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Mendeliome v2.208 GPR15 Bryony Thompson Classified gene: GPR15 as Amber List (moderate evidence)
Mendeliome v2.208 GPR15 Bryony Thompson Gene: gpr15 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.207 GPR15 Bryony Thompson gene: GPR15 was added
gene: GPR15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR15 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GPR15 were set to 42259915
Phenotypes for gene: GPR15 were set to inflammatory bowel disease MONDO:0005265
Review for gene: GPR15 was set to AMBER
Added comment: GPR15 encodes a G protein‑coupled receptor that directs CD8⁺ regulatory T cells to the colon. PMID 42259915 reports 2 families with heterozygous truncating variants (p.Q281X, p.Y215X) presenting with early‑onset inflammatory bowel disease (IBD) in a dominant pattern. Affected carriers show variable penetrance (4/10; 40%), with some individuals mildly affected. Functional assays in patient T cells demonstrate reduced GPR15 surface expression, impaired Ca²⁺ signaling and defective chemotaxis, which is rescued by wild‑type GPR15; Gpr15‑null mice develop colitis, supporting a loss‑of‑function mechanism. PMID 42259915 also describes 2 families (1 mentioned above with both monoallelic and biallelic) with biallelic loss‑of‑function variants (compound heterozygous p.D306N/p.Q281X and homozygous p.Y215X) with severe early‑onset IBD (penetrance was partial in biallelic 3/4; 75%). Patient‑cell assays again show defective trafficking and signaling, restored by wild‑type rescue, and mouse models recapitulate colitis. One additional family homozygous for p.Y132S/p.F159I was excluded due to the high population frequency of p.Y132S. Suggested to be a possible hypomorph. Only 3 families contribute assessment, with suggested semidominant incomplete penetrance.
Sources: Literature
Mendeliome v1.1324 GPR156 Zornitza Stark Phenotypes for gene: GPR156 were changed from Sensorineural hearing loss, MONDO:60700002, GPR156-related to Deafness, autosomal recessive 121, MIM# 620551
Mendeliome v1.1323 GPR156 Zornitza Stark reviewed gene: GPR156: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 121, MIM# 620551; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.841 GPR156 Zornitza Stark Marked gene: GPR156 as ready
Mendeliome v1.841 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.841 GPR156 Zornitza Stark Classified gene: GPR156 as Green List (high evidence)
Mendeliome v1.841 GPR156 Zornitza Stark Gene: gpr156 has been classified as Green List (High Evidence).
Mendeliome v1.834 GPR156 Anna Ritchie gene: GPR156 was added
gene: GPR156 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR156 were set to PMID: 36928819
Phenotypes for gene: GPR156 were set to Sensorineural hearing loss, MONDO:60700002, GPR156-related
Review for gene: GPR156 was set to GREEN
Added comment: Eight affected individuals from three unrelated families with congenital nonsyndromic bilateral sensorineural hearing loss. Homozygous or compound heterozygous loss of function variants were reported in these families.
Sources: Literature