INHBA

Summary

INHBA (inhibin subunit beta A, HGNC:6066) is a protein-coding gene on chromosome 7p14.1, encoding Inhibin beta A chain (P08476). 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 de….

This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. The encoded protein also plays a role in eye, tooth and testis development. Elevated expression of this gene may be associated with cancer cachexia in human patients.

Source: NCBI Gene 3624 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_002192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6066
Approved symbol	INHBA
Name	inhibin subunit beta A
Location	7p14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000122641
Ensembl biotype	protein_coding
OMIM	147290
Entrez	3624

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000242208, ENST00000416150, ENST00000442711, ENST00000464515, ENST00000638023, ENST00000867823, ENST00000916727, ENST00000947876, ENST00000947878, ENST00000947879

RefSeq mRNA: 1 — MANE Select: NM_002192 NM_002192

CCDS: CCDS5464

Canonical transcript exons

ENST00000242208 — 3 exons

Exon	Start	End
ENSE00001410336	41699987	41700517
ENSE00001410976	41703005	41703090
ENSE00001887422	41685114	41690542

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.8551 / max 19154.2608, expressed in 1306 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83754	51.2376	1172
83751	3.5739	895
83753	1.4648	605
83756	0.2234	47
83750	0.2147	96
83752	0.1406	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.40	gold quality
saphenous vein	UBERON:0007318	98.20	gold quality
vena cava	UBERON:0004087	97.92	gold quality
visceral pleura	UBERON:0002401	97.67	gold quality
stromal cell of endometrium	CL:0002255	95.13	gold quality
buccal mucosa cell	CL:0002336	94.41	gold quality
type B pancreatic cell	CL:0000169	93.98	gold quality
islet of Langerhans	UBERON:0000006	92.56	gold quality
placenta	UBERON:0001987	92.16	gold quality
caput epididymis	UBERON:0004358	90.50	gold quality
blood vessel layer	UBERON:0004797	89.99	gold quality
lower lobe of lung	UBERON:0008949	89.35	gold quality
parotid gland	UBERON:0001831	89.20	gold quality
right coronary artery	UBERON:0001625	88.56	gold quality
tendon of biceps brachii	UBERON:0008188	86.78	gold quality
calcaneal tendon	UBERON:0003701	85.46	gold quality
popliteal artery	UBERON:0002250	85.09	gold quality
tibial artery	UBERON:0007610	85.07	gold quality
tendon	UBERON:0000043	84.70	gold quality
gall bladder	UBERON:0002110	84.66	gold quality
aorta	UBERON:0000947	84.47	gold quality
coronary artery	UBERON:0001621	83.86	gold quality
thoracic aorta	UBERON:0001515	83.61	gold quality
ascending aorta	UBERON:0001496	83.52	gold quality
left coronary artery	UBERON:0001626	83.32	gold quality
trabecular bone tissue	UBERON:0002483	83.17	gold quality
decidua	UBERON:0002450	82.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.75	gold quality
periodontal ligament	UBERON:0008266	82.46	gold quality
corpus epididymis	UBERON:0004359	81.97	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-53	yes	3776.10
E-HCAD-15	yes	592.83
E-MTAB-8142	yes	77.93
E-MTAB-8410	yes	43.76
E-ENAD-27	yes	6.29
E-MTAB-6386	no	9.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, EGR1, EOMES, ESR1, ESR2, EVX1, FLCN, FOXH1, FOXL2, GSC, HNF4A, ID1, ID2, ID3, IRX1, LHX3, MITF, MYCN, PITX2, SNAI1, TP53

miRNA regulators (miRDB)

71 targeting INHBA, 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-6867-5P	100.00	82.21	3464
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4672	99.50	71.58	2893

Literature-anchored findings (GeneRIF, showing 40)

• distribution in gestational tissues across human pregnancy and during labour (PMID:11969340)
• Activin was secreted by both endometrial adenocarcinoma cell lines. Activin showed a weak, but significant, mitogenic effect on HEC-50 cells without modifications in Bax and Bcl-2. Activin is a regulator of endometrial cancer cell growth. (PMID:12088879)
• Activin A is potently induced in the bone marrow and may play a role in the suppression of inflammatory or immune processes. (PMID:12149426)
• Activin A promotes human endometrial stromal cell decidualization in vitro. (PMID:12161551)
• Seminal inhibin B levels were higher in normal men than in men after vasectomy and in men with azoospermia. (PMID:12399529)
• synthesis by the endosalpinx (PMID:12414903)
• Activin A induces cardiac ankyrin repeat protein (CARP) in cultured intimal smooth muscle cells in a dose-dependent way. (PMID:12524226)
• 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)
• Activin A promotes Smad2 phosphorylation and its nuclear translocation. As an immediate response to activin A, Smad2 was modified by phosphorylation within 2 hours. (PMID:12665510)
• Activin-A modulates ActRI mRNA levels in human trophoblast cells. (PMID:12702211)
• 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)
• Serum inhibin B is an effective marker of follicular development in infertile women undergoing induction of superovulation, and may represent a further marker for ovarian follicular capacity. (PMID:12877256)
• activin promoted ovine preantral follicle & oocyte growth in vitro, but did not accelerate follicle differentiation; these results support a paracrine role for activin A during early oocyte & follicular development (PMID:14613548)
• Peripheral blood monoCYTES and endothelium, activated by TNFalpha, could be extraplacental sources of activin A in preeclampsia. May have role in mechanisms underlying endothelium dysfunction. (PMID:14671202)
• DLX1 blocks multiple signals from TGF-beta superfamily cytokines such as activin A, TGF-beta1, and BMP-4, including differentiation of a hematopoietic cell line by activin A (PMID:14671321)
• Data indicate that activin A and activin receptors IIA and IIB may be involved in the regulation of germ cell proliferation in the human ovary during the period leading up to primordial follicle formation. (PMID:14738881)
• Activin A markedly increased gene expression of mediators involved in infarction healing and myocardial remodeling in neonatal rat cardiomyocytes. (PMID:14993131)
• the smad pathway and the tumor suppressor menin are key regulators of activin effects on PRL and Pit-1 expression, as well as on cell growth inhibition (PMID:15031321)
• Testosterone secretion is impaired in infants with Klinefelter syndrome. (PMID:15070957)
• Activin A increased the expression of VEGF receptors in cultured sinusoidal endothelial cells. (PMID:15123352)
• activin signaling via type II receptors requires a specific sequence for ALK4 binding (PMID:15123686)
• activin A is a novel stimulus of vascular endothelial growth factor gene expression in hepatocellular carcinoma (PMID:15188178)
• Mutations in INHbetaB and INHbetaA genes are not associated with ovarian failure. (PMID:15205401)
• may be an anabolic factor in cartilage (PMID:15292256)
• Women with POF showed low levels of inhibin A and inhibin B, but not of activin A, whereas the levels of pro-alphaC were significantly higher than in postmenopausal women (PMID:15374731)
• review article of gene expression of inhibin beta A in normal breast carcinoma, fibroadenoma, and normal mammary tissue (PMID:15451571)
• enhanced activin A expression suppresses proliferation and colony formation of human neuroblastoma cell (PMID:15580313)
• activin A inhibits adipogenesis via affecting the transcriptional factor cascade upstream of PPARgamma expression (PMID:15737465)
• Activin A and inhibin A may be used as markers to predict pregnancies that are likely to miscarry. (PMID:15950648)
• Activation of TAK1 (and probably p38-MAPK), but not Smad3, is necessary for triggering induction of oFSHbeta by activin. (PMID:16081641)
• Hyperplastic tissue labelled more intensely than endometrium for the presence of INH-betaA and -betaB. (PMID:16423381)
• When cultured with the mesonephros, Wolffian ducts formed ectopic buds in response to GDNF; inhibition of GDNF-induced budding by activin A led to inhibition of cell proliferation, & decrease of both Pax2 expression and PI3- & MAP kinase phosphorylation (PMID:16643884)
• Activin has autocrine roles in tumor growth of ovarian clear cell adenocarcinoma cells. (PMID:16820918)
• Activin A has opposite effects on glucagon and arx gene expression in alpha-cells compared with beta-cells, a finding that may have relevance during pancreatic endocrine lineage specification and physiological function of the adult islets (PMID:16988001)
• Phosphatidylinositol 3-kinase antagonizes the ability of human embryonic stem cells to differentiate in response to transforming growth factor beta family members such as Activin A (PMID:17204604)
• FGF-2 and activin A enhance their signals each other in bovine aortic endothelial cells, and endogenous activin A is critical for FGF-2-induced capillary formation. (PMID:17384470)
• Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells (PMID:17436000)
• Serum AMH and inhibin B are significantly lower in the men with nonobstructive azoospermia compared to the controls. (PMID:17462637)
• Activin-A is an excellent candidate for an effector molecule in human luteolysis whose paracrine action is inhibited during maternal recognition of pregnancy (PMID:17478557)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inhbaa	ENSDARG00000012671
danio_rerio	inhbab	ENSDARG00000024759
mus_musculus	Inhba	ENSMUSG00000041324
rattus_norvegicus	Inhba	ENSRNOG00000014320

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHA (ENSG00000123999), 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 beta A chain — P08476 (reviewed: P08476)

Alternative names: Activin beta-A chain, Erythroid differentiation protein

All UniProt accessions (2): A4D1W7, P08476

UniProt curated annotations — full annotation on UniProt →

Function. 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. Activin A is a homodimer of INHBA that plays a role in several essential biological processes including embryonic development, stem cell maintenance and differentiation, haematopoiesis, cell proliferation and tissue fibrosis. Signals through type I (such as ACVR1B or ACVR1C) and type II receptors (such as ACVR2A, ACVR2B or BMPR2) which, upon ligand binding, phosphorylate SMAD2 and SMAD3 intracellular signaling mediators that form a complex with SMAD4, translocate to the nucleus and modulate gene expression. Can also activate alternative non-canonical intracellular signaling pathways including the p38 MAPK, extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNKs) to modulate cell migration and differentiation. Alternatively, promotes osteoblastic differentiation via ACVRL1-SMAD1/5/9 pathway. In addition, can engage the type I receptor ACVR1 to form an ACVR1-activin A-type II receptor non-signaling complex (NSC) that renders receptors unavailable for engagement with BMPs, hence resulting in an apparent inhibition of ACVR1-mediated BMP signaling. 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.

Subunit / interactions. Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha/INHA and beta-A/INHBA. Activin A is a homodimer of beta-A/INHBA. Activin AB is a dimer of beta-A/INHBA and beta-B/INHBB. Interacts with FST and FSTL3; these interactions prevent activin A interaction to its type II receptor. Activin A interacts with ACVR2A. Activin A interacts with BMPR2. Inhibin A interacts with ACVR1; this interaction creates a non-signaling complex (NSC) that inhibits ACVR1-mediated BMP signaling. Inhibin A interacts with ACVR2A.

Subcellular location. Secreted.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_002183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000491	Inhibin_betaA	Family
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (50 total): strand 20, helix 10, disulfide bond 5, turn 5, sequence variant 3, signal peptide 1, propeptide 1, sequence conflict 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
9I5W	X-RAY DIFFRACTION	1.77
2ARP	X-RAY DIFFRACTION	2
2ARV	X-RAY DIFFRACTION	2
6Y6N	X-RAY DIFFRACTION	2.03
6Y6O	X-RAY DIFFRACTION	2.04
4MID	X-RAY DIFFRACTION	2.14
1S4Y	X-RAY DIFFRACTION	2.3
5HLY	X-RAY DIFFRACTION	2.3
3B4V	X-RAY DIFFRACTION	2.48
2B0U	X-RAY DIFFRACTION	2.8
5HLZ	X-RAY DIFFRACTION	2.85
1NYS	X-RAY DIFFRACTION	3.05
1NYU	X-RAY DIFFRACTION	3.1
7U5P	X-RAY DIFFRACTION	3.14
7OLY	X-RAY DIFFRACTION	3.27
2P6A	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08476-F1	76.92	0.42

Antibody-complex structures (SAbDab): 1 — 7OLY

Functional residue map

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

Disulfide bonds (5): 390, 314–322, 321–391, 350–423, 354–425

Glycosylation sites (1): 165

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1502540	Signaling by Activin
R-HSA-201451	Signaling by BMP
R-HSA-209822	Glycoprotein hormones
R-HSA-2473224	Antagonism of Activin by Follistatin
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: 643 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, FREAC2_01, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION

GO Biological Process (68): ovarian follicle development (GO:0001541), hair follicle development (GO:0001942), hematopoietic progenitor cell differentiation (GO:0002244), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), autophagy (GO:0006914), defense response (GO:0006952), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), cell-cell signaling (GO:0007267), nervous system development (GO:0007399), androgen metabolic process (GO:0008209), negative regulation of cell population proliferation (GO:0008285), male gonad development (GO:0008584), positive regulation of gene expression (GO:0010628), cytokine-mediated signaling pathway (GO:0019221), striatal medium spiny neuron differentiation (GO:0021773), cell differentiation (GO:0030154), erythrocyte differentiation (GO:0030218), negative regulation of cell growth (GO:0030308), negative regulation of type II interferon production (GO:0032689), activin receptor signaling pathway (GO:0032924), positive regulation of collagen biosynthetic process (GO:0032967), endodermal cell differentiation (GO:0035987), negative regulation of phosphorylation (GO:0042326), odontogenesis (GO:0042476), hemoglobin biosynthetic process (GO:0042541), progesterone secretion (GO:0042701), negative regulation of B cell differentiation (GO:0045578), positive regulation of erythrocyte differentiation (GO:0045648), negative regulation of macrophage differentiation (GO:0045650), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), regulation of follicle-stimulating hormone secretion (GO:0046880), positive regulation of follicle-stimulating hormone secretion (GO:0046881), negative regulation of follicle-stimulating hormone secretion (GO:0046882), mesodermal cell differentiation (GO:0048333), positive regulation of protein metabolic process (GO:0051247), Sertoli cell differentiation (GO:0060008)

GO Molecular Function (9): cytokine activity (GO:0005125), hormone activity (GO:0005179), growth factor activity (GO:0008083), peptide hormone binding (GO:0017046), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), type II activin receptor binding (GO:0070699), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), activin A complex (GO:0043509), inhibin A complex (GO:0043512), perinuclear region of cytoplasm (GO:0048471), enzyme activator complex (GO:0150005)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by TGFB family members	3
Peptide hormone biosynthesis	1
Signaling by Activin	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
receptor ligand activity	3
anatomical structure development	2
negative regulation of cellular process	2
protein binding	2
binding	2
cellular anatomical structure	2
female gonad development	1
hair cycle process	1
skin epidermis development	1
hemopoiesis	1
cell differentiation	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
response to stress	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
cell communication	1
signaling	1
system development	1
steroid metabolic process	1
hormone metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
gonad development	1
development of primary male sexual characteristics	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
striatum development	1
forebrain neuron differentiation	1
GABAergic neuron differentiation	1
cellular developmental process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1

Protein interactions and networks

STRING

2146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INHBA	ACVR2A	P27037	980
INHBA	ACVR2B	Q13705	904
INHBA	FST	P19883	899
INHBA	INHBB	P09529	874
INHBA	INHA	P05111	863
INHBA	IGSF1	Q8N6C5	845
INHBA	ACVR1B	P36896	814
INHBA	ACVR1C	Q8NER5	804
INHBA	BMPER	Q8N8U9	712
INHBA	FSTL3	O95633	638
INHBA	SMAD3	P84022	637
INHBA	THBS2	P35442	629
INHBA	SMAD7	O15105	550
INHBA	COL1A2	P02464	549
INHBA	COL3A1	P02461	546

IntAct

37 interactions, top by confidence:

A	B	Type	Score
Fst	INHBA	psi-mi:“MI:0407”(direct interaction)	0.560
INHBA	Fst	psi-mi:“MI:0407”(direct interaction)	0.560
INHBA	AKT1	psi-mi:“MI:0915”(physical association)	0.550
INHBA	AKT1	psi-mi:“MI:2364”(proximity)	0.550
AKT1	INHBA	psi-mi:“MI:0915”(physical association)	0.550
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
INHBA	BRAF	psi-mi:“MI:2364”(proximity)	0.470
INHBA	BRAF	psi-mi:“MI:0915”(physical association)	0.470
INHBA	CFTR	psi-mi:“MI:0915”(physical association)	0.370
GINM1	FAM234B	psi-mi:“MI:0914”(association)	0.350
ACVR2B	INHBA	psi-mi:“MI:0914”(association)	0.350
ADIPOQ	AGRN	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
INHA	MOCS3	psi-mi:“MI:0914”(association)	0.350
LYPD1	ADAM10	psi-mi:“MI:0914”(association)	0.350
PATE1	AGRN	psi-mi:“MI:0914”(association)	0.350
FBXW7	INHBA	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	INHBA	psi-mi:“MI:2364”(proximity)	0.270
INHBA	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	INHBA	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (29): INHBA (Reconstituted Complex), INHBA (Reconstituted Complex), ALDH4A1 (Co-fractionation), LYPLAL1 (Co-fractionation), INHBA (Co-fractionation), IDH2 (Co-fractionation), HMGCL (Co-fractionation), MSRB2 (Co-fractionation), INHBA (Affinity Capture-Western), ACVR2A (Affinity Capture-Western), ACVR2B (Affinity Capture-Western), ACVR1B (Affinity Capture-Western), INHBA (Affinity Capture-MS), INHBA (Affinity Capture-MS), INHBA (Affinity Capture-MS)

ESM2 similar proteins: A4IIK7, A8K855, B5MFE9, D3Z2R5, E7F240, F1QPX0, F1R520, O94985, P03970, P07995, P08476, P10600, P17125, P18331, P23352, P27092, P33005, P43032, P55102, Q04998, Q08761, Q0VCN6, Q15198, Q2PFX1, Q5BIP2, Q5R2I8, Q5R2J4, Q5R9Q9, Q5RJP7, Q66KI8, Q68CR1, Q6DF34, Q6GNK9, Q6PE55, Q6Q0N0, Q6X2S4, Q7T2L7, Q7Z494, Q80TS8, Q8BR86

Diamond homologs: A8E7N9, G5EEL5, O08717, O18828, O18830, O19006, O42222, O46564, O46576, O88959, O95390, O95393, O95972, P03970, P07713, P07995, P08476, P09534, P12643, P12644, P12645, P18075, P18331, P20722, P20863, P21274, P21275, P22003, P22004, P22444, P23359, P25703, P27092, P27539, P30884, P30885, P30886, P34820, P34821, P34822

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
FST	“down-regulates activity”	INHBA	binding
INHBA	“up-regulates activity”	ACVR2A	binding
INHBA	“up-regulates activity”	ACVR2B	binding
IRX1	“up-regulates quantity by expression”	INHBA	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	53.9×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

612 predictions. Top by Δscore:

Variant	Effect	Δscore
7:41690350:T:TA	donor_gain	1.0000
7:41690134:T:TA	donor_gain	0.9900
7:41690140:T:TA	donor_gain	0.9900
7:41690157:G:A	donor_gain	0.9900
7:41690363:C:A	donor_gain	0.9900
7:41690561:A:C	acceptor_gain	0.9900
7:41694155:G:C	donor_gain	0.9900
7:41702999:CATTA:C	donor_loss	0.9900
7:41703000:ATTAC:A	donor_loss	0.9900
7:41703001:TTACC:T	donor_loss	0.9900
7:41703002:TA:T	donor_loss	0.9900
7:41703003:A:C	donor_loss	0.9900
7:41703004:C:CT	donor_loss	0.9900
7:41703004:CCTTT:C	donor_gain	0.9900
7:41690362:T:TA	donor_gain	0.9800
7:41690543:C:CA	acceptor_loss	0.9800
7:41690544:T:C	acceptor_loss	0.9800
7:41690549:A:AC	acceptor_gain	0.9800
7:41690549:A:C	acceptor_gain	0.9800
7:41690557:CAGCA:C	acceptor_gain	0.9800
7:41690558:A:T	acceptor_gain	0.9800
7:41690560:C:CT	acceptor_gain	0.9800
7:41690128:T:TA	donor_gain	0.9700
7:41690185:T:A	donor_gain	0.9700
7:41690538:TGTTC:T	acceptor_gain	0.9700
7:41690541:TC:T	acceptor_gain	0.9700
7:41690542:CC:C	acceptor_gain	0.9700
7:41690543:C:CC	acceptor_gain	0.9700
7:41692662:T:TC	acceptor_gain	0.9700
7:41694151:A:C	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000119442 (7:41705435 T>C), RS1000132102 (7:41695521 G>A), RS1000367260 (7:41698452 A>G), RS1000379176 (7:41684826 C>T), RS1000424417 (7:41692266 C>A), RS1000456034 (7:41703897 G>C), RS1000524632 (7:41703573 G>A), RS1000760776 (7:41691096 G>A,C), RS1000913579 (7:41700431 C>A,G,T), RS1001043439 (7:41705934 G>A,T), RS1001102699 (7:41697214 A>G), RS1001114650 (7:41706920 G>T), RS1001426364 (7:41693731 T>C), RS1001639993 (7:41706617 A>G), RS1001765662 (7:41700055 A>C,G)

Disease associations

OMIM: gene MIM:147290 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000880_38	Menarche (age at onset)	6.000000e-14
GCST001897_4	Pit-and-Fissure caries	7.000000e-06
GCST002371_2	Parent of origin effect on language impairment (paternal)	4.000000e-07
GCST002541_59	Menarche (age at onset)	9.000000e-24
GCST003993_37	Menarche (age at onset)	4.000000e-10
GCST004780_6	Cortisol levels (saliva)	1.000000e-06
GCST005212_23	Asthma	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0005843	cortisol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3588735 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2237435	INHBA		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, decreases reaction, increases expression, affects binding (+2 more)	7
Progesterone	affects binding, affects cotreatment, increases secretion, increases expression, decreases expression (+3 more)	6
Valproic Acid	decreases methylation, affects cotreatment, increases expression	6
sodium arsenite	decreases expression, increases expression	5
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	5
Cadmium	increases abundance, increases expression, decreases secretion	4
Asbestos, Crocidolite	increases expression, affects expression, decreases expression	4
Particulate Matter	increases reaction, increases abundance, increases expression, decreases expression, affects expression	4
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases reaction, increases expression, increases phosphorylation, increases secretion, affects cotreatment	3
Acetaminophen	decreases expression, increases expression	3
Oxygen	increases expression, decreases expression	3
Silicon Dioxide	increases expression	3
Nanotubes, Carbon	increases expression, decreases expression	3
methylmercuric chloride	increases expression	2
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	affects cotreatment, decreases expression	2
Arsenic Trioxide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Busulfan	decreases reaction, increases expression	2
Calcitriol	decreases expression, increases expression, decreases reaction	2
Dexamethasone	decreases expression, affects cotreatment	2
Doxorubicin	affects response to substance, affects expression	2
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
8-Bromo Cyclic Adenosine Monophosphate	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3592247	Binding	Inhibition of interaction of activin A (unknown origin)/ActRIIA-ECD complex with ALK4-ECD-Fc after 120 secs by competitive binding/ Blitz binding assay	Virtual High-Throughput Screening To Identify Novel Activin Antagonists. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9KU	Abcam A-549 INHBA KO	Cancer cell line	Male

Clinical trials (associated diseases)

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