BLTP1

Chr 4AR

bridge-like lipid transfer protein family member 1

Also known as: ALKKUCS, FSA, KIAA1109, Tweek

NCBI Gene: 84162 ENSG00000138688 UniProt: Q2LD37 OMIM: 611565

The encoded protein functions as a bridge-like lipid transfer protein that transports phospholipids between the endoplasmic reticulum and target membranes, and is involved in endosomal trafficking, actin cytoskeleton dynamics, and cilia structure. Biallelic mutations cause Alkuraya-Kucinskas syndrome, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.41), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.411 OMIM phenotype

Clinical Summary— BLTP1

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Gene-Disease Validity (ClinGen)

Alkuraya-Kucinskas syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 44 VUS of 99 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.41LOEUF

pLI 0.000

Z-score 9.56

OE 0.34 (0.29–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

6.00Z-score

OE missense 0.67 (0.64–0.69)

1707 obs / 2561.8 exp

Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?

LoF OE?0.34 (0.29–0.41)

0≤0.351.4

Missense OE?0.67 (0.64–0.69)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 84 / 245.8Missense obs/exp: 1707 / 2561.8Syn Z: 1.47

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic3

VUS44

Likely Benign6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	5	0	5
Likely Pathogenic	3	0	3
VUS	0	44	44
Likely Benign	0	6	6
Benign	0	0	0
Total	8	50	58

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

1 pathogenic / likely-pathogenic (of 1) ClinVar copy-number / structural variants overlap BLTP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →