AP4M1

Chr 7AR

adaptor related protein complex 4 subunit mu 1

Also known as: CPSQ3, MU-4, MU-ARP2, SPG50

NCBI Gene: 9179ENSG00000221838UniProt: O00189OMIM: 602296

This protein is a subunit of the AP-4 complex that recognizes and sorts cargo proteins with tyrosine-based motifs from the trans-Golgi network to the endosomal-lysosomal system. Mutations cause spastic paraplegia 50, an autosomal recessive disorder. The pathogenic mechanism involves disrupted intracellular protein trafficking between these membrane compartments.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.311 OMIM phenotype
Clinical Summary— AP4M1
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Gene-Disease Validity (ClinGen)
AP-4 deficiency syndrome · 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
60 unique Pathogenic / Likely Pathogenic· 220 VUS of 500 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — AP4M1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.26
OE 0.95 (0.69–1.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.21Z-score
OE missense 1.21 (1.10–1.33)
311 obs / 256.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.95 (0.69–1.31)
0≤0.351.4
Missense OE1.21 (1.10–1.33)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 26 / 27.5Missense obs/exp: 311 / 256.4Syn Z: -3.23

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic28
VUS220
Likely Benign169
Benign25
Conflicting5
32
Pathogenic
28
Likely Pathogenic
220
VUS
169
Likely Benign
25
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
1
11
0
32
Likely Pathogenic
24
1
3
0
28
VUS
5
195
17
3
220
Likely Benign
2
3
80
84
169
Benign
0
1
23
1
25
Conflicting
—5
Total5120113488479

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

View in ClinVar →

Protein Context — Lollipop Plot

AP4M1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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