LZTFL1

Chr 3AR

leucine zipper transcription factor like 1

Also known as: BBS17

NCBI Gene: 54585ENSG00000163818UniProt: Q9NQ48OMIM: 606568

LZTFL1 encodes a cytoplasmic protein that regulates trafficking of the BBSome protein complex to the ciliary membrane and controls ciliary localization essential for sonic hedgehog signaling. Mutations cause Bardet-Biedl syndrome 17, a ciliopathy presenting with polydactyly, obesity, cognitive impairment, hypogonadism, and progressive kidney failure. This condition follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.571 OMIM phenotype
Clinical Summary— LZTFL1
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Gene-Disease Validity (ClinGen)
LZTFL1-related ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 158 VUS of 305 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — LZTFL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.059
Z-score 2.98
OE 0.29 (0.16–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.65Z-score
OE missense 0.61 (0.52–0.73)
89 obs / 144.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.16–0.57)
0≤0.351.4
Missense OE0.61 (0.52–0.73)
0≤0.61.4
Synonymous OE0.79
0≤1.21.6
LoF obs/exp: 6 / 20.6Missense obs/exp: 89 / 144.9Syn Z: 1.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongLZTFL1-related Bardet-Biedl syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7230th %ile
GOF
0.5856th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

305 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic11
VUS158
Likely Benign102
Benign3
Conflicting3
19
Pathogenic
11
Likely Pathogenic
158
VUS
102
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
1
8
0
19
Likely Pathogenic
8
1
1
1
11
VUS
2
143
12
1
158
Likely Benign
0
6
54
42
102
Benign
0
2
0
1
3
Conflicting
—3
Total201537545296

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

View in ClinVar →

Protein Context — Lollipop Plot

LZTFL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients