HHATL

Chr 3

hedgehog acyltransferase like

Also known as: C3orf3, GUP1, MBOAT3, MG56, MSTP002, OACT3

NCBI Gene: 57467ENSG00000010282UniProt: Q9HCP6OMIM: 608116

The protein negatively regulates N-terminal palmitoylation of Sonic Hedgehog (SHH) by counteracting HHAT/SKN activity in the perinuclear cytoplasm. Mutations cause autosomal recessive disorders affecting development, though the gene shows tolerance to loss-of-function variants with a low constraint score. The clinical phenotype and age of onset associated with HHATL mutations require further characterization.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical Summary— HHATL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 79 VUS of 98 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.01
OE 0.58 (0.38–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.91 (0.82–1.00)
275 obs / 302.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.38–0.89)
0≤0.351.4
Missense OE0.91 (0.82–1.00)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 15 / 26.1Missense obs/exp: 275 / 302.2Syn Z: 1.29
DN
0.7227th %ile
GOF
0.78top 25%
LOF
0.2386th %ile

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

GOFprediction above median
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

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS79
Likely Benign1
6
Pathogenic
1
Likely Pathogenic
79
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
1
77
1
0
79
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total1788087

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

View in ClinVar →

Protein Context — Lollipop Plot

HHATL · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients