GREM2

gremlin 2, DAN family BMP antagonist, the group of DAN family

Basic information

Region (hg38): 1:240489572-240612155

Links

ENSG00000180875 ∙ NCBI:64388 ∙ OMIM:608832 ∙ HGNC:17655 ∙ Uniprot:Q9H772 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tooth agenesis, selective, 9	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	Dental; Dermatologic	26416033

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GREM2 gene.

• Inborn genetic diseases (7 variants)
• Tooth agenesis, selective, 9 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GREM2 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	1		8			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	8	0	0

Highest pathogenic variant AF is 0.000105

Variants in GREM2

This is a list of pathogenic ClinVar variants found in the GREM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-240493063-G-C		not specified	Uncertain significance (Oct 12, 2021)
1-240493068-C-A		Tooth agenesis, selective, 9	Pathogenic (Dec 29, 2016)
1-240493213-C-T		not specified	Uncertain significance (Oct 25, 2022)
1-240493226-C-T		not specified	Uncertain significance (Dec 22, 2023)
1-240493238-G-C		Tooth agenesis, selective, 9	Uncertain significance (May 18, 2021)
1-240493250-G-C		Tooth agenesis, selective, 9	Uncertain significance (Oct 13, 2023)
1-240493251-C-T		GREM2-related disorder	Likely benign (Nov 16, 2019)
1-240493298-G-C		not specified	Uncertain significance (May 04, 2022)
1-240493322-C-A		not specified	Uncertain significance (May 11, 2022)
1-240493367-C-T		not specified	Uncertain significance (Mar 14, 2023)
1-240493438-G-A		Tooth agenesis, selective, 9	Pathogenic (May 04, 2022)
1-240493446-G-T		not specified	Uncertain significance (Nov 08, 2022)
1-240493459-G-C		not specified	Uncertain significance (Dec 21, 2023)
1-240493469-A-C		not specified	Uncertain significance (Dec 27, 2022)
1-240509503-T-G		not specified	Benign (Apr 02, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GREM2	protein_coding	protein_coding	ENST00000318160	1	122577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0318	0.827	125617	0	3	125620	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	78	115	0.677	0.00000789	1089
Missense in Polyphen		20	35.743	0.55956		355
Synonymous	1.38	42	55.1	0.763	0.00000403	335
Loss of Function	1.15	3	6.07	0.494	3.11e-7	62

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells. {ECO:0000250|UniProtKB:O88273}.
• Disease: DISEASE: Tooth agenesis, selective, 9 (STHAG9) [MIM:617275]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG9 inheritance is autosomal dominant. {ECO:0000269|PubMed:26416033}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;BMP Signalling Pathway;Signaling by BMP;Signaling by TGF-beta family members (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.368
• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.573
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grem2
• Phenotype: skeleton phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: grem2b
• Affected structure: pharyngeal arch 1
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: embryonic body morphogenesis;cytokine-mediated signaling pathway;BMP signaling pathway;sequestering of BMP from receptor via BMP binding;determination of dorsal identity;regulation of cytokine activity
• Cellular component: extracellular region;extracellular space
• Molecular function: cytokine activity;heparin binding;BMP binding;protein homodimerization activity