INHBB

Summary

INHBB (inhibin subunit beta B, HGNC:6067) is a protein-coding gene on chromosome 2q14.2, encoding Inhibin beta B chain (P09529). 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 a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. Polymorphisms near this gene are associated with pre-eclampsia in female human patients.

Source: NCBI Gene 3625 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_002193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6067
Approved symbol	INHBB
Name	inhibin subunit beta B
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163083
Ensembl biotype	protein_coding
OMIM	147390
Entrez	3625

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000295228

RefSeq mRNA: 1 — MANE Select: NM_002193 NM_002193

CCDS: CCDS2132

Canonical transcript exons

ENST00000295228 — 2 exons

Exon	Start	End
ENSE00001071424	120346136	120346636
ENSE00001071426	120349099	120351803

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9087 / max 25.0469, expressed in 343 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22318	0.9087	343

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.14	gold quality
pericardium	UBERON:0002407	96.34	gold quality
ventricular zone	UBERON:0003053	94.02	gold quality
mammary duct	UBERON:0001765	93.05	gold quality
bronchial epithelial cell	CL:0002328	92.00	gold quality
epithelium of mammary gland	UBERON:0003244	92.00	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.86	gold quality
epithelium of bronchus	UBERON:0002031	91.62	gold quality
bronchus	UBERON:0002185	91.09	gold quality
adipose tissue	UBERON:0001013	90.94	gold quality
connective tissue	UBERON:0002384	89.84	gold quality
mammary gland	UBERON:0001911	89.31	gold quality
thoracic mammary gland	UBERON:0005200	89.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.74	silver quality
adipose tissue of abdominal region	UBERON:0007808	88.63	gold quality
omental fat pad	UBERON:0010414	88.48	gold quality
peritoneum	UBERON:0002358	88.43	gold quality
ganglionic eminence	UBERON:0004023	85.78	gold quality
adult organism	UBERON:0007023	84.51	silver quality
hair follicle	UBERON:0002073	84.40	silver quality
left lobe of thyroid gland	UBERON:0001120	83.88	gold quality
skin of leg	UBERON:0001511	83.30	gold quality
thyroid gland	UBERON:0002046	83.18	gold quality
inferior olivary complex	UBERON:0002127	83.06	silver quality
middle frontal gyrus	UBERON:0002702	82.97	gold quality
skin of hip	UBERON:0001554	82.70	gold quality
right lobe of thyroid gland	UBERON:0001119	82.69	gold quality
minor salivary gland	UBERON:0001830	82.53	gold quality
zone of skin	UBERON:0000014	82.46	gold quality
nipple	UBERON:0002030	82.43	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, GATA1

miRNA regulators (miRDB)

133 targeting INHBB, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839

Literature-anchored findings (GeneRIF, showing 40)

• synthesis by the endosalpinx (PMID:12414903)
• 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)
• 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)
• 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)
• Gonads in anorexia nervosa with weight gain have low level of activity. Inhibin B is early marker of gonadal activity, and with weight gain, awakening of the reproductive function is gradual. (PMID:15070953)
• Mutations in INHbetaB and INHbetaA genes are not associated with ovarian failure. (PMID:15205401)
• Inhibin B pubertal surge is prominent signal of gonadal maturation in females as well as in males. Significantly higher in boys than in girls. Review. (PMID:15319819)
• 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)
• The expression of inhibin betaB by Sertoli cells is dependent on the coexistence of spermatogenic activity within these seminiferous tubules and is low in patients with Sertoli cell only syndrome. (PMID:15551748)
• Ovulatory cycles were characterized by higher FSH and lower inhibin B leveels in hypergonadotropic hypogonadism or premature ovarian failure. (PMID:15562017)
• Regular increase of inhibin B(InhB) during puberty. In first phases of gonadal maturation, InhB and FSH correlate positively, while in mid-late stages relationship is inverse. In mid-puberty (G3-G4), serum InhB increases. (PMID:15757857)
• Exposure of the cells of Sertoli to excessive amounts of lead results in inappropriate inhibin B overproduction that may be involved in the impairment of spermatogenesis. (PMID:15910540)
• inhibin B may have a role in male fecundity (PMID:16024538)
• 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)
• Hyperplastic tissue labelled more intensely than endometrium for the presence of INH-betaA and -betaB. (PMID:16423381)
• Higher levels of inhibin A and B are associated with oocyte presence but not with fertilization rates. (PMID:16650414)
• INHBB expression was high in human adipocytes, reduced by weight loss and adipose tissue INHBB mRNA levels correlated to metabolic risk factors. (PMID:16650820)
• A significant down-regulation of inhibin-beta (B) subunit in extravillous trophoblast cells in IUGR syncytiotrophoblast cells was demonstrated. (PMID:16670820)
• Preoperative serum inhibin B concentration could not reliably predict a response to varicocelectomy, but the increase in inhibin B levels after treatment might suggest an improvement in testicular function. (PMID:16728349)
• dimeric inhibins do not play a central role in the endocrinological imbalance observed in polycystic ovary syndrome (PMID:16758344)
• Follistatin was overexpressed while both activin subunits were downregulated in the majority of rat and human liver tumours (PMID:16935389)
• The present findings showed that treatment with vaginal estroprogestinic decreases serum inhibin A and inhibin B levels, the follicular diameter (PMID:16989826)
• 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)
• Varicocele sclerotherapy improves inhibin B levels and seminal parameters. (PMID:17376219)
• it is not clear that inhibin B does not seem to play any role in the mechanism of action of laparoscopic ovarian diathermy [letter] (PMID:17525068)
• Granulosa cell production of inhibin B is reduced by pharmacologically induced increase in the intrafollicular androgen levels. (PMID:17628551)
• decreased levels of inhibin b are associated with hot flushes, aches, joint pain, stiffness and depressed mood in the stages of menopausal transition. (PMID:17666595)
• Ovarian follicle size did influence rates of local hormone production. (PMID:17681301)
• Activin B is a potent inducer of Pdx1 as well as Shh in differentiating embryonic stem cell derived embryoid bodies (PMID:17761145)
• Activin and estrogen crosstalk regulates transcription in human breast cancer cells. (PMID:17914098)
• Used monoclonal antibody to xenopus laevis Inhbb in ELISA for detection of human Inhbb. (PMID:17991484)
• Expression of the beta-B subunit is related to decidualization and can be detected in the circulation as activin B. (PMID:18381568)
• Women with polycystic ovary syndrome have high serum concentration of total inhibin but not of inhibin A or inhibin B. (PMID:18423626)
• The degree of inhibin B increment during controlled ovarian stimulation provides a way for for predicting ovarian response to ovarian stimulation. (PMID:18555227)
• There was no significant association of (log)inhibin B profiles with age at final menstrual period. (PMID:18593767)
• Activin stimulates endogenous inhibin alpha- and betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process. (PMID:18826955)
• Functional validation of activins and bone morphogenetic protein 11 as candidate novel muscle mass regulators. (PMID:18927237)
• Antral follicle size influences serum inhibin B and FSH levels and alters their expected relationship with the number of antral follicles on day 3 (PMID:19061996)
• Serum inhibin B and estradiol concentrations obtained shortly after Gn therapy may offer an accurate and early prediction of ovarian response. (PMID:19198021)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inhbb	ENSDARG00000040777
danio_rerio	INHBB	ENSDARG00000103892
mus_musculus	Inhbb	ENSMUSG00000037035
rattus_norvegicus	Inhbb	ENSRNOG00000060237

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), 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), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Inhibin beta B chain — P09529 (reviewed: P09529)

Alternative names: Activin beta-B chain

All UniProt accessions (1): P09529

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. Activin B is a dimer of alpha and beta-B that plays a role in several essential biological processes including embryonic development, stem cell maintenance and differentiation, haematopoiesis, cell proliferation and wound healing. Signals through type I receptor ACVR1C, abundantly expressed in pancreatic beta cells, and type II receptors like ACVR2A or BMPR2. Upon ligand binding, these receptors phosphorylate intracellular signaling mediators SMAD2 and SMAD3, which form a complex with SMAD4, translocate to the nucleus, and regulate gene expression. Plays a crucial role in the induction of hepcidin by inflammation through activation of ACVR1C and subsequent phosphorylation of SMAD1/5/8. Regulates adipocyte lipid metabolism by decreasing non-esterified fatty acids and glycerol release and increases intracellular triglyceride content. Stimulates wound healing by promoting cell migration and hair follicle regeneration through the JNK and ERK signaling pathways downstream of RHOA. 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. Inhibin B is a dimer of alpha and beta-B. Activin B is a homodimer of beta-B. Activin AB is a dimer of beta-A and beta-B. Interacts with FST and FSTL3. Activin B interacts with BMPR2.

Subcellular location. Secreted.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_002184* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000381	INHBB_C	Domain
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 (25 total): strand 7, disulfide bond 5, sequence conflict 4, turn 2, signal peptide 1, propeptide 1, chain 1, helix 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7U5O	X-RAY DIFFRACTION	3.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09529-F1	75.01	0.23

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): 371, 296–304, 303–372, 332–404, 336–406

Glycosylation sites (1): 93

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1502540	Signaling by Activin
R-HSA-209822	Glycoprotein hormones
R-HSA-2473224	Antagonism of Activin by Follistatin
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

MSigDB gene sets: 373 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GU_PDEF_TARGETS_DN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, MODULE_151, PEREZ_TP63_TARGETS, LI_WILMS_TUMOR, GOBP_INSULIN_SECRETION, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP

GO Biological Process (33): ovarian follicle development (GO:0001541), defense response (GO:0006952), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), spermatogenesis (GO:0007283), cellular response to starvation (GO:0009267), response to wounding (GO:0009611), response to insecticide (GO:0017085), pituitary gland development (GO:0021983), cell differentiation (GO:0030154), negative regulation of hepatocyte growth factor production (GO:0032686), cellular response to insulin stimulus (GO:0032869), activin receptor signaling pathway (GO:0032924), response to gonadotropin (GO:0034698), cellular response to leptin stimulus (GO:0044320), fat cell differentiation (GO:0045444), negative regulation of insulin secretion (GO:0046676), positive regulation of follicle-stimulating hormone secretion (GO:0046881), negative regulation of follicle-stimulating hormone secretion (GO:0046882), oocyte development (GO:0048599), positive regulation of ovulation (GO:0060279), cellular response to calcium ion (GO:0071277), cellular response to cAMP (GO:0071320), cellular response to interleukin-1 (GO:0071347), cellular response to cholesterol (GO:0071397), seminiferous tubule development (GO:0072520), cellular response to thyroid hormone stimulus (GO:0097067), apoptotic signaling pathway (GO:0097190), cellular response to Thyroglobulin triiodothyronine (GO:1904017), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), positive regulation of apoptotic signaling pathway (GO:2001235), male gonad development (GO:0008584), female gonad development (GO:0008585), adhesion of symbiont to host cell (GO:0044650)

GO Molecular Function (6): cytokine activity (GO:0005125), hormone activity (GO:0005179), growth factor activity (GO:0008083), protein homodimerization activity (GO:0042803), host cell surface receptor binding (GO:0046789), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), perinuclear region of cytoplasm (GO:0048471), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by TGFB family members	1
Peptide hormone biosynthesis	1
Signaling by Activin	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
cellular anatomical structure	3
response to stress	2
regulation of follicle-stimulating hormone secretion	2
follicle-stimulating hormone secretion	2
female gonad development	1
anatomical structure development	1
enzyme-linked receptor protein signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
response to toxic substance	1
diencephalon development	1
endocrine system development	1
gland development	1
cellular developmental process	1
negative regulation of cytokine production	1
hepatocyte growth factor production	1
regulation of hepatocyte growth factor production	1
negative regulation of protein metabolic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
response to hormone	1
cellular response to hormone stimulus	1
response to leptin	1
cell differentiation	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
positive regulation of gonadotropin secretion	1
negative regulation of gonadotropin secretion	1
germ cell development	1
oocyte differentiation	1
ovulation	1
positive regulation of multicellular organismal process	1
regulation of ovulation	1

Protein interactions and networks

STRING

1112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INHBB	INHBA	P08476	874
INHBB	ACVR2A	P27037	869
INHBB	ACVR1C	Q8NER5	851
INHBB	INHA	P05111	736
INHBB	FST	P19883	731
INHBB	ACVR1B	P36896	712
INHBB	ACVR2B	Q13705	688
INHBB	FSHR	P23945	634
INHBB	SIX5	Q8N196	603
INHBB	BMPR2	Q13873	581
INHBB	LHCGR	P22888	519
INHBB	AMH	P03971	506
INHBB	TGFBR2	P37173	501
INHBB	HSD3B1	P14060	491
INHBB	IGFBP5	P24593	490

IntAct

4 interactions, top by confidence:

A	B	Type	Score
FNTA	INHBB	psi-mi:“MI:0915”(physical association)	0.370
INHBB	ACVR2A	psi-mi:“MI:0914”(association)	0.350
INHBB	ACVR1C	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (15): ACVR1C (Co-localization), INHBB (Reconstituted Complex), INHBB (Reconstituted Complex), INHBB (Reconstituted Complex), INHBB (Reconstituted Complex), INHBB (Proximity Label-MS), ACVR2A (Affinity Capture-Western), ACVR2B (Affinity Capture-Western), ACVR1B (Affinity Capture-Western), INHBB (Affinity Capture-RNA), ACVR2B (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), PKN1 (Affinity Capture-MS), INHBB (Co-localization), INHBB (Two-hybrid)

ESM2 similar proteins: A1A5X5, A4IH36, D4AB34, O93449, O95150, O97605, O97626, P04088, P04924, P09529, P10600, P15203, P16047, P17125, P17491, P27093, P36939, P36940, P41047, P42917, P48023, P50591, P50592, P59694, P59695, P63306, P63307, P63308, Q04999, Q07258, Q5UBV8, Q5XIG2, Q6PGN1, Q80WL1, Q861W5, Q8BGU2, Q8BMF8, Q8IUK8, Q8K3Y7, Q8R2Z0

Diamond homologs: A9CB18, G5EEL5, O08717, O13048, O46576, O60383, O61643, O77681, O88959, O95972, P03970, P07713, P07995, P08476, P09529, P09534, P12643, P12644, P17491, P18075, P18331, P21274, P21275, P25703, P27093, P27539, P30884, P30885, P35621, P42917, P43021, P43026, P43027, P43028, P43029, P43032, P48970, P49001, P55102, P55104

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

332 predictions. Top by Δscore:

Variant	Effect	Δscore
2:120346632:GACAG:G	donor_gain	1.0000
2:120346635:AGG:A	donor_loss	1.0000
2:120346638:T:G	donor_loss	1.0000
2:120349094:CGCA:C	acceptor_loss	1.0000
2:120349095:GCA:G	acceptor_loss	1.0000
2:120349096:CAGAT:C	acceptor_loss	1.0000
2:120349097:AG:A	acceptor_loss	1.0000
2:120349097:AGAT:A	acceptor_gain	1.0000
2:120349098:GATG:G	acceptor_gain	1.0000
2:120349093:CCGCA:C	acceptor_loss	0.9900
2:120349094:C:A	acceptor_gain	0.9900
2:120349097:A:AG	acceptor_gain	0.9900
2:120349097:AGATG:A	acceptor_gain	0.9900
2:120349098:G:GG	acceptor_gain	0.9900
2:120349098:GA:G	acceptor_gain	0.9900
2:120349098:GAT:G	acceptor_gain	0.9900
2:120349098:GATGG:G	acceptor_gain	0.9900
2:120346635:AGGTG:A	donor_gain	0.9800
2:120346637:G:GG	donor_gain	0.9800
2:120347630:G:T	donor_gain	0.9600
2:120347645:T:G	donor_gain	0.9600
2:120347630:G:GT	donor_gain	0.9400
2:120347641:GC:G	donor_gain	0.9300
2:120349100:T:TA	acceptor_gain	0.9200
2:120347619:T:TA	donor_gain	0.9100
2:120347371:GG:G	donor_gain	0.8400
2:120347372:GG:G	donor_gain	0.8400
2:120347360:T:TA	donor_gain	0.7700
2:120347361:A:AA	donor_gain	0.7700
2:120348977:C:A	acceptor_gain	0.7600

AlphaMissense

2635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:120346505:C:A	A106D	1.000
2:120346621:A:C	S145R	1.000
2:120346623:C:A	S145R	1.000
2:120346623:C:G	S145R	1.000
2:120346624:T:C	F146L	1.000
2:120346625:T:G	F146C	1.000
2:120346626:C:A	F146L	1.000
2:120346626:C:G	F146L	1.000
2:120349326:T:A	W226R	1.000
2:120349326:T:C	W226R	1.000
2:120349328:G:C	W226C	1.000
2:120349328:G:T	W226C	1.000
2:120349471:C:A	P274H	1.000
2:120349473:T:C	F275L	1.000
2:120349475:T:A	F275L	1.000
2:120349475:T:G	F275L	1.000
2:120349557:T:A	C303S	1.000
2:120349557:T:C	C303R	1.000
2:120349558:G:A	C303Y	1.000
2:120349558:G:C	C303S	1.000
2:120349559:T:G	C303W	1.000
2:120349584:T:C	F312L	1.000
2:120349585:T:G	F312C	1.000
2:120349586:C:A	F312L	1.000
2:120349586:C:G	F312L	1.000
2:120349599:T:A	W317R	1.000
2:120349599:T:C	W317R	1.000
2:120349601:G:C	W317C	1.000
2:120349601:G:T	W317C	1.000
2:120349608:T:A	W320R	1.000

dbSNP variants (sampled 300 via entrez): RS1000200391 (2:120346279 A>C), RS1000606272 (2:120351918 G>A), RS1000829657 (2:120347611 G>A,C), RS1001095566 (2:120349462 C>G,T), RS1001218969 (2:120346936 A>G), RS1002159794 (2:120348887 C>G), RS1002213607 (2:120349127 A>G), RS1002253835 (2:120344304 T>A,C), RS1002306229 (2:120344505 G>A), RS1002491705 (2:120347491 A>G), RS1002524282 (2:120347767 G>A), RS1002875809 (2:120346181 G>A,C,T), RS1002928098 (2:120346453 C>A,G,T), RS1003212911 (2:120345187 C>T), RS1003265182 (2:120345379 G>A,C)

Disease associations

OMIM: gene MIM:147390 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001057_6	Obesity	2.000000e-07
GCST001585_19	Breast size	3.000000e-11
GCST001585_23	Breast size	5.000000e-10
GCST001791_23	Urate levels	2.000000e-10
GCST001814_12	Age-related macular degeneration	7.000000e-06
GCST001814_24	Age-related macular degeneration	5.000000e-07
GCST003842_5	Breast cancer (estrogen-receptor negative)	9.000000e-07
GCST003845_5	Breast cancer	7.000000e-10
GCST003985_2	Breast size	6.000000e-18
GCST010637_4	Urate levels	6.000000e-11
GCST90011900_131	Serum alkaline phosphatase levels	4.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression, decreases methylation, increases expression	5
Acetaminophen	increases expression, decreases expression	3
Nickel	decreases expression, decreases reaction, affects expression	3
Cyclosporine	increases expression	3
bisphenol A	decreases secretion, affects cotreatment, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance, affects expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Vitamin K 3	affects expression, increases expression	2
bisphenol F	increases expression, affects cotreatment	1
pirinixic acid	affects binding, increases activity, increases expression	1
potassium perchlorate	decreases expression	1
terbufos	increases methylation	1
trichostatin A	affects expression, decreases reaction	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
didecyldimethylammonium	decreases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
1-nitropyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
obeticholic acid	increases expression	1
abrine	decreases expression	1

Clinical trials (associated diseases)

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