CLPTM1L

Chr 5

CLPTM1 like

Also known as: CRR9

NCBI Gene: 81037 ENSG00000049656 UniProt: Q96KA5

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers. [provided by RefSeq, Nov 2015]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.65

Clinical Summary— CLPTM1L

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 84 VUS of 146 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.12

OE 0.41 (0.26–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.57Z-score

OE missense 0.91 (0.83–1.00)

301 obs / 330.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.26–0.65)

0≤0.351.4

Missense OE?0.91 (0.83–1.00)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 13 / 32.0Missense obs/exp: 301 / 330.0Syn Z: -1.52

This gene — mechanism propensity

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

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS84

Likely Benign17

Benign8

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	82	2	0	84
Likely Benign	5	4	8	17
Benign	2	1	5	8
Total	89	8	13	110

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

View in ClinVar →

136 pathogenic / likely-pathogenic (of 152) ClinVar copy-number / structural variants overlap CLPTM1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →