GDF7

Summary

GDF7 (growth differentiation factor 7, HGNC:4222) is a protein-coding gene on chromosome 2p24.1, encoding Growth/differentiation factor 7 (Q7Z4P5). May play an active role in the motor area of the primate neocortex.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein may play a role in the differentiation of tendon cells and spinal cord interneurons. A mutation in this gene may be associated with increased risk for Barrett’s esophagus and esophageal adenocarcinoma.

Source: NCBI Gene 151449 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_182828

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4222
Approved symbol	GDF7
Name	growth differentiation factor 7
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	BMP12
Ensembl gene	ENSG00000143869
Ensembl biotype	protein_coding
OMIM	604651
Entrez	151449

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000272224

RefSeq mRNA: 1 — MANE Select: NM_182828 NM_182828

CCDS: CCDS1701

Canonical transcript exons

ENST00000272224 — 2 exons

Exon	Start	End
ENSE00001159259	20670464	20679243
ENSE00001276783	20667144	20667630

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 90.79.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6455 / max 47.4456, expressed in 194 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19133	0.3692	135
19134	0.2763	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	90.79	gold quality
endometrium	UBERON:0001295	88.07	gold quality
blood vessel layer	UBERON:0004797	88.04	gold quality
cervix squamous epithelium	UBERON:0006922	83.06	gold quality
descending thoracic aorta	UBERON:0002345	82.01	gold quality
thoracic aorta	UBERON:0001515	81.27	gold quality
ascending aorta	UBERON:0001496	81.07	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.19	silver quality
uterus	UBERON:0000995	79.58	gold quality
aorta	UBERON:0000947	77.03	gold quality
ectocervix	UBERON:0012249	76.29	gold quality
right coronary artery	UBERON:0001625	75.92	gold quality
uterine cervix	UBERON:0000002	75.43	gold quality
endocervix	UBERON:0000458	75.35	gold quality
type B pancreatic cell	CL:0000169	75.12	gold quality
mucosa of urinary bladder	UBERON:0001259	75.08	gold quality
olfactory bulb	UBERON:0002264	75.04	gold quality
nephron tubule	UBERON:0001231	74.48	gold quality
popliteal artery	UBERON:0002250	73.92	gold quality
tibial artery	UBERON:0007610	73.91	gold quality
vagina	UBERON:0000996	73.78	gold quality
epithelium of nasopharynx	UBERON:0001951	73.29	silver quality
kidney epithelium	UBERON:0004819	73.26	silver quality
right lobe of liver	UBERON:0001114	73.12	gold quality
myometrium	UBERON:0001296	72.50	gold quality
liver	UBERON:0002107	72.27	gold quality
esophagus squamous epithelium	UBERON:0006920	72.08	silver quality
epithelial cell of pancreas	CL:0000083	72.01	gold quality
endothelial cell	CL:0000115	72.00	gold quality
metanephric glomerulus	UBERON:0004736	71.83	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	103.87
E-ANND-3	yes	4.21
E-HCAD-8	no	105.61
E-MTAB-6058	no	72.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): OTX2

Literature-anchored findings (GeneRIF, showing 11)

• In mouse, the expression of Gdf7 in roof plate cells is required for the fidelity of commissural axon growth. (PMID:12741987)
• stimulates expression of both chondrogenic and osteoblstic markers in pluripotent mesenchymal C3H10T1/2 cells. (PMID:20102312)
• induces ligamentogenic differentiation in mesenchymal progenitors (PMID:20334610)
• studies show that even though tenogenic (BMP 12 and BMP 13) and osteogenic (BMP2) BMPs bind the same receptors with high affinity they signal much differently and result in differential activation of osteogenic and tenogenic markers (PMID:21702718)
• BMP12 induces tenogenic differentiation of adipose-derived stromal cells via the Smad1/5/8 pathway. (PMID:24155967)
• closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development (PMID:25447851)
• The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk. (PMID:26783083)
• BMP-12 activates tenogenic pathway in human adipose stem cells. (PMID:28214472)
• TET-dependent GDF7 hypomethylation impairs aqueous humor outflow and serves as a potential therapeutic target in glaucoma. (PMID:33388417)
• Secretome screening reveals immunomodulating functions of IFNalpha-7, PAP and GDF-7 on regulatory T-cells. (PMID:34408239)
• Growth differentiation factor 7 autocrine signaling promotes hepatic progenitor cell expansion in liver fibrosis. (PMID:37798809)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gdf6b	ENSDARG00000005510
danio_rerio	gdf7	ENSDARG00000042784
danio_rerio	gdf6a	ENSDARG00000053479
mus_musculus	Gdf7	ENSMUSG00000037660
rattus_norvegicus	Gdf7	ENSRNOG00000088409

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), 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

Growth/differentiation factor 7 — Q7Z4P5 (reviewed: Q7Z4P5)

All UniProt accessions (1): Q7Z4P5

UniProt curated annotations — full annotation on UniProt →

Function. May play an active role in the motor area of the primate neocortex.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Secreted.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_878248* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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 (11 total): disulfide bond 4, 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)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4P5-F1	72.03	0.33

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 (4): 349–415, 378–447, 382–449, 414

Glycosylation sites (1): 83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_FOREBRAIN_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD

GO Biological Process (20): axon guidance (GO:0007411), positive regulation of gene expression (GO:0010628), roof plate formation (GO:0021509), spinal cord association neuron differentiation (GO:0021527), gland morphogenesis (GO:0022612), BMP signaling pathway (GO:0030509), epithelial cell differentiation (GO:0030855), midbrain development (GO:0030901), activin receptor signaling pathway (GO:0032924), cell fate commitment (GO:0045165), positive regulation of neuron differentiation (GO:0045666), positive regulation of DNA-templated transcription (GO:0045893), reproductive structure development (GO:0048608), branching morphogenesis of an epithelial tube (GO:0048754), forebrain morphogenesis (GO:0048853), positive regulation of SMAD protein signal transduction (GO:0060391), morphogenesis of an epithelial fold (GO:0060571), positive regulation of tendon cell differentiation (GO:2001051), neural tube development (GO:0021915), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092)

GO Molecular Function (4): cytokine activity (GO:0005125), growth factor activity (GO:0008083), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transforming growth factor beta receptor superfamily signaling pathway	2
cell differentiation	2
epithelium development	2
anatomical structure development	2
positive regulation of cell differentiation	2
receptor ligand activity	2
axonogenesis	1
neuron projection guidance	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
neural tube formation	1
anatomical structure formation involved in morphogenesis	1
cell differentiation in spinal cord	1
dorsal spinal cord development	1
central nervous system neuron differentiation	1
animal organ morphogenesis	1
gland development	1
cellular response to BMP stimulus	1
brain development	1
cellular developmental process	1
neuron differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
developmental process involved in reproduction	1
reproductive system development	1
tube morphogenesis	1
epithelial tube morphogenesis	1
morphogenesis of a branching epithelium	1
anatomical structure morphogenesis	1
forebrain development	1
brain morphogenesis	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
morphogenesis of an epithelium	1
tendon cell differentiation	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDF7	PAEP	P09466	875
GDF7	BMPR1B	P78366	758
GDF7	TNMD	Q9H2S6	720
GDF7	ACVR2A	P27037	669
GDF7	BMPR1A	P36894	642
GDF7	BMPR2	Q13873	640
GDF7	BMP7	P18075	639
GDF7	WNT1	P04628	580
GDF7	FST	P19883	566
GDF7	CHRD	Q9H2X0	527
GDF7	NOG	Q13253	515
GDF7	ACVR2B	Q13705	499
GDF7	BGLAP	P02818	496
GDF7	SCX	Q7RTU7	496
GDF7	MKX	Q8IYA7	494

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2A699, A2XVC2, A8MVW0, B0F2B4, D3ZE55, O09017, O14492, O62763, O95206, P10588, P21836, P22303, P23795, P36196, P37136, P43029, P43136, P50427, Q14003, Q29RK8, Q2QXZ2, Q2RAQ5, Q3U0S6, Q495W5, Q4ACU6, Q5T442, Q5U651, Q5ZMM1, Q62888, Q62889, Q63959, Q69ZK9, Q6UXK2, Q76KP1, Q7FA29, Q7Z4P5, Q80WV3, Q80XF7, Q869C3, Q8BQU6

Diamond homologs: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, A8E7N9, G5EEL5, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O46576, O61643, O95390, O95393, P09534, P12644, P12645, P17491, P18075, P20722, P20863, P22003, P22004, P22444, P23359, P27091, P27539, P35621, P43026, P43027, P43028, P43029, P48970

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

494 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20670451:C:A	acceptor_gain	0.9900
2:20667626:CCAAG:C	donor_loss	0.9700
2:20667627:CAAG:C	donor_loss	0.9700
2:20667628:AAGGT:A	donor_loss	0.9700
2:20667630:GGTAC:G	donor_loss	0.9700
2:20667631:G:C	donor_loss	0.9700
2:20667632:T:G	donor_loss	0.9700
2:20670448:T:TA	acceptor_gain	0.9700
2:20670452:G:A	acceptor_gain	0.9700
2:20671401:G:GA	donor_gain	0.9700
2:20668028:G:GA	donor_gain	0.9600
2:20668038:A:AG	donor_gain	0.9600
2:20670462:A:AG	acceptor_gain	0.9600
2:20670463:G:GG	acceptor_gain	0.9600
2:20668027:T:TA	donor_gain	0.9500
2:20669894:G:T	donor_gain	0.9500
2:20670462:AGAC:A	acceptor_gain	0.9500
2:20670463:GAC:G	acceptor_gain	0.9500
2:20670463:GACG:G	acceptor_gain	0.9500
2:20668000:G:GT	donor_gain	0.9300
2:20671400:T:TA	donor_gain	0.9300
2:20670463:GACGA:G	acceptor_gain	0.9200
2:20667978:G:GT	donor_gain	0.9000
2:20670460:GCAGA:G	acceptor_loss	0.9000
2:20670461:CAGAC:C	acceptor_loss	0.9000
2:20670462:A:G	acceptor_loss	0.9000
2:20670459:C:CA	acceptor_gain	0.8900
2:20667983:C:T	donor_gain	0.8800
2:20669903:GC:G	donor_gain	0.8800
2:20671393:G:GT	donor_gain	0.8700

AlphaMissense

2842 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20671144:T:C	F358L	1.000
2:20671145:T:C	F358S	1.000
2:20671145:T:G	F358C	1.000
2:20671146:C:A	F358L	1.000
2:20671146:C:G	F358L	1.000
2:20671159:T:A	W363R	1.000
2:20671159:T:C	W363R	1.000
2:20671161:G:C	W363C	1.000
2:20671161:G:T	W363C	1.000
2:20671170:G:C	W366C	1.000
2:20671170:G:T	W366C	1.000
2:20671217:G:A	C382Y	1.000
2:20671223:T:G	F384C	1.000
2:20671316:G:A	C415Y	1.000
2:20671144:T:A	F358I	0.999
2:20671168:T:A	W366R	0.999
2:20671168:T:C	W366R	0.999
2:20671172:T:A	I367N	0.999
2:20671172:T:C	I367T	0.999
2:20671172:T:G	I367S	0.999
2:20671175:T:A	I368N	0.999
2:20671181:C:A	P370Q	0.999
2:20671204:T:A	C378S	0.999
2:20671204:T:C	C378R	0.999
2:20671205:G:A	C378Y	0.999
2:20671205:G:C	C378S	0.999
2:20671205:G:T	C378F	0.999
2:20671206:C:G	C378W	0.999
2:20671210:G:C	G380R	0.999
2:20671210:G:T	G380C	0.999

dbSNP variants (sampled 300 via entrez): RS1000113006 (2:20668128 C>T), RS1000163727 (2:20667839 C>T), RS1000283478 (2:20668643 C>G,T), RS1000335571 (2:20668920 C>T), RS1000502077 (2:20666182 G>A,T), RS1000848049 (2:20677872 G>A), RS1000923089 (2:20678222 T>C), RS1001032037 (2:20673014 A>T), RS1001053835 (2:20677906 T>C), RS1001404446 (2:20669963 C>T), RS1001955238 (2:20669901 A>C), RS1002164605 (2:20678871 A>G), RS1002336043 (2:20666686 C>T), RS1002497433 (2:20666822 G>A,C,T), RS1002988854 (2:20675904 C>T)

Disease associations

OMIM: gene MIM:604651 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000635_13	Response to statin therapy	8.000000e-06
GCST003739_5	Esophageal adenocarcinoma	4.000000e-08
GCST003740_1	Barrett’s esophagus or Esophageal adenocarcinoma	9.000000e-11
GCST003877_12	Abdominal aortic aneurysm	1.000000e-06
GCST007096_4	Pulse pressure	2.000000e-15
GCST007097_65	Pulse pressure	4.000000e-06
GCST007097_66	Pulse pressure	3.000000e-06
GCST010174_2	Pelvic organ prolapse	3.000000e-17
GCST90014033_6	Haemorrhoidal disease	7.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
terbufos	increases methylation	1
tetrabromobisphenol A	decreases expression	1
tetrachlorodian	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Fonofos	increases methylation	1
Oxygen	increases expression	1
Parathion	increases methylation	1
Rotenone	increases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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