GREM1

Chr 15

gremlin 1, DAN family BMP antagonist

Also known as: C15DUPq, CKTSF1B1, CRAC1, CRCS4, DAND2, DRM, DUP15q, GREMLIN

NCBI Gene: 26585 ENSG00000166923 UniProt: O60565

This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPolyposis syndrome, mixed hereditary 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hereditary mixed polyposis syndrome · AD · ClinGen 2022

Active trials

100

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

—

Mechanism

📖

GeneReview available — GREM1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GREM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 550

197 rare PASS variants

Rare truncating (LoF)

1 in 13,000

21 rare PASS variants

Rare synonymous (reference)

1 in 1,000

97 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GREM1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 610	1 in 10,000
South Asian	~43k	1 in 750	none seen
Remaining (unassigned)	~30k	1 in 650	≈ 1 in 7,300
European (Finnish)	~27k	1 in 830	≈ 1 in 13,000
Admixed American	~22k	1 in 390	≈ 1 in 22,000
African / African American	~21k	1 in 380	≈ 1 in 17,000
East Asian	~20k	1 in 510	none seen
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GREM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — GREM1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Familial Adenomatous Polyposis (FAP)Attenuated Familial Adenomatous Polyposis (AFAP)MUTYH-Associated Polyposis (MAP)

Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)

ACTIVE NOT RECRUITING

NCT07461246Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoStarted 2024-05-13

BRCA1 MutationPOLD1 Gene MutationCDKN2A Mutation

An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results

RECRUITING

NCT05420064Phase NAMemorial Sloan Kettering Cancer CenterStarted 2022-12-01

Intervention Arm At-risk Relative/ARR ContactsMyGene PortalStandard of Care

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

GREM1 signaling in cancer: tumor promotor and suppressor?

Gao Z et al.·J Cell Commun Signal

2023