Autoinflammatory disorders

Gene: RIPK1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 2:17 p.m. | Last Modified: 10 Dec 2025, 2:17 p.m.

Panel Version: 2.34

Comment on list classification: As reviewed by Dorota Rowczenio, there is sufficient evidence available for the association of both monoallelic and biallelic variants in RIPK1 gene with autoinflammatory disease phenotypes (MIMs #618852 & 618108). Hence, this gene can be promoted to green rating in the next GMS update.

Created: 16 Jun 2025, 1:20 p.m. | Last Modified: 16 Jun 2025, 1:20 p.m.

Panel Version: 2.29

PMID:30026316 - Four patients from three unrelated families identified with rare homozygous loss-of-function deletion variants in the RIPK1 gene. They presented with recurrent infections, early-onset inflammatory bowel disease and progressive polyarthritis, showing that they had both immunodeficiency and autoinflammation. There is also supporting functional evidence available.

PMID:31827280 - Four members of a family and an unrelated boy were reported with heterozygous RIPK1 variants affecting the same residue (p.Asp324His & p.Asp324Val) and with distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Functional evidence is available.

PMID:31827281 - Seven patients from three unrelated families were identified with heterozygous RIPK1 variants affecting the same residue as patients from PMID:31827280 (p.Asp324Asn, p.Asp324His & p.Asp324Tyr) and they all presented with an autoinflammatory disorder (AID) characterised by fevers and pronounced lymphadenopathy beginning in early childhood and continuing throughout adulthood. Functional evidence and mouse model available.

PMID:35716229 - Three unrelated families with early-onset AID were identified with two novel missense RIPK1 variants (p.Leu321Arg & p.Asp324Gly). Functional evidence available for these variants.

PMID:37452601 - A family with three generations were reported with AID and with heterozygous RIPK1 variant (p.Asp324His).

Created: 16 Jun 2025, 1:16 p.m. | Last Modified: 16 Jun 2025, 1:16 p.m.

Panel Version: 2.26

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation with episodic fever and lymphadenopathy, OMIM:618852; Immunodeficiency 57 with autoinflammation, OMIM: 618108

Publications

• 30026316
• 31827280
• 31827281
• 31911632
• 35716229
• 35786329
• 39557292

Green List (high evidence)

Sources: Expert list, Expert Review, Literature, Research

Created: 4 Jun 2025, 4:37 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation with episodic fever and lymphadenopathy (autosomal dominant); Immunodeficiency 57 with autoinflammation (autosomal recessive)

Publications

• PMID: 31911632
• PMID: 31827281
• PMID:31827280
• PMID: 39557292
• PMID: 37452601
• PMID:35716229
• PMID:35786329