature ovarian failure 9 (POF9).

Source: NCBI Gene 164045 — RefSeq curated summary.

At a glance

• Gene–disease (curated): premature ovarian failure 9 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 243 total — 9 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 7
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001017975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20193
Approved symbol	HFM1
Name	helicase for meiosis 1
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	MER3, FLJ39011, FLJ36760
Ensembl gene	ENSG00000162669
Ensembl biotype	protein_coding
OMIM	615684
Entrez	164045

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000370425, ENST00000427444, ENST00000430465, ENST00000448819, ENST00000455133, ENST00000462405, ENST00000481900, ENST00000488023, ENST00000497520

RefSeq mRNA: 1 — MANE Select: NM_001017975 NM_001017975

CCDS: CCDS30769

Canonical transcript exons

ENST00000370425 — 39 exons

Exon	Start	End
ENSE00001518888	91404798	91404837
ENSE00001601573	91266017	91266107
ENSE00003462717	91313957	91314060
ENSE00003467084	91315815	91315972
ENSE00003482049	91324675	91324766
ENSE00003488294	91396293	91396405
ENSE00003488930	91351549	91351643
ENSE00003488946	91401012	91401109
ENSE00003495290	91380104	91380236
ENSE00003495467	91262481	91262592
ENSE00003497185	91352506	91352651
ENSE00003500078	91385575	91385834
ENSE00003502415	91375358	91375446
ENSE00003507203	91316391	91316476
ENSE00003515149	91276982	91277062
ENSE00003518506	91378025	91378183
ENSE00003522673	91353256	91353299
ENSE00003525253	91274730	91274809
ENSE00003529319	91319293	91319390
ENSE00003533819	91380912	91380982
ENSE00003570124	91322950	91322997
ENSE00003571609	91353051	91353152
ENSE00003575029	91385187	91385234
ENSE00003578533	91260766	91261359
ENSE00003579382	91379063	91379214
ENSE00003589372	91394093	91394402
ENSE00003630074	91323093	91323199
ENSE00003635127	91313349	91313495
ENSE00003654801	91319078	91319209
ENSE00003655348	91343430	91343510
ENSE00003655352	91316101	91316184
ENSE00003664410	91347429	91347476
ENSE00003668297	91262241	91262392
ENSE00003669480	91350738	91350871
ENSE00003672263	91267745	91267855
ENSE00003679305	91375527	91375727
ENSE00003683944	91273712	91273815
ENSE00003684346	91378403	91378480
ENSE00003690581	91276628	91276743

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 87.11.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6147 / max 35.7857, expressed in 295 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13237	0.6147	295

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.76	gold quality
pituitary gland	UBERON:0000007	83.15	gold quality
adenohypophysis	UBERON:0002196	82.95	gold quality
right testis	UBERON:0004534	82.35	gold quality
left testis	UBERON:0004533	81.73	gold quality
ventricular zone	UBERON:0003053	81.31	gold quality
testis	UBERON:0000473	80.75	gold quality
cerebellar hemisphere	UBERON:0002245	77.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.41	gold quality
cerebellar cortex	UBERON:0002129	77.30	gold quality
ganglionic eminence	UBERON:0004023	76.97	gold quality
left ovary	UBERON:0002119	75.80	gold quality
cerebellum	UBERON:0002037	75.21	gold quality
right ovary	UBERON:0002118	74.58	gold quality
cortical plate	UBERON:0005343	73.72	gold quality
ovary	UBERON:0000992	72.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.34	gold quality
calcaneal tendon	UBERON:0003701	71.11	gold quality
left lobe of thyroid gland	UBERON:0001120	70.98	gold quality
right lobe of thyroid gland	UBERON:0001119	70.23	gold quality
thyroid gland	UBERON:0002046	69.88	gold quality
gastrocnemius	UBERON:0001388	69.34	gold quality
muscle of leg	UBERON:0001383	68.84	gold quality
body of uterus	UBERON:0009853	67.68	gold quality
mucosa of stomach	UBERON:0001199	67.21	gold quality
endocervix	UBERON:0000458	65.99	gold quality
left uterine tube	UBERON:0001303	65.82	gold quality
smooth muscle tissue	UBERON:0001135	65.81	gold quality
hypothalamus	UBERON:0001898	65.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	381.57
E-ANND-3	yes	5.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HMGB2, TP53

miRNA regulators (miRDB)

49 targeting HFM1, 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-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-891B	99.59	69.81	1083

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• hHFM1 is the evolutionally conserved putative human DNA helicase, which may function as a modulator for genome integrity in germ-line tissues. (PMID:17286053)
• Exome sequencing of two Chinese sisters with primary ovarian insufficiency and their parents identified a shared compound heterozygous mutation in a meiotic gene, HFM1, which encodes a protein necessary for homologous recombination of chromosomes. (PMID:24597873)
• Data suggest that HFM1 gene might be associated with primary ovarian insufficiency in Chinese population. (PMID:26679638)
• A novel heterozygous missense mutation in HFM1 (c.3470G > A) associated with premature ovarian insufficiency (POI) is in the affected family members and absent in the unaffected family members in China. Results of the minigene assay reveals that the mutation changes the mRNA splicing repertory. (PMID:31279343)
• Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia. (PMID:34429122)
• Identification of a new splice-acceptor mutation in HFM1 and functional analysis through molecular docking in nonobstructive azoospermia. (PMID:35486194)
• Biallelic HFM1 variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees. (PMID:35526155)
• Novel pathogenic splicing variants in helicase for meiosis 1 (HFM1) are associated with diminished ovarian reserve and poor pregnancy outcomes. (PMID:35881270)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hfm1	ENSDARG00000104288
mus_musculus	Hfm1	ENSMUSG00000043410
rattus_norvegicus	Hfm1	ENSRNOG00000023299

Paralogs (8): MTREX (ENSG00000039123), POLQ (ENSG00000051341), ASCC3 (ENSG00000112249), DDX60 (ENSG00000137628), SNRNP200 (ENSG00000144028), HELQ (ENSG00000163312), DDX60L (ENSG00000181381), SKIC2 (ENSG00000204351)

Protein

Protein identifiers

Probable ATP-dependent DNA helicase HFM1 — A2PYH4 (reviewed: A2PYH4)

Alternative names: DNA 3’-5’ helicase HFM1, SEC63 domain-containing protein 1

All UniProt accessions (5): A2PYH4, C9JA44, C9JQ07, C9JQP7, H0Y3X7

UniProt curated annotations — full annotation on UniProt →

Function. Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.

Tissue specificity. Preferentially expressed in testis and ovary.

Disease relevance. Premature ovarian failure 9 (POF9) [MIM:615724] 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. The disease may be caused by variants affecting the gene represented in this entry.

Cofactor. Might have a zinc-finger.

Similarity. Belongs to the helicase family. SKI2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
A2PYH4-1	1	yes
A2PYH4-2	2

RefSeq proteins (1): NP_001017975* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR004179	Sec63-dom	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR052247	Meiotic_Crossover_Helicase	Family
IPR057842	WH_MER3	Domain

Pfam: PF00270, PF00271, PF02889, PF23445

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (21 total): sequence variant 6, domain 3, splice variant 3, sequence conflict 2, region of interest 2, chain 1, zinc finger region 1, short sequence motif 1, compositionally biased region 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2PYH4-F1	65.49	0.34

Functional residue map

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

Ligand- & substrate-binding residues (1): 303–310

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, TTTGTAG_MIR520D, CTAGGAA_MIR384, GOBP_ORGANELLE_FISSION, TGIF_01, TGGNNNNNNKCCAR_UNKNOWN, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, chr1p22, GOBP_MEIOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOBP_DNA_RECOMBINATION, GOMF_3_5_DNA_HELICASE_ACTIVITY, GOMF_ATP_DEPENDENT_ACTIVITY_ACTING_ON_DNA

GO Biological Process (3): resolution of meiotic recombination intermediates (GO:0000712), reciprocal meiotic recombination (GO:0007131), meiotic cell cycle (GO:0051321)

GO Molecular Function (11): nucleic acid binding (GO:0003676), DNA helicase activity (GO:0003678), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), 3’-5’ DNA helicase activity (GO:0043138), nucleotide binding (GO:0000166), helicase activity (GO:0004386), hydrolase activity (GO:0016787), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
catalytic activity	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
binding	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HFM1	MSH4	O15457	981
HFM1	MSH5	O43196	953
HFM1	C1orf146	Q5VVC0	885
HFM1	TEX11	Q8IYF3	866
HFM1	SLC39A1	Q9NY26	849
HFM1	SPO11	Q9Y5K1	811
HFM1	MUS81	Q96NY9	776
HFM1	MLH1	P40692	772
HFM1	MND1	Q9BWT6	772
HFM1	SHOC1	Q5VXU9	738
HFM1	MLH3	P49751	727
HFM1	REC8	O95072	712
HFM1	RAD51	Q06609	710
HFM1	DNA2	P51530	706
HFM1	MCM8	Q9UJA3	693

IntAct

0 interactions, top by confidence:

BioGRID (9): HFM1 (Affinity Capture-RNA), HFM1 (Two-hybrid), HFM1 (Proximity Label-MS), HFM1 (Affinity Capture-RNA), HFM1 (Affinity Capture-MS), RPS27L (Two-hybrid), HFM1 (Cross-Linking-MS (XL-MS)), HFM1 (Cross-Linking-MS (XL-MS)), HFM1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0B7P9G0, A0A131MCZ8, A2PYH4, A3QM97, B4JXX2, B4QZU1, E1BPX4, G5EBX9, O00835, O13768, O14072, O74431, P32639, P36583, P36775, P38329, P39986, P40527, P47047, P53273, P53914, P87115, P91119, P92006, Q07093, Q09769, Q12296, Q21029, Q3UYK3, Q55EJ3, Q67XQ0, Q6BMW3, Q6CNR9, Q6FPE6, Q6P4Q7, Q6ZT07, Q84K47, Q8RY60, Q9BMK9, Q9FKF2

Diamond homologs: A2PYH4, A2RUV5, A8MB76, B0R7Q2, B6DMK2, D3Z4R1, E1BNG3, E7F8F4, E9PZJ8, F1LNJ2, F1LPQ2, F1NTD6, F4JAA5, O48534, O59025, O60072, O75643, P32639, P51979, P53327, Q09475, Q54G57, Q54XN7, Q55CI8, Q5D892, Q5H9U9, Q5JGV6, Q5UYM9, Q6P4T2, Q8N3C0, Q974S1, Q9FNQ1, Q9HMV6, Q9P7T8, Q9SYP1, Q9UT24, Q9V0A9, Q9VUV9, A7IB61, D0KN27

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	8
Uncertain significance	180
Likely benign	24
Benign	7

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1256008	NM_001017975.6(HFM1):c.1978-2A>C	Pathogenic
126428	NM_001017975.6(HFM1):c.1686G>C (p.Arg562Ser)	Pathogenic
126429	NM_001017975.6(HFM1):c.2651T>G (p.Ile884Ser)	Pathogenic
126430	NM_001017975.6(HFM1):c.2206G>A (p.Gly736Ser)	Pathogenic
126431	NM_001017975.6(HFM1):c.3929_3930delinsG (p.Pro1310fs)	Pathogenic
1328943	NM_001017975.6(HFM1):c.3588+1G>A	Pathogenic
1332895	NM_001017975.6(HFM1):c.1355G>A (p.Arg452Gln)	Pathogenic
1332896	NM_001017975.6(HFM1):c.1472T>C (p.Leu491Pro)	Pathogenic
996213	NM_001017975.6(HFM1):c.1905T>A (p.Tyr635Ter)	Pathogenic
1214012	NM_001017975.6(HFM1):c.2410G>T (p.Glu804Ter)	Likely pathogenic
1256009	NM_001017975.6(HFM1):c.1880T>C (p.Val627Ala)	Likely pathogenic
1332985	NM_001017975.6(HFM1):c.2562_2563del (p.Glu856fs)	Likely pathogenic
2440702	NM_001017975.6(HFM1):c.1159-3_1159-2del	Likely pathogenic
2627515	NM_001017975.6(HFM1):c.2T>C (p.Met1Thr)	Likely pathogenic
3779730	NM_001017975.6(HFM1):c.873+2T>C	Likely pathogenic
3779731	NM_001017975.6(HFM1):c.3057_3058del (p.Arg1021fs)	Likely pathogenic
4845705	NM_001017975.6(HFM1):c.3421C>T (p.Arg1141Ter)	Likely pathogenic

SpliceAI

5856 predictions. Top by Δscore:

Variant	Effect	Δscore
1:91261356:CATA:C	acceptor_gain	1.0000
1:91261360:C:CC	acceptor_gain	1.0000
1:91273814:ACC:A	acceptor_loss	1.0000
1:91273815:CCT:C	acceptor_loss	1.0000
1:91273816:C:A	acceptor_loss	1.0000
1:91273818:T:C	acceptor_gain	1.0000
1:91273818:T:TC	acceptor_gain	1.0000
1:91273833:CA:C	acceptor_gain	1.0000
1:91273834:A:C	acceptor_gain	1.0000
1:91276623:CTAA:C	donor_loss	1.0000
1:91276624:TAA:T	donor_loss	1.0000
1:91276625:AAC:A	donor_loss	1.0000
1:91276626:A:AG	donor_loss	1.0000
1:91276627:CCT:C	donor_loss	1.0000
1:91276980:A:AC	donor_gain	1.0000
1:91276981:C:CC	donor_gain	1.0000
1:91276981:CAG:C	donor_gain	1.0000
1:91313491:CCCAA:C	acceptor_gain	1.0000
1:91313492:CCAA:C	acceptor_gain	1.0000
1:91313492:CCAAC:C	acceptor_gain	1.0000
1:91313493:CAA:C	acceptor_gain	1.0000
1:91313493:CAAC:C	acceptor_gain	1.0000
1:91313496:C:CC	acceptor_gain	1.0000
1:91314059:CC:C	acceptor_gain	1.0000
1:91314060:CC:C	acceptor_gain	1.0000
1:91319279:AT:A	donor_gain	1.0000
1:91319292:CAT:C	donor_gain	1.0000
1:91319294:T:TA	donor_gain	1.0000
1:91322956:A:AC	donor_gain	1.0000
1:91322957:C:CC	donor_gain	1.0000

AlphaMissense

9536 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:91319120:A:G	W924R	0.999
1:91319120:A:T	W924R	0.999
1:91319388:A:G	L862P	0.999
1:91351621:A:T	V667D	0.999
1:91352592:A:G	S631P	0.999
1:91352606:A:G	L626P	0.999
1:91352612:G:T	A624D	0.999
1:91375416:C:G	A543P	0.999
1:91375432:C:A	R537S	0.999
1:91375432:C:G	R537S	0.999
1:91375433:C:A	R537M	0.999
1:91375433:C:G	R537T	0.999
1:91375441:A:C	C534W	0.999
1:91375444:A:C	F533L	0.999
1:91375444:A:T	F533L	0.999
1:91375445:A:G	F533S	0.999
1:91375446:A:G	F533L	0.999
1:91375531:A:G	L531P	0.999
1:91378474:A:G	W389R	0.999
1:91378474:A:T	W389R	0.999
1:91319380:C:G	A865P	0.998
1:91322958:T:A	K858N	0.998
1:91322958:T:G	K858N	0.998
1:91323132:A:G	L832P	0.998
1:91350792:A:G	W718R	0.998
1:91350792:A:T	W718R	0.998
1:91351551:G:C	S690R	0.998
1:91351551:G:T	S690R	0.998
1:91351553:T:G	S690R	0.998
1:91352531:A:G	M651T	0.998

dbSNP variants (sampled 300 via entrez): RS1000059385 (1:91363874 T>C,G), RS1000078719 (1:91314882 A>G,T), RS1000098058 (1:91373854 G>A,C), RS1000134486 (1:91336278 T>C), RS1000135452 (1:91290649 G>A,C), RS1000153022 (1:91264016 C>A,T), RS1000172483 (1:91304449 G>A), RS1000221972 (1:91383565 T>A), RS1000267224 (1:91392460 T>A,G), RS1000268928 (1:91304799 T>C), RS1000310295 (1:91266154 G>A), RS1000348479 (1:91342418 C>T), RS1000350686 (1:91294349 T>C), RS1000396435 (1:91342260 AAG>A,AAGAG), RS1000451458 (1:91363656 A>G)

Disease associations

OMIM: gene MIM:615684 | disease phenotypes: MIM:615724, MIM:270960

GenCC curated gene-disease

Disease	Classification	Inheritance
premature ovarian failure 9	Strong	Autosomal recessive
male infertility with azoospermia or oligozoospermia due to single gene mutation	Disputed Evidence	Autosomal recessive

Mondo (4): premature ovarian failure 9 (MONDO:0014322), azoospermia (MONDO:0100459), spermatogenic failure 4 (MONDO:0010052), (MONDO:0018393)

Orphanet (1): Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000141	Amenorrhea
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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003485_4	Response to fenofibrate (HDL cholesterol levels)	3.000000e-06
GCST009391_430	Metabolite levels	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007805	HDL cholesterol change measurement
EFO:0010384	phosphatidylcholine 38:2 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053713	Azoospermia	C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380
C536875	Arrest of spermatogenesis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	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
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Lead	affects expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

29 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
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
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