ACADM

Chr 1AR

acyl-CoA dehydrogenase medium chain

Also known as: ACAD1, MCAD, MCADH

The encoded protein functions as a mitochondrial acyl-CoA dehydrogenase that catalyzes the initial step of medium-chain fatty acid beta-oxidation (C4-C12). Biallelic mutations cause medium-chain acyl-CoA dehydrogenase deficiency, an autosomal recessive disorder characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy that can result in infantile death. The pathogenic mechanism involves loss of enzymatic function leading to impaired fatty acid oxidation.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Acyl-CoA dehydrogenase, medium chain, deficiency ofMIM #201450
AR
0
Active trials
51
Pubs (1 yr)
235
P/LP submissions
26%
P/LP missense
1.15
LOEUF
LOF
Mechanism· G2P
Clinical SummaryACADM
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Gene-Disease Validity (ClinGen)
medium chain acyl-CoA dehydrogenase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
164 unique Pathogenic / Likely Pathogenic· 159 VUS of 500 total submissions
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GeneReview available — ACADM
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 0.95
OE 0.80 (0.571.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.54Z-score
OE missense 0.90 (0.801.01)
205 obs / 228.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.80 (0.571.15)
00.351.4
Missense OE0.90 (0.801.01)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 21 / 26.2Missense obs/exp: 205 / 228.1Syn Z: 0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveACADM-related medium chain acyl-CoA dehydrogenase deficiencyLOFAR

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

DN
0.7326th %ile
GOF
0.6931th %ile
LOF
0.3453th %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

500 submitted variants in ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic101
VUS159
Likely Benign139
Benign8
Conflicting19
63
Pathogenic
101
Likely Pathogenic
159
VUS
139
Likely Benign
8
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
8
34
0
63
Likely Pathogenic
47
35
19
0
101
VUS
4
107
38
10
159
Likely Benign
0
3
91
45
139
Benign
0
0
7
1
8
Conflicting
19
Total7215318956489

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

View in ClinVar →

Protein Context — Lollipop Plot

ACADM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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