INHA

Summary

INHA (inhibin subunit alpha, HGNC:6065) is a protein-coding gene on chromosome 2q35, encoding Inhibin alpha chain (P05111). Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland.

This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate multiple peptide products, including the alpha subunit of the inhibin A and B protein complexes. These complexes negatively regulate follicle stimulating hormone secretion from the pituitary gland. Inhibins have also been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. Mutations in this gene may be associated with male infertility and premature ovarian failure in female human patients.

Source: NCBI Gene 3623 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6065
Approved symbol	INHA
Name	inhibin subunit alpha
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123999
Ensembl biotype	protein_coding
OMIM	147380
Entrez	3623

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000243786, ENST00000489456

RefSeq mRNA: 1 — MANE Select: NM_002191 NM_002191

CCDS: CCDS2444

Canonical transcript exons

ENST00000243786 — 2 exons

Exon	Start	End
ENSE00000843609	219572310	219572642
ENSE00000843610	219574694	219575711

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8256 / max 208.2761, expressed in 156 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25528	0.3448	67
25529	0.1602	70
25525	0.1432	27
25527	0.1288	27
25526	0.0374	14
202578	0.0112	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.42	gold quality
right testis	UBERON:0004534	96.72	gold quality
left testis	UBERON:0004533	96.66	gold quality
right adrenal gland	UBERON:0001233	95.45	gold quality
testis	UBERON:0000473	95.22	gold quality
left ovary	UBERON:0002119	94.36	gold quality
right adrenal gland cortex	UBERON:0035827	94.16	gold quality
left adrenal gland	UBERON:0001234	93.65	gold quality
right ovary	UBERON:0002118	92.78	gold quality
left adrenal gland cortex	UBERON:0035825	92.44	gold quality
adrenal gland	UBERON:0002369	92.42	gold quality
adrenal cortex	UBERON:0001235	91.58	gold quality
ovary	UBERON:0000992	87.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.57	gold quality
right atrium auricular region	UBERON:0006631	80.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.52	gold quality
adult organism	UBERON:0007023	79.75	gold quality
cardiac atrium	UBERON:0002081	78.51	gold quality
placenta	UBERON:0001987	75.96	gold quality
nucleus accumbens	UBERON:0001882	75.91	gold quality
decidua	UBERON:0002450	75.84	silver quality
body of pancreas	UBERON:0001150	75.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.50	gold quality
cerebellar hemisphere	UBERON:0002245	75.41	gold quality
cerebellar cortex	UBERON:0002129	75.20	gold quality
right frontal lobe	UBERON:0002810	73.93	gold quality
adenohypophysis	UBERON:0002196	73.78	gold quality
caudate nucleus	UBERON:0001873	73.08	gold quality
putamen	UBERON:0001874	73.01	gold quality
pituitary gland	UBERON:0000007	72.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1564.29
E-GEOD-134144	yes	628.53
E-ANND-3	no	0.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CTNNB1, DNMT3A, GATA1, GATA4, GATA6, LEF1, NR4A1, NR5A1, NR5A2, SMAD2, SMAD3, TCF7L2, TFAP2A, WT1

miRNA regulators (miRDB)

19 targeting INHA, 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-6127	100.00	66.76	2188
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-22-5P	97.67	68.92	1355

Literature-anchored findings (GeneRIF, showing 40)

• DNA hypermethylation of the inhibin alpha-subunit gene in prostate carcinoma (PMID:11818495)
• Patients affected by premature ovarian failure for the missense mutation (769G–>A transition) in the exon 2 of the INHalpha gene. (PMID:12093833)
• findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage (PMID:12456605)
• To determine which cell types in the testes may produce inhibin B, the localization of the two subunits of inhibin B was examined in adult testicular biopsies with normal spermatogenesis, spermatogenic arrest, or Sertoli cell only tubules. (PMID:12493718)
• Preliminary results show that inhibin A levels are raised in Asian women affected with fetal Down syndrome and sex chromosome abnormality. (PMID:12576745)
• data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels (PMID:12587530)
• Results quantify the relative expression of inhibin alpha, inhibin/activin beta(A), beta(B), beta(C), follistatin, activin receptors and beta-glycan genes in placental tissue of term pre-eclamptic patients. (PMID:12651901)
• results suggest dissociation between major sources of inhibin A and inhibin pro-alpha C in early pregnancy; identified a link between production of pro-alpha C and luteal steroidogenesis and a predominantly feto-placental origin of inhibin A (PMID:12660265)
• estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase while inhibin A and/or B plays a more critical role as the follicular phase progresses (PMID:12679471)
• Mast cell-derived activin A may play an important role in airway remodeling in patients with asthma at least in part by mediating the proliferation of airway smooth muscle cells. (PMID:12682233)
• Proportions of precursor inhibin B and alpha-subunit forms in the circulation are unchanged in men with spermatogenic disorders indicating there is no alteration of the Sertoli cell inhibin secretory pattern. (PMID:12721183)
• significant correlation between arterial and venous levels of inhibin A, inhibin B and activin A was found in umbilical cord artery and vein; findings suggest the placenta is the main source of inhibin B and the fetus of activin A in the umbilical cord (PMID:12857425)
• Molecular analysis of the katG codon 315 and the promoter region of the inhA is a good alternative to diagnose isoniazid resistance in South Kore.a (PMID:14596968)
• role as a marker for pregnancy viability (PMID:14667886)
• Serum inhibin A may be helpful in predicting the failure of pregnancies. (PMID:14967395)
• The INHalpha gene is a strong candidate gene for ovarian failure (PMID:15205401)
• study expands the immunophenotype of granular cell tumor (S100, CD68, protein gene product 9.5, and inhibin-alpha) regardless of location and supports a neural origin (PMID:15214825)
• no variation between the normal subjects and the premature ovarian failure patients; G769A variation of INHalpha is rare in Korea women with POF. (PMID:15227735)
• Activin A and inhibin A appear to be viable candidates as laboratory parameters for detection of pregnancy induced hypertension. (PMID:15236099)
• Women with premature ovarian failure showed low levels of inhibin A (PMID:15374731)
• review article supports the hypothesis that tumor suppressor activities of the inhibin alpha subunit dominate in non-malignant tissue, but its oncogenic activities emerge during tumorigenesis (PMID:15451570)
• Expressed in Sertoli cells in oligozoospermia. (PMID:15551748)
• Ovulatory cycles were characterized by higher FSH and lower inhibin A leveels in hypergonadotropic hypogonadism or premature ovarian failure. (PMID:15562017)
• Inhibin A expressed in primary clear cell renal cell carcinoma (2/16, 13%) and metastatic clear cell renal cell carcinoma (3/5, 60%). (PMID:15578072)
• The lower inhibin alpha and betaglycan expression in endometrial adenocarcinoma suggests that the inhibin action may be disrupted. (PMID:15745937)
• Inhibin A and activin A may be used as markers to predict pregnancies that are likely to miscarry. (PMID:15950648)
• conclude that obese women present less percentage variation of both inhibin A and B during the menstrual cycle, associated with a low frequency of ovulatory cycles (PMID:16048795)
• Discordant pattern of inhibin A and inhibin B during the rat estrous cycle is due to independent populations of antral follicles making inhibin B (small antral follicles) or inhibin A (large antral follicles). (PMID:16195413)
• Inheritance of specific INHA promoter haplotypes predispose to the development of premature ovarian failure. (PMID:16390856)
• 16C>T and 769G>A variants in INHalpha gene may not be associated to premature ovarian failure disease. (PMID:16396934)
• A strong colocalisation of inhibin-alpha and -betaA could be demonstrated in malignant endometrial tissue. (PMID:16423381)
• analysis of inhibin and transforming growth factor beta-binding sites on betaglycan (PMID:16621788)
• Higher levels of inhibin A and B are associated with oocyte presence but not with fertilization rates. (PMID:16650414)
• A significant lower expression of the inhibin-alpha subunit in IUGR extravillous trophoblast compared to normal pregnancies was observed. (PMID:16670820)
• polymorphisms in the INHA gene may have a role in ovarian failure (PMID:16723387)
• dimeric inhibins do not play a central role in the endocrinological imbalance observed in polycystic ovary syndrome (PMID:16758344)
• inhibin A may have a role in development of severe preeclampsia (PMID:16778388)
• The present findings showed that treatment with vaginal estroprogestinic decreases serum inhibin A and inhibin B levels, the follicular diameter. (PMID:16989826)
• The lower expression of follistatin and beta A subunit in women with recurrent miscarriage may imply an altered activity of activin A at the time of decidualization, which may lead to poor pregnancy outcome in the form of miscarriage. (PMID:17074342)
• glycosylation of Asn(302) of the alpha-subunit of inhibin A and B results in a decrease in bioactivity, and the effect on inhibin A, at least, is explained by its reduced affinity to betaglycan (PMID:17272393)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	inha	ENSDARG00000052433
mus_musculus	Inha	ENSMUSG00000032968
rattus_norvegicus	Inha	ENSRNOG00000020097

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Inhibin alpha chain — P05111 (reviewed: P05111)

All UniProt accessions (1): P05111

UniProt curated annotations — full annotation on UniProt →

Function. Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. Inhibin A is a dimer of alpha/INHA and beta-A/INHBA that functions as a feedback regulator in the hypothalamic-pituitary-gonadal (HPG) axis. Inhibits the secretion of FSH from the anterior pituitary gland by acting on pituitary gonadotrope cells. Antagonizes activin A by binding to the proteoglycan, betaglycan, and forming a stable complex with and, thereby, sequestering type II activin receptors while excluding type I receptor. Inhibin B is a dimer of alpha and beta-B that plays a crucial role in the regulation of the reproductive system by inhibiting the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Thereby, maintains reproductive homeostasis in both males and females. Acts as a more potent suppressor of FSH release than inhibin A. Functions as competitive receptor antagonist binding activin type II receptors with high affinity in the presence of the TGF-beta type III coreceptor/TGFBR3L.

Subunit / interactions. Dimeric, linked by one or more disulfide bonds. Activin B is a dimer of alpha and beta-B. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B. Interacts with TGFBR3L; this interaction regulates female fertility.

Subcellular location. Secreted.

Tissue specificity. Originally found in ovary (granulosa cells) and testis (Sertoli cells), but widely distributed in many tissues including brain and placenta. In adrenal cortex expression is limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia. Also found in adrenocortical tumors. Also expressed in prostate epithelium of benign prostatic hyperplasia, in regions of basal cell hyperplasia and in nonmalignant regions of high grade prostate cancer. Only circulating inhibin B is found in male, whereas circulating inhibins A and B are found in female.

Post-translational modifications. Proteolytic processing yields a number of bioactive forms. The 20/23 kDa forms consist solely of the mature alpha chain, the 26/29 kDa forms consist of the most N-terminal propeptide linked through a disulfide bond to the mature alpha chain, the 50/53 kDa forms encompass the entire proprotein. Each type can be furthermore either mono- or diglycosylated, causing the mass difference.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_002182* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017175	Inhibin_asu	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019

UniProt features (23 total): mutagenesis site 5, disulfide bond 4, sequence variant 3, glycosylation site 3, propeptide 2, sequence conflict 2, site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05111-F1	70.80	0.26

Functional residue map

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

Catalytic / active sites (2): 61–62 (cleavage); 232–233 (cleavage)

Disulfide bonds (4): 291–363, 295–365, 327, 262–328

Glycosylation sites (3): 146, 268, 302

Mutagenesis-validated functional residues (5):

Position	Phenotype
56–57	loss of cleavage; when associated with 60-aa-61.
60–61	loss of cleavage; when associated with 55-aa-56.
231–232	loss of cleavage.
268	loss of glycosylation.
302	loss of glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1502540	Signaling by Activin
R-HSA-201451	Signaling by BMP
R-HSA-209822	Glycoprotein hormones
R-HSA-9839406	TGFBR3 regulates activin signaling
R-HSA-162582	Signal Transduction
R-HSA-209952	Peptide hormone biosynthesis
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 249 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, MYOGENIN_Q6, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_B_CELL_ACTIVATION, GCANCTGNY_MYOD_Q6, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_B_CELL_ACTIVATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT

GO Biological Process (22): skeletal system development (GO:0001501), ovarian follicle development (GO:0001541), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), cell-cell signaling (GO:0007267), male gonad development (GO:0008584), cell differentiation (GO:0030154), erythrocyte differentiation (GO:0030218), negative regulation of type II interferon production (GO:0032689), regulation of cell population proliferation (GO:0042127), negative regulation of phosphorylation (GO:0042326), hemoglobin biosynthetic process (GO:0042541), negative regulation of B cell differentiation (GO:0045578), negative regulation of macrophage differentiation (GO:0045650), negative regulation of cell cycle (GO:0045786), positive regulation of follicle-stimulating hormone secretion (GO:0046881), negative regulation of follicle-stimulating hormone secretion (GO:0046882), regulation of cell cycle (GO:0051726), regulation of follicle-stimulating hormone secretion (GO:0046880), system development (GO:0048731), negative regulation of multicellular organismal process (GO:0051241)

GO Molecular Function (7): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), hormone activity (GO:0005179), growth factor activity (GO:0008083), inhibin binding (GO:0034711), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (8): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), inhibin-betaglycan-ActRII complex (GO:0034673), neuronal cell body (GO:0043025), inhibin A complex (GO:0043512), inhibin B complex (GO:0043513)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by TGFB family members	3
Peptide hormone biosynthesis	1
Signaling by TGFBR3	1
Peptide hormone metabolism	1
Metabolism of proteins	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	3
follicle-stimulating hormone secretion	3
receptor ligand activity	3
cellular anatomical structure	3
cell communication	2
signaling	2
cell cycle	2
regulation of follicle-stimulating hormone secretion	2
protein binding	2
binding	2
inhibin complex	2
system development	1
female gonad development	1
anatomical structure development	1
cellular process	1
cellular response to stimulus	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
gonad development	1
development of primary male sexual characteristics	1
cellular developmental process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
negative regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
cell population proliferation	1
phosphorylation	1
regulation of phosphorylation	1
negative regulation of phosphate metabolic process	1
macromolecule biosynthetic process	1
hemoglobin metabolic process	1
B cell differentiation	1
regulation of B cell differentiation	1
negative regulation of lymphocyte differentiation	1
negative regulation of B cell activation	1
negative regulation of myeloid leukocyte differentiation	1
macrophage differentiation	1
regulation of macrophage differentiation	1
negative regulation of cellular process	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INHA	INHBA	P08476	863
INHA	ALPI	P09923	778
INHA	GLIS3	Q8NEA6	746
INHA	INHBB	P09529	736
INHA	BMP15	O95972	719
INHA	ALPP	P05187	688
INHA	TGFBR3	Q03167	673
INHA	SIX5	Q8N196	654
INHA	ACVR1	Q04771	610
INHA	GDF9	O60383	606
INHA	FSHR	P23945	605
INHA	ACVR2B	Q13705	602
INHA	ACVR1B	P36896	593
INHA	HSD3B1	P14060	564
INHA	AMH	P03971	559

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SIAH1	INHA	psi-mi:“MI:0915”(physical association)	0.560
INHA	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
INHA	HSPA5	psi-mi:“MI:0914”(association)	0.530
FAHD1	CLUH	psi-mi:“MI:0914”(association)	0.530
PPP2R3B	INHA	psi-mi:“MI:0915”(physical association)	0.400
INHA	MOCS3	psi-mi:“MI:0914”(association)	0.350
TCF4	INHA	psi-mi:“MI:0914”(association)	0.350
TMEM129	INHA	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): SIAH1 (Two-hybrid), HSPA5 (Affinity Capture-MS), PDIA3 (Affinity Capture-MS), CALR (Affinity Capture-MS), IKBKG (Affinity Capture-MS), SIAH1 (Two-hybrid), PDIA3 (Affinity Capture-MS), CALR (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), IKBKG (Affinity Capture-MS), INHA (Affinity Capture-Western), HSPA5 (Affinity Capture-MS), IKBKG (Affinity Capture-MS), PDIA3 (Affinity Capture-MS), CALR (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: F1QWZ4, O08717, O13048, O19006, O46564, O46576, O77755, O88959, O95393, O95972, P04087, P05111, P07713, P07994, P12643, P12644, P12645, P17490, P20722, P21274, P21275, P22004, P22444, P25703, P30884, P30885, P34820, P34822, P38440, P43031, P49001, P49002, P55101, P55107, P55108, P58166, P91699, P91706, P97737, Q04906

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INHA	down-regulates	TGFBR3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

280 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219574692:A:AG	acceptor_gain	1.0000
2:219574693:G:GG	acceptor_gain	1.0000
2:219570215:CCGTA:C	donor_loss	0.9900
2:219570216:CGTA:C	donor_loss	0.9900
2:219570217:GTA:G	donor_loss	0.9900
2:219570218:TA:T	donor_loss	0.9900
2:219570219:ACC:A	donor_loss	0.9900
2:219570220:CCTT:C	donor_gain	0.9900
2:219574690:GCAG:G	acceptor_loss	0.9900
2:219574691:CAG:C	acceptor_loss	0.9900
2:219574692:AG:A	acceptor_loss	0.9900
2:219574693:GA:G	acceptor_gain	0.9900
2:219574693:GAT:G	acceptor_gain	0.9900
2:219574692:AGAT:A	acceptor_gain	0.9800
2:219574693:GATG:G	acceptor_gain	0.9800
2:219574682:T:TA	acceptor_gain	0.9700
2:219574689:T:A	acceptor_gain	0.9700
2:219572242:G:GT	donor_gain	0.9600
2:219572242:G:T	donor_gain	0.9600
2:219570219:A:AC	donor_gain	0.9500
2:219570220:C:CC	donor_gain	0.9500
2:219572638:CACAG:C	donor_loss	0.9500
2:219572639:ACAGG:A	donor_loss	0.9500
2:219572640:CAG:C	donor_loss	0.9500
2:219572641:AG:A	donor_loss	0.9500
2:219572642:GG:G	donor_loss	0.9500
2:219572643:G:C	donor_loss	0.9500
2:219572644:T:G	donor_loss	0.9500
2:219574693:GATGC:G	acceptor_gain	0.9500
2:219572260:G:T	donor_gain	0.9400

AlphaMissense

2301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219575253:G:C	W276C	0.997
2:219575253:G:T	W276C	0.997
2:219575237:T:G	F271C	0.995
2:219575236:T:C	F271L	0.994
2:219575238:C:A	F271L	0.994
2:219575238:C:G	F271L	0.994
2:219575262:G:C	W279C	0.994
2:219575262:G:T	W279C	0.994
2:219575296:T:A	C291S	0.991
2:219575297:G:A	C291Y	0.991
2:219575297:G:C	C291S	0.991
2:219575298:T:G	C291W	0.990
2:219575209:T:A	C262S	0.989
2:219575210:G:C	C262S	0.989
2:219575444:T:A	V340D	0.989
2:219574953:G:C	W176C	0.987
2:219574953:G:T	W176C	0.987
2:219575065:T:C	F214L	0.987
2:219575067:C:A	F214L	0.987
2:219575067:C:G	F214L	0.987
2:219575251:T:A	W276R	0.987
2:219575251:T:C	W276R	0.987
2:219574769:T:G	F115C	0.985
2:219575297:G:T	C291F	0.985
2:219575407:T:A	C328S	0.984
2:219575408:G:C	C328S	0.984
2:219575237:T:C	F271S	0.982
2:219575287:T:C	F288L	0.982
2:219575288:T:G	F288C	0.982
2:219575289:C:A	F288L	0.982

dbSNP variants (sampled 300 via entrez): RS1000907726 (2:219571804 C>T), RS1001360087 (2:219571586 C>A,G,T), RS1004353002 (2:219572336 G>A,T), RS1004751360 (2:219571463 G>C), RS1005228764 (2:219571305 G>A,C,T), RS1005355260 (2:219573617 C>A,G,T), RS1005411760 (2:219574532 T>C), RS1006280232 (2:219574643 C>T), RS1007512209 (2:219570696 G>A), RS1007826409 (2:219575424 G>T), RS1008166879 (2:219575782 C>T), RS1008267340 (2:219572115 C>A,G), RS1008508130 (2:219571606 G>A,C,T), RS1008620099 (2:219571110 A>G,T), RS1009287576 (2:219573251 G>A)

Disease associations

OMIM: gene MIM:147380 | 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

0 associations (top):

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: yes

ChEMBL targets (1): CHEMBL5169109 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,097 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL497318	CANNABIGEROL	2	11,097

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.28	IC50	5200	nM	CANNABIGEROL

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentylbenzene-1,3-diol	1845667: Inhibition of Inh (unknown origin)	ic50	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases methylation	2
sodium arsenite	decreases expression	2
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
glycidyl methacrylate	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression, increases reaction	1
Cocaine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dibutyl Phthalate	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	affects expression	1
Fonofos	increases methylation	1
Endosulfan	increases expression	1
Estradiol	decreases expression	1
Flame Retardants	decreases expression	1
Lead	affects expression	1
Parathion	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5096678	Binding	Inhibition of Inh (unknown origin)	Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the “Big Two”. — J Nat Prod

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