biostudies-literatureKohler JNNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteNHGRI NIH HHSNational Cancer InstituteNational Institute of Mental HealthNINDS NIH HHSNational Institutes of HealthNational Human Genome Research InstituteNational Institute on Drug Abuse101166https://www.ebi.ac.uk/biostudies/studies/S-EPMC11451386biostudies-literatureUnknown26(9)<h4>Purpose</h4>The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in 4 siblings.<h4>Methods</h4>We identified 5 individuals from 3 unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort.<h4>Results</h4>These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the GolGenetics in medicine : official journal of the American College of Medical GeneticsLoss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder.PMC11451386U01HG010218F32 HG000130U01 HG010218U01 NS134358Dasari SUndiagnosed Diseases NetworkLiu XZEmrick LTWener MNovacic DMalicdan MCVWorley KSutton SCunningham MAmendola LButte MJJobanputra VWalker MStoler JMEzell KDickson PJean-Marie OLawrence Merritt JBonner DKozuira MLoo SKSmith ECSeto EHahn SCoakley TRFeng WFieg ELPapp JCBellen HJAcosta MTSessions Cole FHolt JMMontgomery SBChang TCPPosey JELanza IRSilverman EKForghani IDayal JGJarvik GPVogel TPAdams DRKrakow DByers PMartin MGFisher PGBale JFogel BLMaghiro AMahoney RRenteria GSinsheimer JSLanpher BCIzumi KScott DAMcCray ATPhillips JAWhitlock JNewman JHSweetser DAAdam MMcAdow ARGoddard PAlvey JTran AAGochuico BMacnamara EFCarrasquillo OBowman ACobban LANickerson DBerg-Rood BRaper ADavis JTarakad AMarth GCogan JDSchaechter JNicholas SKBivona STabor HKWenger TPusey Swerdzewski BNBejerano GMulvihill JJarvik JCraigen WJMight MBoyd BIsasi RLegro NRJackstadt MMWangler MFKaraviti LPak SZuchner SBayrak-Toydemir PHisama FMMartin BAHayes NLongo NKetkar SRosenfeld JAJamal FMao RLiu PSullivan KMamounas LAWallace SWambach JAlvarez RLLalani SRDorrani NParker NHBlue EJensen TAlvarez RPalmer CGSSaporta MOrengo JPThorson WWheeler MTTelischi FHing AHorike-Pyne MMartinez-Agosto JABennett JKilich GBamshad MCorona RZhang ZTekin MEng CMD'Souza PHom JShriver LPKravets EFresard LCarl Pallais JNelson SFSmith KSHalley MCSybert VIntrone WKrasnewich DMBohnsack JUrv TKTifft CJWan JBaldridge DLewis RAZhang BHolm IASacco RSolomon BSolnica-Krezel LClark GDMcCauley JRodan LHByrd WEKohane ISNieves-Rodriguez SBeck AMoretti PPotocki LGrajewski ACrouse ABGlass IWegner DDoss ALRon Scott CHutchison SRives LCoggins MAndrews AKiley DKohler JNShashi VBehrens ETan ALMBotto LAshley EABacino CAChanprasert SEckstein DJBarbouth DBriere LCQuinlan ARuzhnikov MMaravilla KBeggs AHMarwaha SNakano-Okuno MHamid RReuter CMXiao CDai HSpillmann RCGoddard PCSisco KSun AVanderver AShin JBalasubramanyam ABurrage LCSchoch KMarom RUngar RAManolio TAToro CPace LLee BHCassini TChao HTHuang AOglesbee DVelinder MYang JWorthey EAMcConkie-Rosell AMorava EMaduro VVYamamoto SViskochil DCarey JSampson JBLevitt RBademci GFalk MHigh FBernstein JAPostlethwait JBerry GTBican ABurke EAKobren SNLam BLeBlanc KMcCormack CLam CRossignol FWalley NMRobertson AKHassey KCope HWard PAEarl DMcGee EPatti GJMacRae CAHubshman MWMefford HChinn ISullivan JADoherty DMirzaa GUgur BCorner BRosenwasser NMaas RLColley HAGahl WALoscalzo JSchedl TJayadev SRao DADe Camilli PHadley DDipple KNeumann SWolfe LAKorrick SRaskind WDell'Angelica ECGodfrey RATan QKWesterfield MDouine EDWahl CEGolden-Grant KfalseLoss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder.<h4>Purpose</h4>The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in 4 siblings.<h4>Methods</h4>We identified 5 individuals from 3 unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort.<h4>Results</h4>These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the Gol2024-01-01T00:00:00Z2024 Sep2026-05-29T09:33:34.581Z2026-04-08T04:12:44.047ZS-EPMC114513863876705910.1016/j.gim.2024.101166