TGFBR3L

Summary

TGFBR3L (transforming growth factor beta receptor 3 like, HGNC:44152) is a protein-coding gene on chromosome 19p13.2, encoding Transforming growth factor-beta receptor type 3-like protein (H3BV60). Expressed in gonadotrope cells, acts as an inhibin B coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility.

Predicted to enable glycosaminoglycan binding activity; transforming growth factor beta receptor activity; and type II transforming growth factor beta receptor binding activity. Predicted to contribute to transforming growth factor beta binding activity. Predicted to be involved in several processes, including epithelial to mesenchymal transition; regulation of transforming growth factor beta receptor signaling pathway; and transforming growth factor beta receptor signaling pathway. Predicted to be located in plasma membrane.

Source: NCBI Gene 100507588 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_001419781

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44152
Approved symbol	TGFBR3L
Name	transforming growth factor beta receptor 3 like
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	GEMP
Ensembl gene	ENSG00000260001
Ensembl biotype	protein_coding
Entrez	100507588

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000564348, ENST00000565886, ENST00000566166, ENST00000713907, ENST00000713908, ENST00000869760

RefSeq mRNA: 2 — MANE Select: NM_001419781 NM_001195259, NM_001419781

Canonical transcript exons

ENST00000713907 — 7 exons

Exon	Start	End
ENSE00002576029	7914830	7914923
ENSE00002603992	7918917	7919097
ENSE00004021760	7916407	7916543
ENSE00004021774	7918057	7918129
ENSE00004021775	7917701	7917859
ENSE00004021776	7916622	7916942
ENSE00004021777	7917473	7917599

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2153 / max 3706.2269, expressed in 1202 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173621	2.8089	10
173625	1.1324	479
173624	0.9308	583
173623	0.8423	419
173628	0.4040	132
173629	0.3978	217
173620	0.3262	6
173626	0.2545	87
173619	0.0571	3
173618	0.0367	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	97.95	gold quality
adenohypophysis	UBERON:0002196	97.79	gold quality
superior frontal gyrus	UBERON:0002661	93.80	gold quality
primary visual cortex	UBERON:0002436	93.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.89	gold quality
cerebellar vermis	UBERON:0004720	91.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.80	gold quality
anterior cingulate cortex	UBERON:0009835	90.07	gold quality
right frontal lobe	UBERON:0002810	89.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.02	gold quality
frontal cortex	UBERON:0001870	88.82	gold quality
cerebellum	UBERON:0002037	88.19	gold quality
cerebellar cortex	UBERON:0002129	88.14	gold quality
cerebellar hemisphere	UBERON:0002245	88.05	gold quality
prefrontal cortex	UBERON:0000451	88.03	gold quality
temporal lobe	UBERON:0001871	87.94	gold quality
amygdala	UBERON:0001876	87.81	gold quality
cerebral cortex	UBERON:0000956	87.80	gold quality
apex of heart	UBERON:0002098	87.33	gold quality
brain	UBERON:0000955	85.55	gold quality
quadriceps femoris	UBERON:0001377	84.61	gold quality
Ammon’s horn	UBERON:0001954	83.19	gold quality
putamen	UBERON:0001874	83.14	gold quality
hypothalamus	UBERON:0001898	81.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.17	gold quality
caudate nucleus	UBERON:0001873	80.66	gold quality
nucleus accumbens	UBERON:0001882	79.90	gold quality
stromal cell of endometrium	CL:0002255	79.36	gold quality
right atrium auricular region	UBERON:0006631	78.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting TGFBR3L, 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-6825-5P	99.96	69.81	3431
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-7706	95.96	63.68	172
HSA-MIR-4281	92.91	63.60	271

Literature-anchored findings (GeneRIF, showing 2)

• Data show that the rs11669203 G>C polymorphism, located in transforming growth factor-beta receptor type 3-like protein (TGFBR3L) promoter, is significantly associated with the risk of neuroblastoma (NB). (PMID:26468016)
• TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours. (PMID:36952069)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tgfbr3l	ENSMUSG00000089736
rattus_norvegicus	Tgfbr3l	ENSRNOG00000050573

Paralogs (2): TGFBR3 (ENSG00000069702), ENG (ENSG00000106991)

Protein

Protein identifiers

Transforming growth factor-beta receptor type 3-like protein — H3BV60 (reviewed: H3BV60)

Alternative names: TGF-beta receptor type-3-like protein, Transforming growth factor-beta receptor type III-like protein

All UniProt accessions (2): A0AAQ5BH11, H3BV60

UniProt curated annotations — full annotation on UniProt →

Function. Expressed in gonadotrope cells, acts as an inhibin B coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in pituitary gland gonadotrope cells.

