GDF1

growth differentiation factor 1, the group of Transforming growth factor beta superfamily

Basic information

Region (hg38): 19:18868544-18896158

Links

ENSG00000130283 ∙ NCBI:2657 ∙ OMIM:602880 ∙ HGNC:4214 ∙ Uniprot:P27539 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tetralogy of fallot (Limited), mode of inheritance: AD
• congenital heart defects, multiple types, 6 (Limited), mode of inheritance: AD
• conotruncal heart malformations (Limited), mode of inheritance: AD
• congenital heart defects, multiple types, 6 (Limited), mode of inheritance: AD
• right atrial isomerism (Limited), mode of inheritance: AR
• right atrial isomerism (Supportive), mode of inheritance: AR
• congenital heart defects, multiple types, 6 (No Known Disease Relationship), mode of inheritance: AD
• congenital heart defects, multiple types, 6 (Definitive), mode of inheritance: AR
• conotruncal heart malformations (Limited), mode of inheritance: Unknown
• right atrial isomerism (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, multiple types, 6; Right atrial isomerism	AD/AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Gastrointestinal; Pulmonary	17924340; 20413652; 28991257

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GDF1 gene.

• Progressive myoclonic epilepsy type 8 (264 variants)
• not provided (119 variants)
• Inborn genetic diseases (38 variants)
• not specified (14 variants)
• Congenital heart defects, multiple types, 6 (9 variants)
• GDF1-related condition (7 variants)
• Visceral heterotaxy (4 variants)
• Right atrial isomerism (3 variants)
• Right atrial isomerism;Congenital heart defects, multiple types, 6 (2 variants)
• Tetralogy of Fallot (1 variants)
• - (1 variants)
• Heart, malformation of (1 variants)
• GDF1-RELATED DISORDERS (1 variants)
• Double outlet right ventricle (1 variants)
• Heterotaxy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDF1 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			4	30		34
missense		5	62	2	1	70
nonsense	2	5				7
start loss						0
frameshift	5	6	3			14
inframe indel			4		2	6
splice donor/acceptor (+/-2bp)			1			1
splice region			11	15	2	28
non coding	1		124	109	7	241
Total	8	16	198	141	10

Highest pathogenic variant AF is 0.000215

Variants in GDF1

This is a list of pathogenic ClinVar variants found in the GDF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-18868612-C-T			Likely benign (Sep 06, 2019)
19-18868614-C-T		not specified	Uncertain significance (Oct 05, 2023)
19-18868620-C-A		not specified	Uncertain significance (Dec 08, 2021)
19-18868621-C-T			Likely benign (Aug 27, 2022)
19-18868623-CCAT-C		Right atrial isomerism	Pathogenic (Apr 18, 2018)
19-18868624-C-T			Likely pathogenic (Apr 02, 2021)
19-18868625-A-G		Congenital heart defects, multiple types, 6 • Heart, malformation of	Pathogenic/Likely pathogenic (Sep 08, 2023)
19-18868641-G-A			Uncertain significance (Oct 13, 2022)
19-18868664-T-TCAAAGAAGAGCA			Uncertain significance (May 11, 2020)
19-18868665-CAAAG-C		Congenital heart defects, multiple types, 6	Pathogenic/Likely pathogenic (Jan 25, 2023)
19-18868666-AAAG-A		Visceral heterotaxy • Progressive myoclonic epilepsy type 8	Uncertain significance (Aug 31, 2021)
19-18868673-A-G			Uncertain significance (Jul 28, 2023)
19-18868675-C-A		GDF1-related disorder	Likely benign (May 29, 2022)
19-18868678-G-A			Likely benign (Apr 02, 2018)
19-18868681-G-A			Likely benign (Feb 23, 2023)
19-18868686-G-A			Uncertain significance (Sep 01, 2021)
19-18868687-C-T		Progressive myoclonic epilepsy type 8	Likely benign (Jul 10, 2018)
19-18868688-G-C			Uncertain significance (Aug 08, 2019)
19-18868697-G-C			Uncertain significance (Dec 03, 2020)
19-18868700-G-A		not specified	Uncertain significance (Aug 08, 2022)
19-18868700-G-T			Uncertain significance (Dec 05, 2020)
19-18868708-G-C		-	no classification for the single variant (-)
19-18868715-A-C		not specified	Uncertain significance (Jan 27, 2022)
19-18868719-C-T		Congenital heart defects, multiple types, 6	Uncertain significance (Sep 10, 2018)
19-18868729-C-T			Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GDF1	protein_coding	protein_coding	ENST00000247005	2	27545

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.412	0.555	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.69	102	163	0.626	0.0000121	2207
Missense in Polyphen		39	69.186	0.5637		836
Synonymous	1.95	59	81.4	0.725	0.00000681	889
Loss of Function	1.70	1	5.17	0.194	2.61e-7	72

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May mediate cell differentiation events during embryonic development.
• Disease: DISEASE: Congenital heart defects, multiple types, 6 (CHTD6) [MIM:613854]: An autosomal dominant disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, transposition of the great arteries, double-outlet right ventricle, total anomalous pulmonary venous return, pulmonary stenosis or atresia, atrioventricular canal, ventricular septal defect, and hypoplastic left or right ventricle. {ECO:0000269|PubMed:17924340, ECO:0000269|PubMed:28991257}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. {ECO:0000269|PubMed:17924340}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Right atrial isomerism (RAI) [MIM:208530]: A severe complex congenital heart defect resulting from embryonic disruption of proper left-right axis determination. RAI is usually characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries. Affected individuals present at birth with severe cardiac failure. Other associated abnormalities include bilateral trilobed lungs, midline liver, and asplenia, as well as situs inversus affecting other organs. {ECO:0000269|PubMed:20413652, ECO:0000269|PubMed:28991257}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: TGF-Core;Metabolism of lipids;Metabolism;ceramide <i>de novo</i> biosynthesis;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.121

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.285
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gdf1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; digestive/alimentary 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); immune system phenotype

Gene ontology

• Biological process: regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;BMP signaling pathway;regulation of apoptotic process;regulation of MAPK cascade;cell development;SMAD protein signal transduction
• Cellular component: extracellular space
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;growth factor activity