CASD1

Chr 7

CAS1 domain sialic acid O acetyltransferase 1

Also known as: C7orf12, Cas1, Cas1p, NBLA04196, SOAT

NCBI Gene: 64921 ENSG00000127995 UniProt: Q96PB1

CASD1 encodes an N-acetylneuraminate 9-O-acetyltransferase that catalyzes the biosynthesis of O-acetylated sialoglycans including gangliosides O-AcGD3 and O-AcGD2, which are critical for cell-cell interactions and neural function. The gene is highly constrained against loss-of-function variants (LOEUF 0.435), suggesting mutations would be deleterious, though no specific human disease phenotype has been established yet. Any associated disorder would likely follow autosomal recessive inheritance given the gene's tolerance to heterozygous loss-of-function.

ResearchSummary from RefSeq, UniProt

Enables N-acetylneuraminate 9-O-acetyltransferase activity. Involved in carbohydrate metabolic process. Located in Golgi membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.43

Clinical Summary— CASD1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

158 unique Pathogenic / Likely Pathogenic· 385 VUS of 793 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

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.045

Z-score 4.42

OE 0.26 (0.16–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.96Z-score

OE missense 0.73 (0.66–0.80)

294 obs / 405.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.16–0.43)

0≤0.351.4

Missense OE?0.73 (0.66–0.80)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 11 / 41.9Missense obs/exp: 294 / 405.3Syn Z: 0.21

This gene — mechanism propensity

0.6550th %ile

GOF

0.5268th %ile

LOF

0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-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

LOF87% of P/LP variants are LoF · LOEUF 0.43

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

793 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic120

Likely Pathogenic38

VUS385

Likely Benign171

Benign26

Conflicting20

120

Pathogenic

Likely Pathogenic

385

VUS

171

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	111	4	5	0	120
Likely Pathogenic	27	9	2	0	38
VUS	8	346	26	5	385
Likely Benign	0	4	83	84	171
Benign	0	3	21	2	26
Conflicting	—				20
Total	146	366	137	91	760

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap CASD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →