GDF11

growth differentiation factor 11, the group of Transforming growth factor beta superfamily

Basic information

Region (hg38): 12:55743121-55757264

Links

ENSG00000135414 ∙ NCBI:10220 ∙ OMIM:603936 ∙ HGNC:4216 ∙ Uniprot:O95390 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vertebral hypersegmentation and orofacial anomalies (Strong), mode of inheritance: AD
• vertebral hypersegmentation and orofacial anomalies (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vertebral hypersegmentation and orofacial anomalies	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	31215115

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GDF11 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDF11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			13	1		14
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel				2		2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	3	0

Variants in GDF11

This is a list of pathogenic ClinVar variants found in the GDF11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-55743378-G-C		not specified	Uncertain significance (Sep 22, 2022)
12-55743400-CGCG-C		GDF11-related disorder	Likely benign (Feb 08, 2022)
12-55743400-CGCGGCGGCG-C		GDF11-related disorder	Likely benign (May 17, 2023)
12-55743470-G-T			Uncertain significance (Dec 14, 2023)
12-55743611-G-A		not specified	Uncertain significance (Jul 12, 2023)
12-55743618-A-AG		Vertebral hypersegmentation and orofacial anomalies	Uncertain significance (Sep 08, 2021)
12-55743695-G-A		not specified	Uncertain significance (Jan 24, 2023)
12-55743735-A-C		not specified	Uncertain significance (Jun 16, 2024)
12-55743758-G-C		not specified	Uncertain significance (Sep 17, 2021)
12-55748765-G-A		not specified	Uncertain significance (Jun 01, 2023)
12-55748768-G-C		not specified	Uncertain significance (May 08, 2024)
12-55748769-G-T		GDF11-related disorder	Likely benign (Feb 16, 2023)
12-55748777-G-A		not specified	Uncertain significance (May 03, 2023)
12-55748832-G-A		not specified	Uncertain significance (Dec 12, 2023)
12-55748862-A-C		not specified	Uncertain significance (Jul 25, 2023)
12-55748864-C-G		not specified	Uncertain significance (Feb 10, 2022)
12-55748951-G-A		not specified	Uncertain significance (Feb 03, 2022)
12-55748975-G-A		not specified	Uncertain significance (Jan 26, 2022)
12-55749551-G-A		Orofacial cleft • Vertebral hypersegmentation and orofacial anomalies	Pathogenic/Likely pathogenic (Dec 08, 2020)
12-55749574-G-A		Vertebral hypersegmentation and orofacial anomalies	Uncertain significance (Dec 01, 2021)
12-55749579-C-G		not specified	Uncertain significance (Mar 25, 2024)
12-55749625-G-C		not specified	Uncertain significance (Aug 01, 2023)
12-55749662-G-A		Vertebral hypersegmentation and orofacial anomalies	Uncertain significance (Aug 22, 2022)
12-55749666-C-G		GDF11-associated multiple congenital anomalies and ID	Uncertain significance (Oct 06, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GDF11	protein_coding	protein_coding	ENST00000257868	3	13848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.976	0.0235	125736	0	2	125738	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.98	104	232	0.449	0.0000140	2613
Missense in Polyphen		18	69.311	0.2597		689
Synonymous	1.67	71	91.3	0.778	0.00000524	853
Loss of Function	3.47	1	15.9	0.0628	9.22e-7	151

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Secreted signal that acts globally to specify positional identity along the anterior/posterior axis during development. May play critical roles in patterning both mesodermal and neural tissues and in establishing the skeletal pattern (By similarity). Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3 (PubMed:28257634). {ECO:0000250|UniProtKB:Q9Z1W4, ECO:0000269|PubMed:28257634}.
• Pathway: TGF-Core;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;BMP signaling Dro (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• loftool: 0.230
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.599
• hipred: Y
• hipred_score: 0.729
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.611

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gdf11
• Phenotype: immune system phenotype; renal/urinary system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; embryo phenotype; respiratory system phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype

Zebrafish Information Network

• Gene name: gdf11
• Affected structure: exocrine pancreas
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: skeletal system development;metanephros development;ureteric bud development;nervous system development;mesoderm development;negative regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;spinal cord anterior/posterior patterning;pancreas development;regulation of apoptotic process;regulation of MAPK cascade;negative regulation of neuron differentiation;cell development;cell maturation;camera-type eye morphogenesis;roof of mouth development;SMAD protein signal transduction
• Cellular component: cellular_component;extracellular space;nucleoplasm;protein-containing complex;intracellular membrane-bounded organelle
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity