DIAPH2

Summary

DIAPH2 (diaphanous related formin 2, HGNC:2877) is a protein-coding gene on chromosome Xq21.33, encoding Protein diaphanous homolog 2 (O60879). Could be involved in oogenesis.

The product of this gene belongs to the diaphanous subfamily of the formin homology family of proteins. This gene may play a role in the development and normal function of the ovaries. Defects in this gene have been linked to premature ovarian failure 2. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 1730 — RefSeq curated summary.

At a glance

• Gene–disease (curated): premature ovarian failure 2A (Limited, GenCC)
• Clinical variants (ClinVar): 346 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_006729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2877
Approved symbol	DIAPH2
Name	diaphanous related formin 2
Location	Xq21.33
Locus type	gene with protein product
Status	Approved
Aliases	POF, DIA, POF2, DIA2
Ensembl gene	ENSG00000147202
Ensembl biotype	protein_coding
OMIM	300108
Entrez	1730

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000324765, ENST00000373049

RefSeq mRNA: 2 — MANE Select: NM_006729 NM_006729, NM_007309

CCDS: CCDS14467, CCDS14468

Canonical transcript exons

ENST00000324765 — 27 exons

Exon	Start	End
ENSE00000673299	97114726	97114965
ENSE00000673301	97099694	97099795
ENSE00000673302	97075167	97075261
ENSE00000673303	97072941	97073042
ENSE00001291044	96918509	96918617
ENSE00001291397	96957828	96958148
ENSE00001294364	96912328	96912402
ENSE00001297290	96945527	96945591
ENSE00001298907	96948935	96949039
ENSE00001307197	96912483	96912552
ENSE00001307924	97599253	97604997
ENSE00001310717	96965093	96965207
ENSE00001319230	96881579	96881718
ENSE00001319497	96942018	96942136
ENSE00001325833	96930733	96930843
ENSE00001329256	96916438	96916574
ENSE00001435159	96937233	96937351
ENSE00001435438	96939266	96939382
ENSE00001617272	97429650	97429745
ENSE00001647562	96758154	96758258
ENSE00001651913	96735758	96735790
ENSE00001685643	97247715	97247839
ENSE00001699194	96738586	96738762
ENSE00001764776	97348116	97348280
ENSE00001783804	97383909	97384044
ENSE00002289605	97141665	97141794
ENSE00003845498	96684842	96685190

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 93.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7800 / max 639.9673, expressed in 1722 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196906	16.2512	1708
196905	2.0888	962
196904	0.8185	462
196907	0.3024	98
196908	0.3011	113
196910	0.0180	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.05	gold quality
parietal pleura	UBERON:0002400	91.33	gold quality
bronchial epithelial cell	CL:0002328	90.79	gold quality
pleura	UBERON:0000977	90.56	gold quality
lower lobe of lung	UBERON:0008949	90.24	gold quality
epithelium of bronchus	UBERON:0002031	89.87	gold quality
visceral pleura	UBERON:0002401	89.61	gold quality
bronchus	UBERON:0002185	89.40	gold quality
hair follicle	UBERON:0002073	89.02	gold quality
calcaneal tendon	UBERON:0003701	88.95	gold quality
blood vessel layer	UBERON:0004797	88.29	gold quality
choroid plexus epithelium	UBERON:0003911	87.87	gold quality
tendon	UBERON:0000043	87.74	gold quality
placenta	UBERON:0001987	87.69	gold quality
sperm	CL:0000019	87.51	gold quality
male germ cell	CL:0000015	87.46	gold quality
parotid gland	UBERON:0001831	87.45	gold quality
tendon of biceps brachii	UBERON:0008188	87.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.44	gold quality
vastus lateralis	UBERON:0001379	86.75	gold quality
layer of synovial tissue	UBERON:0007616	86.72	gold quality
monocyte	CL:0000576	86.63	gold quality
cervix squamous epithelium	UBERON:0006922	86.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.59	gold quality
synovial joint	UBERON:0002217	86.45	gold quality
mononuclear cell	CL:0000842	86.39	gold quality
cauda epididymis	UBERON:0004360	86.32	gold quality
skin of hip	UBERON:0001554	86.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.97	gold quality
upper leg skin	UBERON:0004262	85.90	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	33.48
E-HCAD-25	yes	15.59
E-MTAB-9388	yes	13.35
E-CURD-119	yes	10.73
E-ANND-3	yes	8.26
E-MTAB-6386	no	416.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR5A2

miRNA regulators (miRDB)

108 targeting DIAPH2, 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-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3658	99.96	73.87	4379
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
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 13)

• Dia2 plays an important role in formation of lamellipodia. (PMID:18044991)
• Our results indicated that DIAPH2 may be a polygenic pleiotropy for premature ovarian failure (POF) and AMD. (PMID:21386871)
• Long HIV filopodial formation in infected dendritic cells was dependent on the formin diaphanous 2 (Diaph2) (PMID:22685410)
• Dia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. (PMID:23024796)
• In podocytes, INF2 appears to be an important modulator of actin-dependent behaviors that are under the control of Rho/mDia signaling. (PMID:23620398)
• DIAPH2 has been associated with premature ovarian insufficiency, an aging phenotype in humans. (PMID:24037343)
• Dia1, Dia2, and Dia3 are involved in ErbB2-dependent capture of microtubules at the cell leading edge and ErbB2-driven guided migration. (PMID:24403606)
• Data show that diaphanous related formin 1 protein (Dia1) and diaphanous related formin 2 protein (Dia2) facilitated HIV-1-induced microtubule (MT) stabilization and the intracellular motility of virus particles. (PMID:28760985)
• Low DIA2 expression is associated with breast cancer. (PMID:29596520)
• DIAPH2 gene expression was an independent prognostic factors of clinical pregnancy rate and live birth in ICSI pregnancies. (PMID:30593440)
• Low DIAPH2 expression is associated with metastasis of laryngeal squamous cell carcinoma. (PMID:30793164)
• DIAPH2, PTPRD and HIC1 Gene Polymorphisms and Laryngeal Cancer Risk. (PMID:34299935)
• DIAPH2 gene polymorphisms and laryngeal cancer risk in men. (PMID:38844723)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	diaph2	ENSDARG00000076060
mus_musculus	Diaph2	ENSMUSG00000034480
rattus_norvegicus	Diaph2	ENSRNOG00000057826
drosophila_melanogaster	dia	FBGN0011202
drosophila_melanogaster	Frl	FBGN0267795
caenorhabditis_elegans		WBGENE00018976
caenorhabditis_elegans		WBGENE00019030
caenorhabditis_elegans	sydn-1	WBGENE00021473
caenorhabditis_elegans		WBGENE00021698

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

Protein diaphanous homolog 2 — O60879 (reviewed: O60879)

Alternative names: Diaphanous-related formin-2

All UniProt accessions (1): O60879

UniProt curated annotations — full annotation on UniProt →

Function. Could be involved in oogenesis. Involved in the regulation of endosome dynamics. Implicated in a novel signal transduction pathway, in which isoform 3 and CSK are sequentially activated by RHOD to regulate the motility of early endosomes through interactions with the actin cytoskeleton.

Subunit / interactions. Isoform 3 interacts with RHOD in the GTP-bound form.

Subcellular location. Cytoplasm. Cytosol. Early endosome.

Tissue specificity. Expressed in testis, ovary, small intestine, prostate, lung, liver, kidney and leukocytes.

Disease relevance. Premature ovarian failure 2A (POF2A) [MIM:300511] 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 is caused by variants affecting the gene represented in this entry.

Domain organisation. The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family. Diaphanous subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O60879-1	1, DIA-156	yes
O60879-2	2, DIA-12C, DIA2B
O60879-3	3, DIA2C

RefSeq proteins (2): NP_006720, NP_009293 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010472	FH3_dom	Domain
IPR010473	GTPase-bd	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR014767	DAD_dom	Domain
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR044933	DIA_GBD_sf	Homologous_superfamily
IPR051412	Formin_Homology_Diaphanous_sf	Family

Pfam: PF02181, PF06367, PF06371

UniProt features (23 total): compositionally biased region 5, domain 4, region of interest 4, coiled-coil region 3, splice variant 3, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60879-F1	76.09	0.35

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): 1

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9035034	RHOF GTPase cycle
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-9013405	RHOD GTPase cycle

MSigDB gene sets: 213 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_OOGENESIS, GOMF_GTPASE_BINDING, ONKEN_UVEAL_MELANOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, BROWNE_HCMV_INFECTION_24HR_DN, SCHLOSSER_SERUM_RESPONSE_DN, GUO_HEX_TARGETS_UP, GOMF_ACTIN_BINDING, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, FUJII_YBX1_TARGETS_UP

GO Biological Process (6): female gamete generation (GO:0007292), actin filament polymerization (GO:0030041), oogenesis (GO:0048477), cellular component organization (GO:0016043), actin cytoskeleton organization (GO:0030036), cell differentiation (GO:0030154)

GO Molecular Function (3): actin binding (GO:0003779), signaling receptor binding (GO:0005102), small GTPase binding (GO:0031267)

