HACD1

Chr 10AR

3-hydroxyacyl-CoA dehydratase 1

Also known as: CAP, CMYO11, CMYP11, MYONP, PTPLA

NCBI Gene: 9200 ENSG00000165996 UniProt: B0YJ81 OMIM: 610467

HACD1 encodes an endoplasmic reticulum enzyme that catalyzes the dehydration step in the elongation cycle of long-chain and very long-chain fatty acids, which serve as precursors for membrane lipids and lipid mediators. Biallelic mutations cause congenital myopathy 11, an autosomal recessive disorder affecting skeletal muscle from birth. The gene shows low constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from OMIM, UniProt

The protein encoded by this gene contains a characteristic catalytic motif of the protein tyrosine phosphatases (PTPs) family. The PTP motif of this protein has the highly conserved arginine residue replaced by a proline residue; thus it may represent a distinct class of PTPs. Members of the PTP family are known to be signaling molecules that regulate a variety of cellular processes. This gene was preferentially expressed in both adult and fetal heart. A much lower expression level was detected in skeletal and smooth muscle tissues, and no expression was observed in other tissues. The tissue specific expression in the developing and adult heart suggests a role in regulating cardiac development and differentiation. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.701 OMIM phenotype

Clinical Summary— HACD1

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Gene-Disease Validity (ClinGen)

congenital myopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

18 unique Pathogenic / Likely Pathogenic· 82 VUS of 194 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?

1.70LOEUF

pLI 0.000

Z-score -0.31

OE 1.10 (0.71–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.87 (0.75–1.02)

114 obs / 130.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.10 (0.71–1.70)

0≤0.351.4

Missense OE?0.87 (0.75–1.02)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 13 / 11.8Missense obs/exp: 114 / 130.4Syn Z: 0.83

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveHACD1-related congenital myopathyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6745th %ile

GOF

0.6834th %ile

LOF

0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

194 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic3

VUS82

Likely Benign67

Benign21

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	4	0	15
Likely Pathogenic	3	0	0	0	3
VUS	2	73	5	2	82
Likely Benign	0	3	31	33	67
Benign	0	6	12	3	21
Conflicting	—				1
Total	16	82	52	38	189

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap HACD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →