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Gene

SMAD4

SMAD family member 4

Summary

Cytogenetic location
18q21.2
Coordinates
Chromosome 18: 51,030,213–51,085,042 (GRCh38)
Exons
12 exons across 54.8 kb
Protein
552 amino acids
Inheritance
Autosomal dominant
Also known as
DPC4
Previous symbols
MADH4
MANE Select transcript
ENST00000342988.8NM_005359.6
Locus type
gene with protein product
  • Very high
  • Confident
  • Low
  • Very low

Reference genomeGRCh38

Positions on gene and variant pages follow this choice, in this browser.

Curated reports relevant to this gene

  • Hereditary Hemorrhagic Telangiectasia

    • Juvenile Polyposis/Hereditary Haemorrhagic Telangiectasia SyndromeAutosomal dominant

      A condition caused by changes in SMAD4 that combines polyps in the digestive tract with the blood vessel abnormalities of hereditary haemorrhagic telangiectasia.

      • ClinGen rates the link definitive
      • 5 GenCC submitters rate it definitive or strong
      • On the ACMG secondary findings list
      What knowing changes

      Knowing about it supports screening for blood vessel malformations in the lungs and brain, and regular bowel and stomach surveillance.

  • Juvenile Polyposis Syndrome

    • Juvenile polyposis/hereditary haemorrhagic telangiectasia syndromeAutosomal dominant

      SMAD4-related juvenile polyposis combined with features of hereditary haemorrhagic telangiectasia, such as nosebleeds and abnormal blood vessels in the lungs, brain or liver.

      • ClinGen rates the link definitive
      • 5 GenCC submitters rate it definitive or strong
      • On the ACMG secondary findings list
      What knowing changes

      In addition to bowel surveillance, screening for arteriovenous malformations in the lungs and brain is recommended.

    • Autosomal dominant

      Multiple hamartomatous (juvenile) polyps of the gastrointestinal tract with an increased risk of colorectal and gastric cancer.

      • 2 GenCC submitters rate it definitive or strong
      • On the ACMG secondary findings list
      What knowing changes

      Regular colonoscopy and upper endoscopy, usually from the early teens, with polyp removal; relatives can be offered testing.

Broader groupings

  • Intellectual Disability

    • One of 233 genes linked to it

      • ClinGen rates the link definitive
      • 4 GenCC submitters rate it definitive or strong

Inheritance

Autosomal dominant
One changed copy, from either parent, is enough. A parent who has one passes it on to each child with a one-in-two chance.

How SMAD4 is laid out

  • Coding sequence
  • Untranslated region
  • Intron
  • Direction of transcription
  • Known disease-causing sites
  • Stretches short reads find hard
  • Variants with a page
Chromosome 18, with a bracket where SMAD4 sits. SMAD4 and 6 genes near it on chromosome 18, from 50,557,628 to 51,557,627.Chromosome 1818q21.2p11.32p11.31p11.23p11.22p11.21p11.1q11.1q11.2q12.1q12.2q12.3q21.1q21.2q21.31q21.32q21.33q22.1q22.2q22.3q2350.6 Mb50.8 Mb51 Mb51.2 Mb51.4 MbMAPK4: 50,559,451–50,731,830, forward strandMAPK4MRO: 50,795,120–50,843,112, reverse strandMROME2: 50,878,664–50,954,257, forward strandME2ELAC1: 50,967,989–51,000,735, forward strandELAC1: 50,968,019–51,058,144, forward strandSMAD4: 51,030,213–51,085,042, forward strandSMAD4MEX3C: 51,174,550–51,218,333, reverse strandMEX3CDiagram of SMAD4: 12 exons on the forward strand of chromosome 18Exon 2: 20 known disease-causing sitesExon 3: 26 known disease-causing sitesExon 4: 3 known disease-causing sitesExon 5: 19 known disease-causing sitesExon 6: 20 known disease-causing sitesExon 7: 19 known disease-causing sitesExon 8: 9 known disease-causing sitesExon 9: 32 known disease-causing sitesExon 10: 28 known disease-causing sitesExon 11: 20 known disease-causing sitesExon 12: 32 known disease-causing sitesExon 1: 51,030,213–51,030,623, 411 basesExon 2: 51,046,920–51,047,295, 376 basesExon 3: 51,048,686–51,048,860, 175 basesExon 4: 51,049,295–51,049,324, 30 basesExon 5: 51,054,781–51,054,993, 213 bases. 1 variant with a page in exon 5. List themExon 6: 51,058,125–51,058,244, 120 basesExon 7: 51,058,340–51,058,456, 117 bases. 1 variant with a page in exon 7. List themExon 8: 51,059,866–51,059,916, 51 basesExon 9: 51,065,423–51,065,606, 184 bases. 6 variants with a page in exon 9. List themExon 10: 51,067,019–51,067,187, 169 bases. 2 variants with a page in exon 10. List themExon 11: 51,076,638–51,076,776, 139 basesExon 12: 51,078,256–51,085,042, 6,787 bases. 4 variants with a page in exon 12. List them1246810125′3′

Exons of the gene's MANE Select transcript (release v1.5), from NCBI and EMBL-EBI, on the GRCh38 reference genome.

Chromosome bands from UCSC's GRCh38 ideogram (2022-10-29).

Nearby genes from Ensembl release 116, on GRCh38.

Exons make up 8.8 kb of the gene's 54.8 kb; 1,659 of those bases code for the protein.

How a genome test reads SMAD4

254

positions in SMAD4 where ClinVar classes a change as pathogenic or likely pathogenic

None of them falls in a region short reads find hard.

A whole genome covers all 54.8 kb of SMAD4, introns included, not only the 8.8 kb of exons.

Variants with a page (15)

The SMAD4 variants with a page here, most review stars first. Each page describes ClinVar's public record of the variant, never a result.

VariantHGVS c.Exon or intronPosition (GRCh38)ClinVar classificationReview status
c.424+1G>AIntron 351,048,861Likely pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
D351Vc.1052A>TExon 951,065,519Likely pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
D415Efs*20c.1245_1248delExon 1051,067,120Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
G299Dfs*37c.894delExon 751,058,443Pathogenic/likely pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
G352Rc.1054G>AExon 951,065,521Pathogenic/likely pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
I500Tc.1499T>CExon 1251,078,307Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
I500Vc.1498A>GExon 1251,078,306Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
P342Lfs*42c.1023delExon 951,065,488Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
R361Cc.1081C>TExon 951,065,548Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts
R361Hc.1082G>AExon 951,065,549Pathogenic2 stars out of 4 criteria provided, multiple submitters, no conflicts

See all 15 SMAD4 variants →

Where this comes from

  • HGNC: the gene's symbol, name, other symbols and location.
  • MANE Select v1.5, from NCBI and EMBL-EBI: the transcript, its exons and coding sequence.
  • GenCC and ClinGen, released 2026-10-16: which conditions the gene is linked to, and how strongly.
  • The ACMG secondary findings list, SF v3.2.
  • ClinVar and the GIAB stratifications: known disease-causing sites, and the regions short reads find hard.
  • The Human Phenotype Ontology, release 2026-09-01: the traits linked to the gene. Find out more at hpo.jax.org.
  • Data release 2026.10.16-c6eea6bf.

Cite this page

APA

Dante Labs. (n.d.). SMAD4 gene: SMAD family member 4. Retrieved 16 October 2026, from https://dantelabs.com/genes/smad4

Vancouver

Dante Labs. SMAD4 gene: SMAD family member 4 [Internet]. [cited 16 October 2026]. Available from: https://dantelabs.com/genes/smad4

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