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16 Jun 2026	Likely inborn error of metabolism v9.11	FOCAD	Ida Ertmanska Classified gene: FOCAD as Amber List (moderate evidence)
16 Jun 2026	Likely inborn error of metabolism v9.11	FOCAD	Ida Ertmanska Gene: focad has been classified as Amber List (Moderate Evidence).
16 Jun 2026	Likely inborn error of metabolism v9.10	FOCAD	Ida Ertmanska commented on gene: FOCAD: Comment on list classification: There are now numerous individuals reported with biallelic FOCAD variants and severe congenital liver disease. Liver cirrhosis in the neonatal period was a consistent finding. 86% of patients also had metabolic anomalies (e.g., steatosis, increased glycogen content, iron overload). Hence, this gene should be promoted to Green at the next GMS update. This association is tagged for expert review regarding phenotypic fit for the panel, as the metabolic anomalies are quite variable. Inclusion on this panel would also ensure inclusion on R27 Paediatric disorders, which covers more syndromic presentations.
16 Jun 2026	Likely inborn error of metabolism v9.10	FOCAD	Ida Ertmanska changed review comment from: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7%), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature; to: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7% - e.g., steatosis, increased glycogen content, iron overload), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature
16 Jun 2026	Likely inborn error of metabolism v9.10	FOCAD	Ida Ertmanska gene: FOCAD was added gene: FOCAD was added to Likely inborn error of metabolism. Sources: Literature Q2_26_promote_green, Q2_26_expert_review tags were added to gene: FOCAD. Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOCAD were set to 35864190; 40662096; 41189834; 41608453 Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, OMIM:619991; liver disease, severe congenital, MONDO:0859273 Review for gene: FOCAD was set to GREEN Added comment: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7%), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature
11 Feb 2021	Likely inborn error of metabolism v2.71	ACADVL	Eleanor Williams Source: Expert Review Red was removed from gene: ACADVL
11 Feb 2021	Likely inborn error of metabolism v2.70	ACADSB	Eleanor Williams Source: Expert Review Red was removed from gene: ACADSB
11 Feb 2021	Likely inborn error of metabolism v2.69	ACADS	Eleanor Williams Source: Expert Review Red was removed from gene: ACADS
11 Feb 2021	Likely inborn error of metabolism v2.68	ACADM	Eleanor Williams Source: Expert Review Red was removed from gene: ACADM
13 Feb 2019	Likely inborn error of metabolism v1.47	ACADVL	Ivone Leong Source NHS GMS was added to ACADVL. Source London North GLH was added to ACADVL.
13 Feb 2019	Likely inborn error of metabolism v1.47	ACADSB	Ivone Leong Source NHS GMS was added to ACADSB. Source London North GLH was added to ACADSB.
13 Feb 2019	Likely inborn error of metabolism v1.47	ACADS	Ivone Leong Source NHS GMS was added to ACADS. Source London North GLH was added to ACADS.
13 Feb 2019	Likely inborn error of metabolism v1.47	ACADM	Ivone Leong Source NHS GMS was added to ACADM. Source London North GLH was added to ACADM.
13 Feb 2019	Likely inborn error of metabolism v1.47	ACAD9	Ivone Leong Source NHS GMS was added to ACAD9. Source London North GLH was added to ACAD9.
13 Feb 2019	Likely inborn error of metabolism v1.47	ACAD8	Ivone Leong Source NHS GMS was added to ACAD8. Source London North GLH was added to ACAD8.
16 Dec 2018	Likely inborn error of metabolism v0.4	CAD	Ellen McDonagh gene: CAD was added gene: CAD was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CAD were set to ?Congenital disorder of glycosylation, type Iz 616457
16 Dec 2018	Likely inborn error of metabolism v0.4	ACADVL	Ellen McDonagh gene: ACADVL was added gene: ACADVL was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACADVL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADVL were set to 27604308 Phenotypes for gene: ACADVL were set to VLCAD deficiency; Very long - chain acyl CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation)
16 Dec 2018	Likely inborn error of metabolism v0.4	ACADSB	Ellen McDonagh gene: ACADSB was added gene: ACADSB was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACADSB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADSB were set to 27604308 Phenotypes for gene: ACADSB were set to 2-methylbutyrylglycinuria 610006; 2-Methylbutyric aciduria (Organic acidurias)
16 Dec 2018	Likely inborn error of metabolism v0.4	ACADS	Ellen McDonagh gene: ACADS was added gene: ACADS was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACADS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADS were set to 27604308; 24816252 Phenotypes for gene: ACADS were set to Acyl-CoA dehydrogenase, short-chain, deficiency of
16 Dec 2018	Likely inborn error of metabolism v0.4	ACADM	Ellen McDonagh gene: ACADM was added gene: ACADM was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADM were set to 27604308; 24816252 Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of; Medium - chain acyl CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation)
16 Dec 2018	Likely inborn error of metabolism v0.4	ACAD9	Ellen McDonagh Added phenotypes Mitochondrial complex I deficiency due to ACAD9 deficiency; ACAD9 deficiency, 611126; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Isolated complex I deficiency for gene: ACAD9 Publications for gene ACAD9 were changed from PMID:17564966; 21057504 to 27604308
16 Dec 2018	Likely inborn error of metabolism v0.4	ACAD9	Ellen McDonagh gene: ACAD9 was added gene: ACAD9 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACAD9 were set to PMID:17564966; 21057504 Phenotypes for gene: ACAD9 were set to Mitochondrial complex I deficiency due to ACAD9 deficiency; ACAD9 deficiency, 611126; Isolated complex I deficiency
16 Dec 2018	Likely inborn error of metabolism v0.4	ACAD8	Ellen McDonagh gene: ACAD8 was added gene: ACAD8 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ACAD8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACAD8 were set to 27604308 Phenotypes for gene: ACAD8 were set to Isobutyric aciduria (Organic acidurias)