ABHD11

Chr 7

abhydrolase domain containing 11

Also known as: PP1226, WBSCR21

NCBI Gene: 83451 ENSG00000106077 UniProt: Q8NFV4

The protein catalyzes the hydrolysis of diacylglycerol to regulate lipid metabolism and maintains functional lipoylation of the 2-oxoglutarate dehydrogenase complex. ABHD11 is deleted in Williams syndrome, a multisystem developmental disorder caused by contiguous gene deletions at 7q11.23, with autosomal dominant inheritance. The gene shows low constraint against loss-of-function variants (pLI 0.003), suggesting that isolated ABHD11 mutations may not cause significant disease phenotypes.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing an alpha/beta hydrolase fold domain. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.94

Clinical Summary— ABHD11

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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

60 VUS of 75 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?

0.94LOEUF

pLI 0.003

Z-score 1.72

OE 0.48 (0.26–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.57Z-score

OE missense 0.89 (0.78–1.00)

176 obs / 198.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.26–0.94)

0≤0.351.4

Missense OE?0.89 (0.78–1.00)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 6 / 12.6Missense obs/exp: 176 / 198.5Syn Z: -0.14

This gene — mechanism propensity

0.79top 25%

GOF

0.5660th %ile

LOF

0.2288th %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

75 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	59	1	0	60
Likely Benign	1	3	0	1	5
Benign	0	0	0	0	0
Total	1	62	1	1	65

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

View in ClinVar →

165 pathogenic / likely-pathogenic (of 170) ClinVar copy-number / structural variants overlap ABHD11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →