CERS6

Chr 2

ceramide synthase 6

Also known as: LASS6

NCBI Gene: 253782 ENSG00000172292 UniProt: Q6ZMG9 OMIM: 615336

Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.51

Clinical Summary— CERS6

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

37 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.039

Z-score 3.53

OE 0.28 (0.17–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.66Z-score

OE missense 0.87 (0.78–0.99)

191 obs / 218.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.17–0.51)

0≤0.351.4

Missense OE?0.87 (0.78–0.99)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 28.2Missense obs/exp: 191 / 218.3Syn Z: -0.44

This gene — mechanism propensity

0.7035th %ile

GOF

0.6735th %ile

LOF

0.2970th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign5

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	37	0	37
Likely Benign	3	2	5
Benign	1	1	2
Total	41	3	44

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap CERS6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →