BLTP1

protein-coding

bridge-like lipid transfer protein family member 1, the group of bridge-like lipid transfer protein family

Gene summary

This gene is located on the long arm of chromosome 4 in a region that is associated with susceptibility to celiac disease. The encoded protein is similar to a Chinese hamster protein that is associated with spermatocyte and adipocyte differentiation. The C-terminus of the protein is also similar to a Caenorhabditis elegans protein that plays a role in lipid storage. In mammals, this protein is thought to function in the regulation of epithelial growth and differentiation, and in tumor development. [provided by RefSeq, Oct 2009]

Previous symbols:

KIAA1109

MANE transcript

NM_001384125.1

Inheritance

ClinVar variants

P:65U:598B:128

Top phenotype

Alkuraya-Kucinskas syndrome

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr4:122,152,331-122,364,167

External References & Databases

Ensembl (ENSG00000138688)

Transcript & Mutation Effects

hg38 • Region Span ~211.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Alkuraya-Kucinskas syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0060631

Submitter: ClinGen

BLTP1 (historically KIAA1109) is a non-vesicular lipid transport protein involved in transfer of phospholipids between organelle membranes, with critical roles in synaptic vesicle recycling at the neuromuscular junction [PMID:19640479, 40973493]. Biallelic pathogenic variants in BLTP1 are associated with autosomal recessive Alkuraya-Kucinskas syndrome (MIM#617822; MONDO:0060631), first reported in a neonate with hydrocephalus, pleural effusions, arthrogryposis multiplex congenita, micrognathia and neonatal death by Alazami, 2015 [PMID:25558065]. Since its initial report more than 20 probands with biallelic variants in BLTP1 have been reported, some of which segregated with disease in affected individuals [PMID:25558065, 29290337, 30221345, 30906834, 32657846, 38278647, 40206966], with reported variants including missense, nonsense, frameshift, canonical splice, and multi-exon deletions reported, and maximum points for genetic evidence (12pts) has been reached for this curation. The mechanism of BLTP1-assocaited disorder is proposed to be loss of function, and while there is not a definitive genotype-phenotype correlation both the age of lethality and phenotypic severity are loosely associated to variant severity, with biallelic loss of function (nonsense, frameshift) most often associated with fetal demise or neonatal lethality. Phenotypes in individuals with Alkuraya-Kucinskas syndrome include prenatal findings of arthrogryposis and variable brain malformations including hydrocephalus, ventriculomegaly, vermian atrophy, reduced white matter, neuronal migration or gyral defects, anomalies of the pons, cerebellum and brainstem, and agenesis or hypoplasia of the corpus callosum. Other prenatal findings reported in a subset of affected individuals include cystic hygroma, micrognathia, pleural effusion, and hydrops fetalis. Neonatal respiratory insufficiency and neonatal death are common in severely affected individuals with developmental delay, intellectual disability, progressive development of contractures with age, seizures, and hypotonia observed in those surviving the neonatal period [PMID:25558065, 29290337, 30221345, 30906834, 32657846, 38278647, 40206966]. Functional evidence including multiple non-animal model organisms support the role of loss of BLTP1 in association with Alkuraya-Kucinskas syndrome (MIM#617822; MONDO: 0060631), and have been scored for an additional 2.5 points. Given this and its replication in literature over time, the association with BLTP1 (formerly KIAA1109) with Alkuraya-Kucinskas syndrome is curated as Definitive by the Prenatal Gene Curation Expert Panel (Gene-Disease Validity SOPv11) on January 21, 2026.