CLPTM1L

Chr 5

CLPTM1 like

Also known as: CRR9

This scramblase mediates the translocation of glucosaminylphosphatidylinositol across the endoplasmic reticulum membrane, participating in the biosynthesis of glycosylphosphatidylinositol (GPI) used for post-translational protein modification. Mutations cause autosomal recessive developmental disorders affecting multiple organ systems. The gene is highly constrained against loss-of-function variants (LOEUF 0.645), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.65
Clinical SummaryCLPTM1L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.000
Z-score 3.12
OE 0.41 (0.260.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.57Z-score
OE missense 0.91 (0.831.00)
301 obs / 330.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.260.65)
00.351.4
Missense OE0.91 (0.831.00)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 13 / 32.0Missense obs/exp: 301 / 330.0Syn Z: -1.52
DN
0.75top 25%
GOF
0.6150th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLPTM1L · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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