SMAD4

SMAD family member 4

10 disorders 7 untyped 1 causative 1 somatic driver 1 no genetic record 18q21.2 gene with protein product

HGNC:6770 Monarch NCBI Gene 4089 ENSG00000141646 UniProt Q13485 OMIM 600993

Previous symbols: MADH4. Aliases: DPC4.

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Gastric Adenocarcinoma	causative germline	mechanism: Gastric Dysplasia
Pseudomyxoma Peritonei	somatic driver somatic
Esophageal Adenocarcinoma	untyped Recurrent Somatic Alteration
Gallbladder Cancer	untyped Somatic Loss-of-Function Mutation
Hereditary Hemorrhagic Telangiectasia	untyped Pathogenic Mutations	subtype: SMAD4-associated juvenile polyposis/HHT overlap scoped to subtype: SMAD4-associated juvenile polyposis/HHT overlap
Juvenile Polyposis Syndrome	untyped Causative	mechanism: Germline SMAD4 loss-of-function predisposition diagnosis: Molecular genetic testing for BMPR1A and SMAD4
Myhre Syndrome	untyped Causative
Pancreatic Ductal Adenocarcinoma	untyped Somatic Loss-of-Function Mutation
Pancreatic Mucinous Cystadenoma	untyped PREDISPOSING
Small Intestine Cancer	no genetic record	mechanism: Adenoma-Carcinoma Sequence and Wnt-APC Activation subtype: Adenocarcinoma

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Myhre syndrome MONDO:0007688	AD	Definitive 2025-10-29	Myhre Syndrome untyped
juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MONDO:0008278	AD	Definitive 2023-04-18	Hereditary Hemorrhagic Telangiectasia untyped
pulmonary arterial hypertension MONDO:0015924	AD	Disputed 2022-11-21	Pulmonary_hypertension not named

Mechanism modules · computed from kb/

germline_two_hit_tumor_predisposition via Juvenile Polyposis Syndrome

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.