Post-translational modifications. Glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
H3BV60-1	1	yes
H3BV60-2	2

RefSeq proteins (2): NP_001182188, NP_001406710* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR042235	ZP-C_dom	Homologous_superfamily
IPR055355	ZP-C	Domain

Pfam: PF00100

UniProt features (14 total): compositionally biased region 3, topological domain 2, region of interest 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-H3BV60-F1	73.26	0.32

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 (1): 85–147

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOMF_TRANSMEMBRANE_RECEPTOR_PROTEIN_KINASE_ACTIVITY, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_MESENCHYME_DEVELOPMENT, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_TRANSFORMING_GROWTH_FACTOR_BETA_RECEPTOR_SIGNALING_PATHWAY, chr19p13, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_CYTOKINE_BINDING

GO Biological Process (4): epithelial to mesenchymal transition (GO:0001837), transforming growth factor beta receptor signaling pathway (GO:0007179), cell migration (GO:0016477), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015)

GO Molecular Function (4): transforming growth factor beta receptor activity (GO:0005024), type II transforming growth factor beta receptor binding (GO:0005114), glycosaminoglycan binding (GO:0005539), transforming growth factor beta binding (GO:0050431)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mesenchymal cell differentiation	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to transforming growth factor beta stimulus	1
transmembrane receptor protein serine/threonine kinase activity	1
transforming growth factor beta receptor binding	1
carbohydrate derivative binding	1
growth factor binding	1
cytokine binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGFBR3L	PAPPA2	Q9BXP8	355
TGFBR3L	CCDC177	Q9NQR7	331
TGFBR3L	GPR150	Q8NGU9	319
TGFBR3L	ACAA2	P42765	316
TGFBR3L	PINK1	Q9BXM7	311
TGFBR3L	POU1F1	P28069	306
TGFBR3L	TBX19	O60806	300
TGFBR3L	HEPACAM2	A8MVW5	295
TGFBR3L	ZSWIM6	Q9HCJ5	294
TGFBR3L	ZCCHC2	Q9C0B9	291
TGFBR3L	HSD17B12	Q53GQ0	291
TGFBR3L	SIRT1	Q96EB6	289
TGFBR3L	DUSP15	Q9H1R2	286
TGFBR3L	SIRT2	Q8IXJ6	279
TGFBR3L	TGFBRAP1	Q8WUH2	272
TGFBR3L	FBXL17	Q9UF56	272

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A1L515, A2A9Q0, D3YZZ2, D4A2Q0, E1BDF2, E7ERA6, F2Z333, H3BV60, O43508, O46547, O54907, P0C6B2, P0DH78, P41155, P51172, P70225, Q01113, Q13477, Q14626, Q29RT8, Q5RF19, Q5SZI1, Q5T7M4, Q5U4P2, Q63148, Q64385, Q6AZ51, Q6BAA4, Q6UWL6, Q6UXT9, Q6ZMC9, Q86UR1, Q86YD3, Q8BH06, Q8N1F8, Q8NFR9, Q96G42, Q99640, Q99M75, Q99MF4

Diamond homologs: D3YZZ2, H3BV60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

968 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7917471:A:AG	acceptor_gain	1.0000
19:7917472:G:GG	acceptor_gain	1.0000
19:7917472:GT:G	acceptor_gain	1.0000
19:7917472:GTGT:G	acceptor_gain	1.0000
19:7917600:G:GG	donor_gain	1.0000
19:7916541:CAGGT:C	donor_loss	0.9900
19:7916542:AG:A	donor_loss	0.9900
19:7916543:GG:G	donor_loss	0.9900
19:7916544:GTG:G	donor_loss	0.9900
19:7916862:C:G	donor_gain	0.9900
19:7916886:G:GT	donor_gain	0.9900
19:7916886:G:T	donor_gain	0.9900
19:7917470:CAGT:C	acceptor_loss	0.9900
19:7917471:AGT:A	acceptor_gain	0.9900
19:7917472:GTG:G	acceptor_gain	0.9900
19:7917472:GTGTC:G	acceptor_gain	0.9900
19:7917017:A:T	donor_gain	0.9800
19:7917597:CCAGT:C	donor_loss	0.9800
19:7917599:AG:A	donor_loss	0.9800
19:7917600:G:GC	donor_loss	0.9800
19:7917601:T:TG	donor_loss	0.9800
19:7917602:G:GG	donor_loss	0.9800
19:7916541:C:T	donor_gain	0.9700
19:7917023:GA:G	donor_gain	0.9700
19:7917457:C:G	acceptor_gain	0.9700
19:7917473:T:TA	acceptor_gain	0.9700
19:7917603:AG:A	donor_loss	0.9700
19:7917604:G:C	donor_loss	0.9700
19:7917010:G:GT	donor_gain	0.9600
19:7917456:A:AG	acceptor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000082187 (19:7913169 C>G,T), RS1000158066 (19:7913408 T>C), RS1000267087 (19:7918731 G>A), RS1000890710 (19:7916777 G>A,T), RS1001084460 (19:7914141 G>T), RS1001924076 (19:7916661 C>T), RS1002111324 (19:7915010 T>C), RS1002142595 (19:7915199 T>G), RS1002674953 (19:7914094 T>C), RS1002853325 (19:7919335 G>T), RS1003150613 (19:7916742 G>A,C,T), RS1003598674 (19:7915265 C>A,T), RS1003693477 (19:7915075 A>G), RS1003966148 (19:7913767 CAAG>C), RS1004003920 (19:7913059 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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