GO Cellular Component (7): nucleolus (GO:0005730), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), actin filament (GO:0005884), cytoplasm (GO:0005737), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	2
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
cellular anatomical structure	2
gamete generation	1
actin polymerization or depolymerization	1
protein polymerization	1
germ cell development	1
female gamete generation	1
cellular component organization or biogenesis	1
cytoskeleton organization	1
actin filament-based process	1
cellular developmental process	1
cytoskeletal protein binding	1
protein binding	1
GTPase binding	1
nuclear lumen	1
intracellular membraneless organelle	1
endosome	1
intracellular membrane-bounded organelle	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1679 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIAPH2	POF1B	Q8WVV4	875
DIAPH2	RHOD	O00212	865
DIAPH2	BMP15	O95972	779
DIAPH2	WDHD1	O75717	762
DIAPH2	FIGLA	Q6QHK4	715
DIAPH2	FMR1	Q06787	711
DIAPH2	FOXL2	P58012	706
DIAPH2	NOBOX	O60393	693
DIAPH2	IDS	P22304	638
DIAPH2	FNBP4	Q8N3X1	579
DIAPH2	CDC42	P21181	573
DIAPH2	WBP4	O75554	555
DIAPH2	BLVRA	P53004	547
DIAPH2	PFN4	Q8NHR9	541
DIAPH2	WASL	O00401	534

IntAct

15 interactions, top by confidence:

A	B	Type	Score
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
DIAPH2	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
lpqN	SOWAHD	psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
ESD	PIKFYVE	psi-mi:“MI:0914”(association)	0.350
PFN1	WASL	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
SOWAHB	DIAPH1	psi-mi:“MI:0914”(association)	0.350
PRMT2	DIAPH2	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DIAPH2		psi-mi:“MI:0915”(physical association)	0.000
CDC42	DIAPH2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (75): DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-MS), DIAPH2 (Affinity Capture-RNA), DIAPH2 (Affinity Capture-MS), TXNDC12 (Co-fractionation), PMPCA (Co-fractionation), OAT (Co-fractionation), DIAPH2 (Affinity Capture-Western), RHOD (Affinity Capture-Western), DIAPH2 (Affinity Capture-MS), DIAPH2 (Proximity Label-MS)

ESM2 similar proteins: A0JM95, A1A4S6, A2A2Y4, A4II46, A4IJ06, A6NI28, B2RQE8, B5DFQ4, F1LVW7, O60879, O60890, O70566, O95267, P0C7A6, P0CAX5, Q02384, Q07889, Q07890, Q08DP6, Q0P4Q4, Q28EC1, Q4V7P7, Q566W7, Q5R6F6, Q5R803, Q5U4T3, Q62245, Q69ZK0, Q6DBW1, Q6DHR3, Q6NTL4, Q6PCS4, Q6Y5D8, Q6ZM89, Q7YQL5, Q7YQL6, Q8AVG0, Q8BHD4, Q8IV61, Q8N9B8

Diamond homologs: A0A1D5P556, A0A8C0TYJ0, A4D2P6, A5PKA5, A8MUH7, B7WN72, G5ECY0, O08774, O14745, O14924, O15085, O60879, P31007, P31016, P70175, P70441, P78352, P97879, Q09506, Q0D5P3, Q0QWG9, Q12959, Q13425, Q15599, Q15700, Q28619, Q28C55, Q3T0X8, Q3UHD6, Q4R6G4, Q5PYH5, Q5PYH6, Q5PYH7, Q5RCF7, Q5T2W1, Q5ZM14, Q61085, Q61235, Q62108, Q62696

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AURKB	up-regulates	DIAPH2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	141
Likely benign	29
Benign	8

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
11622	t(X;12)(q21;p13)	Pathogenic
1330214	Single allele	Pathogenic
1708202	GRCh37/hg19 Xq21.31-22.1(chrX:90868186-99828437)x1	Pathogenic
686268	GRCh37/hg19 Xq21.32-22.1(chrX:92939446-99556731)x1	Pathogenic
549659	NC_000023.11:g.97519547_97572671dup	Likely pathogenic

SpliceAI

5878 predictions. Top by Δscore:

Variant	Effect	Δscore
X:96712665:T:G	donor_gain	1.0000
X:96738577:T:A	acceptor_gain	1.0000
X:96738581:TGCA:T	acceptor_loss	1.0000
X:96738582:GCAGC:G	acceptor_loss	1.0000
X:96738583:CAGC:C	acceptor_loss	1.0000
X:96738584:A:AG	acceptor_gain	1.0000
X:96738584:A:T	acceptor_loss	1.0000
X:96738584:AGC:A	acceptor_gain	1.0000
X:96738584:AGCGT:A	acceptor_gain	1.0000
X:96738585:G:GA	acceptor_gain	1.0000
X:96738585:GC:G	acceptor_gain	1.0000
X:96738585:GCG:G	acceptor_gain	1.0000
X:96738585:GCGT:G	acceptor_gain	1.0000
X:96738585:GCGTG:G	acceptor_gain	1.0000
X:96738733:G:GT	donor_gain	1.0000
X:96738733:G:T	donor_gain	1.0000
X:96738758:TGATG:T	donor_gain	1.0000
X:96738759:GATG:G	donor_gain	1.0000
X:96738759:GATGG:G	donor_gain	1.0000
X:96738760:ATG:A	donor_gain	1.0000
X:96738761:TG:T	donor_gain	1.0000
X:96738761:TGGT:T	donor_loss	1.0000
X:96738762:GG:G	donor_gain	1.0000
X:96738762:GGT:G	donor_loss	1.0000
X:96738763:G:GA	donor_loss	1.0000
X:96738763:G:GG	donor_gain	1.0000
X:96738764:T:A	donor_loss	1.0000
X:96758254:AATCT:A	donor_gain	1.0000
X:96758255:ATCT:A	donor_gain	1.0000
X:96758255:ATCTG:A	donor_loss	1.0000

AlphaMissense

7296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:96881688:T:C	L186P	1.000
X:96912329:T:A	W197R	1.000
X:96912329:T:C	W197R	1.000
X:97429709:T:C	F1069L	1.000
X:97429711:C:A	F1069L	1.000
X:97429711:C:G	F1069L	1.000
X:96758167:T:C	L119P	0.999
X:96758227:T:A	V139D	0.999
X:96912331:G:C	W197C	0.999
X:96912331:G:T	W197C	0.999
X:96912530:T:C	L237P	0.999
X:96916442:G:A	G246E	0.999
X:96930756:T:A	N334K	0.999
X:96930756:T:G	N334K	0.999
X:96930791:G:C	R346P	0.999
X:96948957:G:C	R511P	0.999
X:96948965:G:C	A514P	0.999
X:96958140:T:A	W643R	0.999
X:96958140:T:C	W643R	0.999
X:96965126:T:A	W657R	0.999
X:96965126:T:C	W657R	0.999
X:97073040:T:C	L717P	0.999
X:97099698:T:C	L751P	0.999
X:97114889:T:C	L838P	0.999
X:97114911:C:A	N845K	0.999
X:97114911:C:G	N845K	0.999
X:97383912:G:C	A1005P	0.999
X:97429680:T:C	L1059P	0.999
X:97429688:G:C	A1062P	0.999
X:97429692:T:C	L1063P	0.999

dbSNP variants (sampled 300 via entrez): RS1000001912 (X:97465302 C>T), RS1000005402 (X:97418009 C>T), RS1000009095 (X:97344399 G>T), RS1000010293 (X:97014226 T>C), RS1000012523 (X:97277372 A>G), RS1000012661 (X:97248621 T>C), RS1000013065 (X:97596125 C>A), RS1000017032 (X:96701970 C>G), RS1000022852 (X:96936696 G>T), RS1000029762 (X:97219141 A>G), RS1000034478 (X:96787243 G>A), RS1000042633 (X:96979833 A>G), RS1000045239 (X:97263658 C>T), RS1000059036 (X:96785209 A>G), RS1000066332 (X:97277759 A>G)

Disease associations

OMIM: gene MIM:300108 | disease phenotypes: MIM:300511, MIM:300088

GenCC curated gene-disease

Disease	Classification	Inheritance
premature ovarian failure 2A	Limited	Unknown

Mondo (3): premature ovarian failure 2A (MONDO:0010350), developmental and epileptic encephalopathy, 9 (MONDO:0010246), primary amenorrhea (MONDO:1060208)

Orphanet (2): Female restricted epilepsy with intellectual disability (Orphanet:101039), X-linked intellectual disability-epilepsy syndrome (Orphanet:2076)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000869	Secondary amenorrhea
HP:0001423	X-linked dominant inheritance
HP:0008209	Premature ovarian insufficiency
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0011462	Young adult onset
HP:0011969	Elevated circulating luteinizing hormone level

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564715	Epilepsy, Female-Restricted, with Mental Retardation (supp.)
C564498	Premature Ovarian Failure 2a (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, increases methylation, increases mutagenesis	8
Cisplatin	affects expression, affects cotreatment, decreases expression	4
Valproic Acid	affects expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	increases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases methylation	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
tobacco tar	decreases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	affects methylation	1
nickel sulfate	decreases expression	1
evodiamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice