EHF

Summary

EHF (ETS homologous factor, HGNC:3246) is a protein-coding gene on chromosome 11p13, encoding ETS homologous factor (Q9NZC4). Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation.

This gene encodes a protein that belongs to an ETS transcription factor subfamily characterized by epithelial-specific expression (ESEs). The encoded protein acts as a transcriptional repressor and may be involved in epithelial differentiation and carcinogenesis. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26298 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 65 total
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_012153

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3246
Approved symbol	EHF
Name	ETS homologous factor
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	ESE3, ESEJ
Ensembl gene	ENSG00000135373
Ensembl biotype	protein_coding
OMIM	605439
Entrez	26298

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 53 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000257831, ENST00000450654, ENST00000525253, ENST00000527001, ENST00000527935, ENST00000529161, ENST00000529527, ENST00000530286, ENST00000531728, ENST00000531794, ENST00000532302, ENST00000533754, ENST00000907181, ENST00000907182, ENST00000907183, ENST00000907184, ENST00000907185, ENST00000907186, ENST00000907187, ENST00000907188, ENST00000907189, ENST00000907190, ENST00000907191, ENST00000907192, ENST00000907193, ENST00000907194, ENST00000907195, ENST00000907196, ENST00000907197, ENST00000907198, ENST00000907199, ENST00000907200, ENST00000907201, ENST00000907202, ENST00000907203, ENST00000907204, ENST00000907205, ENST00000907206, ENST00000907207, ENST00000907208, ENST00000907209, ENST00000907210, ENST00000907211, ENST00000907212, ENST00000907213, ENST00000907214, ENST00000951052, ENST00000951053, ENST00000951054, ENST00000951055, ENST00000951056, ENST00000951057, ENST00000951058, ENST00000951059, ENST00000951060

RefSeq mRNA: 19 — MANE Select: NM_012153 NM_001206615, NM_001206616, NM_001378041, NM_001378042, NM_001378043, NM_001378044, NM_001378045, NM_001378046, NM_001378047, NM_001378048, NM_001378049, NM_001378050, NM_001378051, NM_001378052, NM_001378053, NM_001378054, NM_001378055, NM_001378056, NM_012153

CCDS: CCDS55752, CCDS55753, CCDS7894

Canonical transcript exons

ENST00000257831 — 9 exons

Exon	Start	End
ENSE00000918417	34658533	34658728
ENSE00000918419	34656908	34656970
ENSE00000918421	34651737	34651805
ENSE00000918425	34649019	34649081
ENSE00000918426	34646439	34646684
ENSE00001217809	34658832	34663288
ENSE00002143286	34621093	34621228
ENSE00003651425	34642628	34642727
ENSE00003784300	34651542	34651610

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.82.

FANTOM5 (CAGE): breadth broad, TPM avg 14.4055 / max 993.5961, expressed in 493 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113728	10.9943	383
113737	1.4452	159
113729	1.2451	189
113738	0.1759	63
113743	0.1332	48
113741	0.0999	40
113732	0.0634	32
113734	0.0585	30
113736	0.0565	23
113731	0.0417	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.82	gold quality
gingival epithelium	UBERON:0001949	99.64	gold quality
seminal vesicle	UBERON:0000998	99.59	gold quality
gingiva	UBERON:0001828	99.59	gold quality
oral cavity	UBERON:0000167	99.57	gold quality
esophagus squamous epithelium	UBERON:0006920	99.53	gold quality
bronchial epithelial cell	CL:0002328	99.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.31	gold quality
epithelium of nasopharynx	UBERON:0001951	99.23	gold quality
nasopharynx	UBERON:0001728	99.21	gold quality
upper leg skin	UBERON:0004262	99.18	gold quality
lower esophagus mucosa	UBERON:0035834	99.15	gold quality
colonic mucosa	UBERON:0000317	99.08	gold quality
mammalian vulva	UBERON:0000997	98.95	gold quality
pharyngeal mucosa	UBERON:0000355	98.93	gold quality
penis	UBERON:0000989	98.85	gold quality
corpus epididymis	UBERON:0004359	98.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.62	gold quality
rectum	UBERON:0001052	98.50	gold quality
skin of hip	UBERON:0001554	98.44	gold quality
caput epididymis	UBERON:0004358	98.44	gold quality
amniotic fluid	UBERON:0000173	98.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.23	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
saliva-secreting gland	UBERON:0001044	97.99	gold quality
tonsil	UBERON:0002372	97.94	gold quality
urethra	UBERON:0000057	97.93	gold quality
right uterine tube	UBERON:0001302	97.76	gold quality
mouth mucosa	UBERON:0003729	97.74	gold quality
minor salivary gland	UBERON:0001830	97.58	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	1338.30
E-MTAB-10855	yes	1092.85
E-MTAB-10885	yes	570.40
E-MTAB-8221	yes	545.40
E-CURD-7	yes	498.98
E-ENAD-21	yes	497.27
E-MTAB-10287	yes	300.37
E-GEOD-125970	yes	41.83
E-HCAD-10	yes	15.59
E-HCAD-1	yes	15.33
E-MTAB-5061	yes	10.59
E-GEOD-81608	yes	9.54
E-MTAB-6678	yes	9.39
E-GEOD-130148	yes	6.16
E-ENAD-27	yes	4.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
CASP3
CDKN2A
COL2A1
DCDC2	Repression
HLA-DRB1
IL1B
IL6	Activation
LYZ
MAPK1
MMP1	Repression
RUVBL1	Activation
SPRR1B	Activation
TNFRSF10B	Activation

JASPAR motifs

Motif	Name	Family
MA0598.1	EHF	Ets-related
MA0598.2	EHF	Ets-related
MA0598.3	EHF	Ets-related
MA0598.4	EHF	Ets-related

JASPAR matrix evidence (PMIDs): PMID:20378718, PMID:11259407

Upstream regulators (CollecTRI, top): ELF3, NFKB

miRNA regulators (miRDB)

158 targeting EHF, 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-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 33)

• Overexpression of ESE-3 protein in human bronchial smooth muscle cells inhibits MMP-1 promoter activity, suggesting that ESE-3 may function as a transcriptional repressor. (PMID:12444029)
• In addition, we show the possible involvement of co-factors CBP and p300 in ESE-3-mediated DR-5 up-regulation. (PMID:17027647)
• Aberrant expression of EHF and the subsequent disruption of p27-mediated senescence and telomerase activity is likely to contribute significantly to tumor progression. EHF might be a promising target for future cancer therapeutics. (PMID:17172423)
• ESE-3 plays a role in the induction of cellular senescence as a downstream molecule of stress-induced mitogen-activated protein kinase p38. (PMID:17627613)
• Implicated as a candidate tumor suppressor in prostate cancer; decreased expression may result in loss of important regulatory mechanisms in prostate epithelial cells. (PMID:18037958)
• ESE-1 and ESE-3 play an important role in airway inflammation. (PMID:18475289)
• These results indicate that EHF-mediated RUVBL1 expression allows colon tumour cells to avoid p53-mediated apoptosis. (PMID:21617703)
• EHF mRNA levels differentiate ovarian carcinoma from malignant mesothelioma. EHF may be a novel prognostic marker in ovarian carcinoma. (PMID:21855111)
• Low ESE3/EHF expression was also associated with increased biochemical recurrence of prostate cancer and reduced overall survival after prostatectomy (PMID:22505649)
• ESE-3b is the functionally most important ESE-3 isoform in dendritic cells (PMID:23185370)
• The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model. (PMID:23439650)
• EHF modifies the CF phenotype by altering capabilities of the epithelial cell to correctly process the folding and trafficking of mutant p.Phe508del-CFTR. (PMID:24105369)
• Results suggest PPAR-gamma to be involved in the regulation of ESE-3b expression during monocyte-derived dendritic cells (moDCs) development and that ESE-3 expression is not correlated with the immunogenicity of dendritic cells (DCs). (PMID:24219556)
• This study suggests that ESE3 plays an important role in the carcinogenesis of Esophageal Squamous Cell Carcinoma through changes in subcellular localization and may act as a tumor suppressor gene in Esophageal Squamous Cell Carcinoma. (PMID:25950810)
• Results found that EHF was elevated in ovarian cancer tissues and correlated with short survival. Its overexpression in ovarian cancer cells promoted cell growth and metastasis, and inhibited cell apoptosis. (PMID:26258986)
• tight control by ESE3/EHF over the Lin28/let-7 axis is a critical barrier to malignant transformation. (PMID:27197175)
• EHF is a novel functional oncogene in thyroid cancer by transcriptionally regulating HER2 and HER3, and may represent a potential therapeutic target for this cancer (PMID:27517321)
• Human prostate tumors with IL-6 elevation and loss of ESE3/EHF were associated with STAT3 activation and displayed upregulation of genes related to cell adhesion, cancer stem-like and metastatic spread. (PMID:27732936)
• is a novel functional oncogene in gastric cancer by regulating the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. (PMID:27787520)
• ESE3 as a negative regulator of pancreatic ductal adenocarcinomas (PDAC) progression and metastasis by enforcing E-cadherin upregulation. (PMID:27923832)
• EHF activates expression of the SAM pointed domain-containing ETS transcription factor, which contributes to goblet cell hyperplasia. (PMID:28461336)
• The role of EHF in modifying Cystic Fibrosis lung disease severity. (PMID:28549169)
• Tumoral EHF expression associates with the immune profile in human pancreatic ductal adenocarcinoma patients.EHF suppressed the transcription of TGFB1 and CSF2 by directly binding to their promoters. (PMID:30733283)
• Targeting a novel miR-365-3p/EHF/KRT16/beta5-integrin/c-Met signaling pathway could improve treatment efficacy in OSCC. (PMID:30782177)
• Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region. (PMID:31557407)
• Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma. (PMID:32347431)
• Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer. (PMID:33414441)
• EHF enhances malignancy by modulating AKT and MAPK/ERK signaling in nonsmall cell lung cancer cells. (PMID:33907840)
• Activation of EHF via STAT3 phosphorylation by LMP2A in Epstein-Barr virus-positive gastric cancer. (PMID:34014591)
• Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1. (PMID:34452885)
• Pancreatic cancer cell-derived microRNA-155-5p-containing extracellular vesicles promote immune evasion by triggering EHF-dependent activation of Akt/NF-kappaB signaling pathway. (PMID:34482266)
• Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis. (PMID:38781975)
• ETS homologous factor, controlled by lysine-specific demethylase 5B, suppresses clear cell renal cell carcinoma by inducing Filamin-B. (PMID:38880187)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ehf	ENSDARG00000052115
mus_musculus	Ehf	ENSMUSG00000012350
rattus_norvegicus	Ehf	ENSRNOG00000007484

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS homologous factor — Q9NZC4 (reviewed: Q9NZC4)

Alternative names: ETS domain-containing transcription factor, Epithelium-specific Ets transcription factor 3

All UniProt accessions (5): Q9NZC4, E9PN75, E9PPS9, E9PQR6, E9PQX0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene.

Subcellular location. Nucleus.

Tissue specificity. Expressed exclusively in tissues with a high content of epithelial cells. Highly expressed in salivary gland, mammary gland, prostate, and lung. Weakly expressed in kidney and colon. Not detected in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, testis, ovary, small intestine or peripheral blood leukocytes.

Domain organisation. The PNT domain acts as a transcriptional activator.

Induction. By IL1B/interleukin-1 beta and TNF in bronchial smooth muscle cells and fibroblasts. By IL10/interleukin-10 and IFNG/IFN-gamma in monocyte-derived dendritic cells.

Similarity. Belongs to the ETS family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NZC4-1	1, ESE-3B	yes
Q9NZC4-2	2, ESE-3A
Q9NZC4-3	3

RefSeq proteins (19): NP_001193544, NP_001193545, NP_001364970, NP_001364971, NP_001364972, NP_001364973, NP_001364974, NP_001364975, NP_001364976, NP_001364977, NP_001364978, NP_001364979, NP_001364980, NP_001364981, NP_001364982, NP_001364983, NP_001364984, NP_001364985, NP_036285* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR003118	Pointed_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR033071	EHF_SAM_Pointed_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178, PF02198

UniProt features (12 total): sequence conflict 4, splice variant 2, chain 1, domain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
10SM	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZC4-F1	69.12	0.30

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 238 (showing top): CREL_01, GOBP_EPITHELIUM_DEVELOPMENT, JAEGER_METASTASIS_DN, AREB6_01, MCBRYAN_TERMINAL_END_BUD_UP, GGGTGGRR_PAX4_03, ONDER_CDH1_TARGETS_3_DN, CEBPB_01, NFKB_Q6, EVI1_05, NFKB_C, CEBP_Q2, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GROSS_HYPOXIA_VIA_ELK3_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), epithelial cell differentiation (GO:0030855), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
cellular developmental process	1
cell differentiation	1
epithelium development	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EHF	APIP	Q96GX9	667
EHF	PDHX	O00330	456
EHF	SRSF1	Q07955	400
EHF	ZNF485	Q8NCK3	383
EHF	SRSF6	Q13247	380
EHF	SRSF2	Q01130	367
EHF	ELMO2	Q96JJ3	353
EHF	SLC4A7	Q9Y6M7	353
EHF	SMURF1	Q9HCE7	350
EHF	ITGA5	P08648	348
EHF	SLA	Q13239	335
EHF	TGFBR2	P37173	320
EHF	ZSCAN2	Q7Z7L9	318
EHF	SMAD9	O15198	315
EHF	SRSF5	Q13243	311

IntAct

8 interactions, top by confidence:

A	B	Type	Score
EHF	KPRP	psi-mi:“MI:0915”(physical association)	0.560
	EHF	psi-mi:“MI:0915”(physical association)	0.540
EHF		psi-mi:“MI:0407”(direct interaction)	0.540
EHF	USP7	psi-mi:“MI:0915”(physical association)	0.400
FRZB	EHF	psi-mi:“MI:0915”(physical association)	0.370
EHF	ARG1	psi-mi:“MI:0914”(association)	0.350
ELF3	EHF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): XRCC6 (Reconstituted Complex), XRCC5 (Reconstituted Complex), XRCC6 (Affinity Capture-Western), XRCC5 (Affinity Capture-Western), CST6 (Affinity Capture-MS), KPRP (Affinity Capture-MS), EHF (Reconstituted Complex), KPRP (Affinity Capture-MS), CST6 (Affinity Capture-MS), ARG1 (Affinity Capture-MS), EHF (Affinity Capture-RNA), EHF (Affinity Capture-MS), KPRP (Affinity Capture-MS), USP7 (Affinity Capture-MS), EHF (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JMR6, A1A4L6, A1YG61, A2T737, O70273, O75747, P01105, P10157, P11308, P13474, P14921, P15036, P15037, P15062, P18755, P19102, P26323, P27577, P41156, P41157, P41212, P57782, P81270, P97360, Q08AW4, Q15052, Q32LN0, Q3SZL0, Q3US16, Q58DT0, Q60641, Q6GPJ8, Q6P3D7, Q7ZYI3, Q8BZ05, Q8C7R7, Q8HWS3, Q8N8B7, Q8NDB2, Q8VDK3

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EHF	“down-regulates quantity by repression”	DCDC2	“transcriptional regulation”
EHF	“up-regulates quantity by expression”	SPRR1B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1339 predictions. Top by Δscore:

Variant	Effect	Δscore
11:34651540:A:AG	acceptor_gain	1.0000
11:34651541:G:GG	acceptor_gain	1.0000
11:34651541:GA:G	acceptor_gain	1.0000
11:34651607:G:GG	donor_gain	1.0000
11:34658528:A:AG	acceptor_gain	1.0000
11:34658529:T:G	acceptor_gain	1.0000
11:34658531:A:AG	acceptor_gain	1.0000
11:34658532:G:GG	acceptor_gain	1.0000
11:34658532:GACCC:G	acceptor_gain	1.0000
11:34658825:GTTAC:G	acceptor_loss	1.0000
11:34658826:TTACA:T	acceptor_loss	1.0000
11:34658827:TACAG:T	acceptor_loss	1.0000
11:34658828:ACAGA:A	acceptor_loss	1.0000
11:34658829:CAGAT:C	acceptor_loss	1.0000
11:34658830:A:AG	acceptor_gain	1.0000
11:34658830:A:T	acceptor_loss	1.0000
11:34658831:G:GG	acceptor_gain	1.0000
11:34621226:GAG:G	donor_gain	0.9900
11:34621227:AGGTA:A	donor_loss	0.9900
11:34621230:T:A	donor_loss	0.9900
11:34646674:G:GT	donor_gain	0.9900
11:34646681:A:T	donor_gain	0.9900
11:34646832:G:GT	donor_gain	0.9900
11:34649018:GGCCA:G	acceptor_gain	0.9900
11:34651536:TTGTA:T	acceptor_loss	0.9900
11:34651538:GTA:G	acceptor_loss	0.9900
11:34651539:TA:T	acceptor_loss	0.9900
11:34651540:A:AC	acceptor_loss	0.9900
11:34651601:AGCAC:A	donor_gain	0.9900
11:34651727:AT:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013954 (11:34639799 A>C), RS1000085621 (11:34639490 T>C), RS1000110567 (11:34637718 C>T), RS1000181091 (11:34650467 T>A,C,G), RS1000273998 (11:34623968 C>T), RS1000355673 (11:34656703 A>G), RS1000365530 (11:34656939 C>G,T), RS1000369631 (11:34645159 T>C), RS1000431120 (11:34657828 A>G), RS1000581512 (11:34662376 T>A), RS1000684983 (11:34650690 A>G), RS1000710334 (11:34655545 C>G), RS1000768471 (11:34648401 G>A), RS1000807383 (11:34619731 T>G), RS1000837101 (11:34620028 T>A,C)

Disease associations

OMIM: gene MIM:605439 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000088_1	Volumetric brain MRI	3.000000e-06
GCST000884_1	Response to antipsychotic treatment	7.000000e-08
GCST001077_1	Cystic fibrosis severity	1.000000e-09
GCST001737_3	Chronic obstructive pulmonary disease-related biomarkers	7.000000e-09
GCST001762_834	Obesity-related traits	4.000000e-06
GCST002069_7	Systemic lupus erythematosus and Systemic sclerosis	4.000000e-06
GCST002463_19	Systemic lupus erythematosus	2.000000e-07
GCST003143_10	Lung disease severity in cystic fibrosis	1.000000e-07
GCST003143_11	Lung disease severity in cystic fibrosis	3.000000e-06
GCST003143_12	Lung disease severity in cystic fibrosis	2.000000e-10
GCST003143_7	Lung disease severity in cystic fibrosis	7.000000e-09
GCST003143_8	Lung disease severity in cystic fibrosis	1.000000e-09
GCST003143_9	Lung disease severity in cystic fibrosis	3.000000e-09
GCST004093_36	Prostate-specific antigen levels	2.000000e-10
GCST006019_35	Gamma glutamyl transferase levels	1.000000e-09
GCST011349_16	Gamma glutamyl transferase levels	2.000000e-08
GCST012291_4	Schizophrenia, bipolar disorder or recurrent major depressive disorder	3.000000e-06
GCST012297_7	Schizophrenia, bipolar disorder or major depressive disorder	2.000000e-06
GCST90013407_35	Liver enzyme levels (gamma-glutamyl transferase)	5.000000e-36

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004868	volumetric brain MRI
EFO:0005080	CC16 measurement
EFO:0004697	estradiol measurement
EFO:0007744	lung disease severity measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004952	disease recurrence

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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs286913	EHF		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	3
arsenite	decreases expression, increases methylation, increases abundance	2
sodium arsenite	decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
3,19-(2-bromobenzylidene)andrographolide	increases expression, decreases response to substance	1
urushiol	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
geraniol	decreases expression	1
lead acetate	decreases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	decreases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	decreases expression	1
perfluorodecanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
antimonite	decreases expression, increases abundance	1
chromium hexavalent ion	increases abundance, increases expression	1
monomethylarsonous acid	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vemurafenib	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Antimony Potassium Tartrate	increases abundance, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1G0	SEES3-1V human EHF, clone1	Embryonic stem cell	Male
CVCL_A1G1	SEES3-1V human EHF, clone2	Embryonic stem cell	Male
CVCL_A1G2	SEES3-1V human EHF, clone3	Embryonic stem cell	Male

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